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					HISTORY OF MEDICINE




    TARGET HEALTH INC.
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     WWW.TARGETHEALTH.COM
      julesmitchel@targethealth.com



              30 July 2006
                                                    Table of Contents


1.      ALTERNATIVE MEDICINE .................................................................................... 10
     1.1.     BALANCE OF MIND AND BODY ............................................................................. 10
     1.2.     CACAO USE IN MEDICINE (16TH CENTURY)........................................................... 10
     1.3.     GLASS ARMONICA AND HEALING (1761).............................................................. 11
     1.4.     LEECHES (MIDDLE AGES)................................................................................... 11
     1.5.     LICORICE (220 B.C. – PRESENT) ....................................................................... 11
     1.6.     NIGHTSHADE (19TH CENTURY) ............................................................................ 12
     1.7.     PSYCHOSOMATIC MEDICINE (10TH – 15TH CENTURIES).......................................... 12
     1.8.     SOZODONT POWDER DENTIFRICE AND MRS. WINSLOW'S SOOTHING SYRUP .......... 12
2.      ANCIENT EGYPT .................................................................................................. 13
     2.1.     MEDICINAL PLANTS ........................................................................................... 13
     2.2.     MUMMIFICATION (HERODOTUS 450 B.C.E.) ........................................................ 13
     2.3.     MEDICINE (2600 B.C.E.) ................................................................................... 13
     2.4.     POLIOMYELITIS (POLIO) IN ANCIENT EGYPT ......................................................... 14
     2.5.     SCHISTOSOMIASIS (BILHARZIASIS) IN ANCIENT EGYPT .......................................... 14
     2.6.     TUBERCULOSIS ................................................................................................. 14
3.      ANCIENT GREECE ............................................................................................... 15
     3.1. MEDICINE ......................................................................................................... 15
     3.2. REMEDIES ........................................................................................................ 15
     3.3. ARISTOTLE (384 - 322 B.C.E.) .......................................................................... 16
     3.4. CULT OF ASCLEPIUS (6TH CENTURY B.C.E.) ........................................................ 16
     3.5. CHIRON - THE INVENTOR OF MEDICINE ............................................................... 16
     3.6. DIOSCORIDES OF ANAZARBUS- FATHER OF PHARMACOLOGY (40-90 C.E.)............ 17
     3.7. ERASISTRATUS OF CHIROS (304 - 250 B.C.E.) ................................................... 17
     3.8. GALEN (131 – 201 C.E..................................................................................... 17
       3.8.1. Report 1 ................................................................................................... 17
       3.8.2. Report 2 ................................................................................................... 18
       3.8.3. Report 3 ................................................................................................... 18
     3.9. HIPPOCRATES (5TH CENTURY B.C.E.) ................................................................. 18
       3.9.1. Topic 1 ..................................................................................................... 18
       3.9.2. Topic 2 ..................................................................................................... 19
     3.10.   PLATO AND DIET (5TH-4TH CENTURY B.C.E.)................................................... 19
4.      ANCIENT ROME.................................................................................................... 19
     4.1.     CAESAREAN SECTION ........................................................................................ 19
     4.2.     OPHTHALMOLOGY IN ANCIENT ROME .................................................................. 20
     4.3.     A GLADIATOR'S BLOOD AS A CURE FOR EPILEPSY ............................................... 20
5.      ANCIENT WORLD ................................................................................................. 21
     5.1.     BIRTH CONTROL IN THE ANCIENT WORLD ............................................................ 21
     5.2.     DISEASES ......................................................................................................... 21
     5.3.     GASES ............................................................................................................. 21


                                                                 2
     5.4.      HISTORY ........................................................................................................... 22
     5.5.      DEFORMITY IN THE “BOXING BOYS” .................................................................... 22
     5.6.      GENES AND ARCHEOLOGY - A DIFFERENT KIND OF HISTORY ............................... 22
     5.7.      PRACTITIONERS OF MEDICINE (2100 B.C.E.) ...................................................... 23
6.      ARTS AND DISEASE ............................................................................................ 23
     6.1.      DANTE AND MELANCHOLY (1265 –1321) ............................................................ 23
     6.2.      I GOT RHYTHM: GEORGE GERSHWIN AND BIRTH CONTROL IN THE 1930S ............. 23
     6.3.      PEARL BUCK AND PKU (1921 – 1960)............................................................... 24
     6.4.      VINCENT VAN GOGH (1853-1890) ..................................................................... 24
     6.5.      ROBERT LOUIS STEVENSON (1850 –1894) - HEREDITARY HEMORRHAGIC
               TELANGIECTASIA ............................................................................................... 24
     6.6.      SLEEP APNEA - LEWIS CARROLL AND WILLIAM SHAKESPEARE .............................. 25
7.      BASIC SCIENCE ................................................................................................... 25
     7.1.      GOLGI AND NEUROPSYCHIATRY (19TH CENTURY) ................................................. 25
     7.2.      ROBERT HOOKE (1635 – 1703) ......................................................................... 25
     7.3.      ANTON VAN LEEUWENHOEK (1632-1723) ........................................................... 26
8.      CARDIOLOGY ....................................................................................................... 26
     8.1.      DIURETIC PROPERTIES OF MERCURY (19TH CENTURY) ......................................... 26
     8.2.      TETRALOGY OF FALLOT (1673) .......................................................................... 26
     8.3.      WILLIAM HARVEY (1578 – 1657) - CARDIAC OUTPUT AND THE HOUR GLASS ........ 27
     8.4.      WILLIAM SENHOUSE KIRKES (1822-1864) - PATHOGENESIS OF HYPERTENSION .... 27
     8.5.      RUDOLPH MATAS (1860-1957)– VASCULAR SURGEON ........................................ 28
     8.6.      WOLDEMAR MOBITZ (1924) - 2ND DEGREE ATRIOVENTRICULAR BLOCK ................. 28
     8.7.      JEAN-BAPTISTE DE SENAC (1693-1770) – ARTERIAL PULSE ................................ 28
     8.8.      WILLIAM WITHERING AND THE DISCOVERY OF DIGITALIS (1775)............................ 29
9.      DENTISTRY........................................................................................................... 29
     9.1. ETRUSCAN DENTISTRY (700 B.C.E.) .................................................................. 29
     9.2. JAW FRACTURES (1863).................................................................................... 30
     9.3. NECROTIZING ULCERATIVE STOMATITIS (NOMA) (16TH – 17TH CENTURIES) ............ 30
     9.4. ORAL DISEASE (25,000 YEARS AGO) .................................................................. 30
     9.5. PERIODONTAL DISEASE ..................................................................................... 31
       9.5.1. Bartolomeo Eustachio (1520-1574) ......................................................... 31
       9.5.2. History...................................................................................................... 31
     9.6. TOOTH CARE (5000 B.C.E. – 1000 C.E.) .......................................................... 31
     9.7. TOOTHWORM .................................................................................................... 32
10.         DERMATOLOGY................................................................................................ 32
     10.1.        JOSEPH PLENCK (1735-1807)........................................................................ 32
11.         DISCOVERIES ................................................................................................... 32
     11.1.        THE FIRST ISOLATED ANTIBIOTIC..................................................................... 32
     11.2.        ASPIRIN (ANCIENT ASSYRIA TO 1892) ............................................................. 33
     11.3.        CELSIUS THERMOMETER SCALE (1742)........................................................... 33


                                                                  3
  11.4.    CHEMISTRY AND MEDICINE (19TH CENTURY) .................................................... 34
  11.5.    CYTOPATHOLOGY (20TH CENTURY).................................................................. 34
  11.6.    DEBRIDEMENT (18TH CENTURY TO PRESENT) ................................................... 34
  11.7.    FEVER (17TH AND 18TH CENTURIES) .............................................................. 35
  11.8.    HANDWASHING AS PREVENTATIVE MEDICINE (19TH CENTURY) .......................... 35
  11.9.    OPIOIDS ........................................................................................................ 36
    11.9.1.    History of Opium .................................................................................. 36
    11.9.2.    Heroin and Other Opium Alkaloids (1898)............................................ 36
  11.10. LIPIDS (1824)................................................................................................ 37
  11.11. NITROGLYCERIN AND NITRIC OXIDE (19TH CENTURY) ........................................ 37
  11.12. PENICILLIN (1928) ......................................................................................... 37
  11.13. SHOE FITTING FLUOROSCOPE (1920 –1950)................................................... 38
  11.14. X-RAYS (1895) ............................................................................................. 38
12.     DISEASES.......................................................................................................... 38
  12.1.   DIABETES (1674)........................................................................................... 38
  12.2.   DWARFISM ANCIENT EGYPT (5TH DYNASTY) ..................................................... 39
  12.3.   CHILDBIRTH AND ANESTHESIA - PAIN OR TOIL (1846) ....................................... 39
  12.4.   CANCER (ANCIENT EGYPT TO PRESENT) ......................................................... 39
  12.5.   CUSHING'S DISEASE (1912) ........................................................................... 40
  12.6.   DEAFNESS, ASYLUMS AND EDUCATION (19TH CENTURY) ................................... 40
  12.7.   DUCHENNE MUSCULAR DYSTROPHY (1806 - 1875) ......................................... 40
  12.8.   DISEASES OF THE EAR (324-1453 C.E.) ......................................................... 40
  12.9.   ECLAMPSIA (ANCIENT GREECE TO PRESENT)................................................... 41
  12.10. GLANDULAR THERAPY (19TH CENTURY) ........................................................... 41
  12.11. HEART .......................................................................................................... 41
    12.11.1. History .................................................................................................. 42
    12.11.2. Heart Disease (20th Century)................................................................ 42
  12.12. JAUNDICE (NEONATAL) (1785 – PRESENT)...................................................... 42
  12.13. MACULAR EDEMA (1856 – 1950) ................................................................... 43
  12.14. MALARIA ....................................................................................................... 43
    12.14.1. Malaria (1880) ...................................................................................... 43
    12.14.2. Dr. John Cropper - Malaria Researcher in Palestine ............................ 44
  12.15. MYASTHENIA GRAVIS (1892) .......................................................................... 44
  12.16. PELLAGRA ..................................................................................................... 45
    12.16.1. Reports in the US (1700’s - 1902) ........................................................ 45
    12.16.2. Civil War – 20th Century ....................................................................... 45
    12.16.3. Pellagra (1914- 1926)........................................................................... 45
  12.17. PROTEUS SYNDROME: ELEPHANT MAN DIAGNOSED (1884) .............................. 46
  12.18. PULSE (300 C.E.) ......................................................................................... 46
  12.19. SCURVY (14TH – 20TH CENTURY) ..................................................................... 46
    12.19.1. Background .......................................................................................... 46
    12.19.2. Scurvy - William Stark (1741-1770)...................................................... 47
  12.20. SEPSIS (C.E. 129-1973) ............................................................................... 47
  12.21. SITOPHOBIA (FOOD REFUSAL) AND ANOREXIA NERVOSA IN VICTORIAN ASYLUMS
          (19TH CENTURY) ............................................................................................ 47
  12.22. VERTIGO AND EPILEPSY (ANCIENT TIMES TO PRESENT) .................................... 48

                                                             4
  12.23.       ULCERS (16TH CENTURY TO 1885) .................................................................. 48
13.     DISEASES OF LEADERS .................................................................................. 48
  13.1.        WAS LOUIS XIV INFECTED WITH PARASITES? .................................................. 48
  13.2.        HEMOPHILIA AND QUEEN VICTORIA OF ENGLAND (1837-1901).......................... 49
  13.3.        WHAT DID GEORGE WASHINGTON DIE FROM?................................................. 49
  13.4.        KING GEORGE III AND ACUTE INTERMITTENT PORPHYRIA (1739 – 1820).......... 49
  13.5.        FRANKLIN D. ROOSEVELT (1882 – 1945)........................................................ 50
14.     ENDOCRINOLOGY............................................................................................ 50
  14.1.        BACKGROUND (19TH AND 20TH CENTURIES) ...................................................... 50
  14.2.        CASTRATI (16TH CENTURY – 1924) ................................................................. 50
  14.3.        DIABETES MELLITUS (1ST CENTURY C.E.) ........................................................ 51
  14.4.        SURGERY (PREHISTORIC TIMES TO PRESENT).................................................. 51
15.     GENERAL MEDICINE........................................................................................ 52
  15.1.    DR. PHILIP BARROUGH (1587) - FIRST BOOK ON MEDICINE IN ENGLISH ............. 52
  15.2.    WILLIAM BEAUMONT AND EARLY STUDIES OF GASTRIC SECRETION ................... 52
  15.3.    ANTONIO BENIVIENI (1443-1502)- TRAILBLAZER PATHOLOGIST........................ 52
  15.4.    HENRY INGERSOLL BOWDITCH (1808-1892) AND OLIVER WENDELL HOLMES
           (1809-1894)................................................................................................. 53
  15.5.    FREDERICK CHOPIN (1810 – 1849) – DID HE HAVE CYSTIC FIBROSIS? ............ 53
  15.6.    ABRAHAM LINCOLN AND MEDICAL MALPRACTICE (1858) ................................... 53
  15.7.    JOSEPH LISTER (1827 – 1912) ...................................................................... 54
    15.7.1.    Report 1 ............................................................................................... 54
    15.7.2.    Report 2 ............................................................................................... 54
  15.8.    NOSTRADAMUS - DOCTOR AND PROPHET (1503 - 1566) .................................. 54
  15.9.    JAMES PARKINSON - CHILD ADVOCATE (1755-1824) ....................................... 55
  15.10. LOUIS PASTEUR (1822-1895) ........................................................................ 55
    15.10.1. Pasteur and Koch on American Medicine ............................................ 55
    15.10.2. Work..................................................................................................... 55
  15.11. WILLIAM PROUT - PHYSIOLOGICAL CHEMIST (1785 - 1850) .............................. 56
  15.12. VESALIUS (1514 - 1564)................................................................................ 56
16.     GENERAL TOPICS ............................................................................................ 56
  16.1.    AMPUTATION (NEOLITHIC TIMES - 1810).......................................................... 56
  16.2.    ANATOMY (980 – 1288)................................................................................. 57
  16.3.    ARROW WOUNDS AND THE DEVELOPMENT OF SURGERY ................................... 57
  16.4.    CHOREA ST. VITII (658-739) .......................................................................... 58
  16.5.    DOCTORING AS A PROFESSION ....................................................................... 58
    16.5.1.    Ancient Rome 1.................................................................................... 58
    16.5.2.    Ancient Rome 2.................................................................................... 58
  16.6.    EPHEMERA (15TH –16TH CENTURIES ................................................................ 59
  16.7.    EPIDEMIOLOGY (1830) ................................................................................... 59
  16.8.    ETHICS ......................................................................................................... 59
  16.9.    GERMANS, CELTS AND OTHERS ...................................................................... 60
  16.10. HOSPITALS (820 C.E. TO 1311) ..................................................................... 60


                                                             5
  16.11.       IMAGING (1890-1950).................................................................................... 61
  16.12.       INSANITY PLEA (1857) ................................................................................... 61
  16.13.       MEDICAL EDUCATION (19TH CENTURY) ............................................................ 61
  16.14.       MEDICAL THOUGHT (19TH CENTURY TO PRESENT)............................................ 62
  16.15.       MIDWIFERY (200 C.E.) .................................................................................. 62
  16.16.       NURSING STANDARDS (19TH CENTURY) ........................................................... 63
  16.17.       SOBRIETY AND ALCOHOL CONSUMPTION (1736 – 1871) .................................. 63
17.     GYNECOLOGY .................................................................................................. 63
  17.1.        JAMES MARION SIMS, FATHER OF GYNECOLOGY.............................................. 63
18.     INFECTIOUS DISEASES ................................................................................... 64
  18.1.    ANTHRAX ...................................................................................................... 64
    18.1.1.    Haitian Epidemic (1770) ....................................................................... 64
    18.1.2.    History (Antiquity to 2002) .................................................................... 64
  18.2.    BLACK PLAGUE .............................................................................................. 64
    18.2.1.    General Background (541 – 1970) ....................................................... 64
    18.2.2.    The Black (Bubonic) Plague of 542 ...................................................... 65
    18.2.3.    Bubonic Plague (1348)......................................................................... 65
    18.2.4.    The Great Plague 1665 ........................................................................ 66
    18.2.5.    China (1330s)....................................................................................... 66
  18.3.    CHAGAS DISEASE .......................................................................................... 66
    18.3.1.    Chagas Disease ................................................................................... 67
    18.3.2.    Chagas Disease in Mummies 9,000 Years Ago ................................... 67
    18.3.3.    Chagas Heart Disease ......................................................................... 67
  18.4.    CHOLERA ...................................................................................................... 68
    18.4.1.    Cholera and the Public Health (1854) .................................................. 68
    18.4.2.    Epidemic (1854) ................................................................................... 68
  18.5.    DISEASE TRANSMISSION ................................................................................. 68
    18.5.1.    From Europe to the Americas (16th Century)........................................ 68
  18.6.    ENGLISH SWEATING DISEASE (1485 – 1551) .................................................. 69
  18.7.    FLU .............................................................................................................. 69
    18.7.1.    Spanish Flu of 1918 ............................................................................. 69
    18.7.2.    The 1918-19 Influenza Pandemic in Nigeria ........................................ 70
    18.7.3.    Influenza Pandemic - 1918................................................................... 70
  18.8.    FOURTH DISEASE (17TH CENTURY TO PRESENT) .............................................. 71
  18.9.    HEAD LICE IN THE MIDDLE AGES ..................................................................... 71
  18.10. HEMORRHAGIC FEVER (1545 – 1576) ............................................................ 71
  18.11. LEPROSY ...................................................................................................... 72
    18.11.1. Leprosy in South America (19th Century) ............................................. 72
    18.11.2. Leprosy in NY (2004) ........................................................................... 72
  18.12. MEDIEVAL HOUSEHOLD PEST CONTROL .......................................................... 72
  18.13. SCARLET FEVER EPIDEMICS (1848 –1900) ..................................................... 73
  18.14. LYME DISEASE AND ERYTHEMA MIGRANS (1909 TO PRESENT).......................... 73
  18.15. TICK-BORNE DISEASES (1889 TO PRESENT) ................................................... 73
  18.16. TUBERCULOSIS .............................................................................................. 74
    18.16.1. Gold Therapy For Tuberculosis (1920)................................................. 74


                                                              6
    18.16.2. History .................................................................................................. 74
  18.17. TREATMENT .................................................................................................. 74
  18.18. TYPHO-MALARIA DEBUNKED (19TH CENTURY) .................................................. 75
  18.19. YELLOW FEVER AND POLITICS (1821 -1823 .................................................... 75
19.     MESOPOTAMIA................................................................................................. 75
  19.1.        DENTAL DISEASE IN ANCIENT MESOPOTAMIA (2000 B.C.E.)............................. 75
  19.2.        HEBREW MEDICINE ........................................................................................ 76
20.     MIDDLE AGES ................................................................................................... 76
  20.1.        DARK MIDDLE AGES (400-800 C.E.) .............................................................. 76
  20.2.        HIGH MIDDLE AGES (1200-1400) ................................................................... 77
  20.3.        PADUA: THE RENAISSANCE OF HUMAN ANATOMY AND MEDICINE ....................... 77
  20.4.        THE LATE MIDDLE AGES AND RENAISSANCE (1400-) ....................................... 77
  20.5.        MEDIEVAL MANUSCRIPTS (11TH TO 15TH CENTURIES) ........................................ 78
  20.6.        MEDIEVAL SPAIN (10TH AND 13TH CENTURIES)................................................ 78
21.     MIDDLE-EASTERN MEDICINE ......................................................................... 78
  21.1.        SEREFEDDIN SABUNCUOGLU - TURKISH SURGEON (15TH CENTURY) .................. 79
22.     NEPHROLOGY .................................................................................................. 79
  22.1.        HISTORY OF KIDNEY DISEASE (1ST CENTURY C.E.)........................................... 79
  22.2.        RICHARD BRIGHT (1789-1858)....................................................................... 79
  22.3.        HOMER SMITH FATHER OF NEPHROLOGY (1895 - 1962) .................................. 80
  22.4.        EMERICH ULLMANN - KIDNEY TRANSPLANTATION (1861-1937) ......................... 80
23.     NEUROLOGY..................................................................................................... 80
  23.1.    BABINSKI ....................................................................................................... 80
    23.1.1.    Background .......................................................................................... 80
    23.1.2.    100 Year Anniversary (1896-1996) ...................................................... 81
  23.2.    BRAIN SURGERY (LATE STONE AGE) ............................................................... 81
  23.3.    CAROTID ARTERY COMPRESSION (18TH CENTURY) ........................................... 82
  23.4.    EPILEPSY ...................................................................................................... 82
    23.4.1.    Electrical Theory (1873) ....................................................................... 82
    23.4.2.    Herodotus and Epilepsy ....................................................................... 82
    23.4.3.    Byzantine Emperor Michael IV (11th Century) ...................................... 83
    23.4.4.    Joan of Arc and Epilepsy...................................................................... 83
  23.5.    HEAD INJURY (1830)...................................................................................... 83
  23.6.    THE KNEE JERK (1875).................................................................................. 84
  23.7.    NERVE TRANSMISSION (1822) ........................................................................ 84
  23.8.    NEURONE DOCTRINE (1866) .......................................................................... 84
  23.9.    SEIZURE TREATMENTS (18TH CENTURY) .......................................................... 85
  23.10. LLUIS BARRAQUER-ROVIRALTA (1907) ............................................................ 85
  23.11. JEAN-BAPTISTE BOUILLAUD (1825) ................................................................. 86
  23.12. DR. JULES COTARD (1840-1889) ................................................................... 86
  23.13. SAMUEL COLLINS - COMPARATIVE NEUROLOGY (1618-1710) ........................... 86
  23.14. HARVEY CUSHING - PEDIATRIC NEUROSURGEON (1869 - 1939) ....................... 87


                                                             7
  23.15.      FREUD AND TOURETTE'S SYNDROME (1890 – 1911)........................................ 87
  23.16.      SIR VICTOR HORSLEY (1857 – 1916) - A PIONEER IN NEUROSURGERY ............ 88
  23.17.      WILLIAM WILLIAMS KEEN –NEUROSURGEON (1837-1932) ................................ 88
  23.18.      WILDER PENFIELD - SENSORY MAP................................................................. 88
  23.19.      ROBERT REMAK (1815-1865) – EMBRYOLOGIST/NEUROLOGIST ....................... 89
  23.20.      CHARLES SCOTT SHERRINGTON (1857-1952) - THE SYNAPSE ......................... 89
  23.21.      ROBERT BENTLEY TODD - FATHER OF EPILEPSY (1809-1860).......................... 90
  23.22.      THOMAS WILLIS (1621-1675) - FOUNDER OF MODERN CLINICAL NEUROSCIENCE
              91
24.     ONCOLOGY....................................................................................................... 91
  24.1.       EARLY REPORT OF CANCER IN A CHILD (1564-1617) ....................................... 91
  24.2.       ROSWELL PARK, M.D. (1852-1914) ............................................................... 91
25.     ORTHOPEDICS ................................................................................................. 91
  25.1.       OSTEOGENESIS IMPERFECTA (1844-1849)...................................................... 92
26.     PATHOLOGY ..................................................................................................... 92
  26.1.       FORENSIC ENTOMOLOGY (13TH CENTURY TO PRESENT).................................... 92
  26.2.       "JAKE WALK" - A TOXICOLOGICAL TRAGEDY (1930)......................................... 93
  26.3.       LEAD EXPOSURE (ANCIENT TO MODERN TIMES ................................................ 93
  26.4.       LEAD POISONING KILLED THE CREW OF THE FRANKLIN EXPEDITION? (1845)...... 93
  26.5.       VEGETABLE POISONS AND DEATH (1812) ........................................................ 94
  26.6.       TOBACCO’S HARMFUL EFFECTS IN HISTORY (10444 - 1600S) .......................... 94
  26.7.       RUDOLF VIRCHOW (821 – 1902) .................................................................... 95
  26.8.       RUSSIAN MEDICINE (18TH CENTURY) ............................................................... 95
27.     PSYCHIATRY..................................................................................................... 95
  27.1.       AMNESIA (1892) ............................................................................................ 95
  27.2.       BIPOLAR DISORDERS (100 C.E.) .................................................................... 96
  27.3.       MENTAL ILLNESS (19TH CENTURY)................................................................... 96
  27.4.       RORSCHACH TEST (1884-1922)..................................................................... 96
  27.5.       SCHIZOPHRENIA (1911) ................................................................................. 97
28.     SURGERY.......................................................................................................... 97
  28.1.       BRAIN SURGERY (7,000 B.C.E. – 900 C.E._.................................................. 97
  28.2.       CATARACT SURGERY (5TH CENTURY B.C.E.)................................................... 97
  28.3.       LAPAROSCOPIC SURGERY (1901 TO PRESENT)................................................ 98
29.     VACCINES ......................................................................................................... 99
  29.1.    FIRST GLOBAL VACCINATION OCCURRED IN 1803 ............................................ 99
  29.2.    EMIL VON BEHRING – (1854-1917) – DIPTHERIA AND TETANUS ........................ 99
  29.3.    SMALL POX ................................................................................................... 99
    29.3.1.    Canadian Experience (1798 – 1962).................................................... 99
    29.3.2.    Vaccination in 1830's - Maybe We Should Take Note........................ 100
    29.3.3.    Vaccination - How Long Does It Last? ............................................... 100
30.     WARS............................................................................................................... 100


                                                             8
  30.1.    ILIAD (8TH CENTURY B.C.E.) ......................................................................... 100
    30.1.1.     Battlefield Exacerbated Dysentery ..................................................... 100
    30.1.2.     Wound Management .......................................................................... 101
  30.2.    US CIVIL WAR............................................................................................. 101
    30.2.1.     Lack of Medical Care - Major Cause of Death.................................... 101
    30.2.2.     The Hospital Ship (1862).................................................................... 102
31.     WOMEN IN MEDICINE .................................................................................... 102
  31.1.       AGNODICE – A WOMEN DOCTOR IN ANCIENT GREECE.................................... 102
  31.2.       CLARA BARTON - FLORENCE NIGHTINGALE (1823-1912)................................ 102
  31.3.       MARY ANN BICKERDYKE - WOMAN HEALER IN THE CIVIL WAR (1817-1901) .... 103
  31.4.       DORCAS HAGER PADGET - MEDICAL ILLUSTRATOR (1906-1973) .................... 103
  31.5.       DOROTHY REED - HODGKIN'S DISEASE (1902) .............................................. 103
  31.6.       MARY GRANT SEACOLE - JAMAICAN MEDICINE WOMAN (19TH CENTURY) ......... 104




                                                          9
1.          ALTERNATIVE MEDICINE

     1.1.    Balance of Mind and Body
     It is difficult to appreciate just how unimportant the human brain was considered to
     be for most of the history of science and medicine, before the scientific revolution,
     which started with Isaac Newton (1642-1727). However, even Sir Isaac Newton
     believed in alchemy. Medieval and Renaissance physicians sought to understand
     the mind with a mix of Christian theology and Greek philosophy. The body was
     believed to be divided into three anatomical regions, each designed for its own soul.
     The vegetative soul in the liver was responsible for desires and appetites. The heart
     housed the vital soul, which produced passions and action. The rational soul was
     immaterial and immortal and, hence, could not reside in one specific place in the
     body. But its faculties--such as reason, memory, and imagination--were carried out
     by the body's invisible spirits. These spirits were believed to swirl in three hollow
     chambers in the head known as the ventricles. Anatomy, then, was the study of the
     houses of the souls. But anatomy alone was not enough to account for the life of the
     mind. Physicians also had to understand the fluids that coursed through the body.
     The four humors--black bile, yellow bile, blood, and phlegm--needed to be balanced
     for good health. Humors also gave each individual his or her temperament, be it the
     sad detachment of melancholy or the swift rage of choler. If the humors became
     corrupted or moved to the wrong place in the body, they could cause epilepsy or
     alter the temperament, even lead to madness. Physicians sought to cure many
     psychological disorders by bringing the humors back in balance, typically with
     bleeding and purging or by applying herbs.

     1.2.    Cacao Use in Medicine (16th Century)
     The medicinal use of cacao, or chocolate, both as a primary remedy and as a
     vehicle to deliver other medicines, originated in the New World and diffused to
     Europe in the mid 1500s. These practices originated among the Olmec, Maya and
     Mexica (Aztec). The word cacao is derived from Olmec and the subsequent Mayan
     languages (kakaw); the chocolate-related term cacahuatl is Nahuatl (Aztec
     language), derived from Olmec/Mayan etymology. Early colonial era documents
     included instructions for the medicinal use of cacao. The Badianus Codex (1552)
     noted the use of cacao flowers to treat fatigue, whereas the Florentine Codex (1590)
     offered a prescription of cacao beans, maize and the herb tlacoxochitl (Calliandra
     anomala) to alleviate fever and panting of breath and to treat the faint of heart.
     Subsequent 16th to early 20th century manuscripts produced in Europe and New
     Spain revealed >100 medicinal uses for cacao/chocolate. Three consistent roles can
     be identified: 1) to treat emaciated patients to gain weight; 2) to stimulate nervous
     systems of apathetic, exhausted or feeble patients; and 3) to improve digestion and
     elimination. For the latter, cacao/chocolate countered the effects of stagnant or
     weak stomachs, stimulated kidneys and improved bowel function. Additional treated
     medical complaints have included anemia, poor appetite, mental fatigue, poor
     breast milk production, consumption/tuberculosis, fever, gout, kidney stones,


                                            10
reduced longevity and poor sexual appetite/low virility. Chocolate paste was also a
medium used to administer drugs and to counter the taste of bitter pharmacological
additives. In addition to cacao beans, preparations of cacao bark, oil (cacao butter),
leaves and flowers have been used to treat burns, bowel dysfunction, cuts and skin
irritations.

1.3.   Glass Armonica and Healing (1761)
The Armonica, also called the glass harmonica was invented by Benjamin Franklin
in 1761. In 1757, while in England he attended a concert given on the wine glasses.
He thought it was the sweetest sound he had ever heard but he wanted to hear
more harmonies with his melody. It has been said that if the harp is "the instrument
of the Angels", then the Armonica is "the voice of the Angels". To create the
Armonica, a graduated size bowls with holes and corks in the center were put onto a
horizontal spindle and rotated by a fly wheel and a foot pedal. Moistened fingers
were then rubbed the edges to produce the beautiful sound. Franklin used a most
unique way to identify the notes of the bowls. He painted the seven white keys the
seven colors of the rainbow and the five black keys, white. The instrument
immediately became popular and inspired compositions by Wolfgang Mozart, who
had the opportunity to hear and play one at the house of Franz Anton Mesmer.
Armonica music was used by Mesmer in his séances, because he felt it could
promote healing by propagating a mystical fluid that he called animal magnetism
through the body. After Mesmer's theories were debunked by a highly respected
panel of scientists, the Armonica fell out of vogue. Because Franklin was on the
panel that examined the discredited mesmerism, he indirectly contributed to his own
invention's demise.

1.4.   Leeches (Middle Ages)
Leeches were widely used for healing throughout antiquity and the Middle Ages.
The rabbinic responsa literature acknowledges the use of leeching for the
prevention and treatment of certain illnesses. Classic Jewish sources including the
Bible, Talmud, and Codes of Jewish Law describe leeches and mention their
medicinal use. Although the swallowing of a leech is considered dangerous and may
lead to abdominal swelling, the Talmud describes an oral concoction containing
leeches in wine for patients with enlarged spleens. It is also documented that
engorged leeches placed in salt quickly discharge their blood and can be used
again. Modern plastic and microsurgery have rediscovered the medicinal leech,
Hirudo medicinalis, to reduce venous congestion. The value of this annelid worm
lies in its secretion of an anticoagulant known as hirudin, which has several
advantages over heparin.

1.5.   Licorice (220 B.C. – Present)
The use of the licorice herb goes back centuries in both Western and Eastern
cultures. There is plenty of evidence of licorice's usage over the last 2,000 years in
Europe, including German herbals (1264). Licorice is found in Chinese literature
(220 B.C.E.) and has also been used extensively in India. Traditionally, licorice has
been used for almost everything, with some of the most common uses being for:

                                        11
ulcers, sore throats, insomnia, abdominal pain, bronchitis, blood cleanser, herpes,
abscesses, food poisoning, treatment of cancer, and for the support the adrenal
glands during stress. Licorice is the most heavily used herb in China and is the
number one herbal "drug" in the world.

1.6.   Nightshade (19th Century)
Nightshade plants (Solanaceae) have been utilized as hallucinogenic drugs since
antiquity in nearly every culture. The Solanaceae alkaloids, atropine and
scopolamine, were the active substances in ointment of witches and medieval
anesthetics, and in modern poisons. They are still currently used as hallucinogenic
drugs. In poisonings, a dosage- and substance-dependent clinical picture occurs,
with central and peripheral symptoms. Hallucinations are predominant in the middle
dose range, which explains the drugs' earlier utilization for religious and prophetic
purposes. Respiratory depression and arrest at high doses confirm the use of
scopolamine as a lethal poison. Despite this, the nightshade alkaloids were utilized
in clinical medicine in the 19th century and are still being used in prescription
products.

1.7.   Psychosomatic Medicine (10th – 15th Centuries)
Original elements of psychosomatic medicine were examined by the most important
Byzantine physicians and medical philosophers during the 10th -15th centuries.
These topics addressed the psychosomatic unity of the human personality, plus
much more: psychosomatic disturbances, diseases and interactions, organic
diseases which cause psychical disorders, psychical pathological reactions which
result in somatic diseases, the psychology of the depth of the soul, the
psychosomatic pathogenetic reasons of psychiatric and neurological diseases,
suicide, the influence of witchcraft on psychosomatic affections, and maniac and
demoniac patients. The psychosomatic treatment had a holistic preventive and
curative character and included sanitary and dietary measures, physiotherapy,
curative bathing, strong purgation, pharmaceutical preparations, religious
disposition, psychoanalysis, psychotherapy with dialogue, and the contribution of
the divine. The saint woman physician Hermione (1st - 2nd century) is considered
the founder of psychosomatic medicine.

1.8.   Sozodont Powder Dentifrice and Mrs. Winslow's Soothing Syrup
The Great Patent Medicine Era (1865-1907) was the golden age of nostrums
(unproved, quack, non-prescription medicinal products, sold over-the-counter, and
whose ingredients were usually secret). Making outrageous and unsubstantiated
claims, the makers of dental nostrums purported to effectively treat stained teeth,
bad breath, diseased gums, toothache and teething discomfort. No proof was
required to substantiate the safety and effectiveness of these concoctions.
Advertisements for patent medicines were widespread, appearing in newspapers,
almanacs, magazines, trade cards and multiple other media forms. Many dental
patent medicines contained acids, abrasive substances, alcohol and/or narcotics,
such as heroin, cocaine and morphine. Sozodont Tooth Powder, the most widely
promoted and successful dentifrice of this era, claimed to "harden and invigorate the

                                       12
     gums, purify and perfume the breath and beautify and preserve the teeth from youth
     to old age." Early dental researchers found that this remedy contained harsh
     ingredients (such as acid, sharp abrasives and astringents) which could destroy
     tooth substance. Mrs. Winslow's Soothing Syrup, an extremely popular dental
     nostrum, was intended to quiet a fretful child during the teething process. However,
     it contained generous levels of alcohol and morphine sulfate which could cause
     coma, addiction or death. These two products were eventually removed from the
     market in the 1930s.

2.          ANCIENT EGYPT

     2.1.    Medicinal Plants
     The ancient Egyptians knew many of the therapeutic effects of the medicinal plants.
     This knowledge was taught at home from father to son and formed the first primitive
     pharmacy and medicine schools. Century after century, the ancient Egyptians
     became more and more interested in medical sciences. Temples began to establish
     medical and pharmaceutical schools. Priests of good and honest character with
     scientific background were chosen to become teachers and professors in these
     schools. Another medical and pharmaceutical schools teaching all the scientific
     courses were the Per Ankh or Houses of Life. Special schools were erected inside
     the Royal palaces for the education of the Royal family children, the nobles and the
     court officials comprising all sorts of sciences and arts, specially taught in its own
     Per Ankh, as in Heliopolis and Memphis palaces.

     2.2.    Mummification (Herodotus 450 B.C.E.)
     Chemical treatments were an essential element of ancient Egyptian mummification.
     Although the inorganic salt, natron is recognized as having a central role as a
     desiccant, without the application of organic preservatives the bodies would have
     decomposed in the humid environment of the tombs. The nature of the organic
     treatments remains obscure, because the ancient Egyptians left no written record of
     the process. Secondary textual evidence for mummification is provided by
     Herodotus, Diodorus Siculus, Strabo and Pliny. The most important account is that
     of Herodotus (about 450 B.C.E.), although archaeological evidence shows that by
     this time the process had declined significantly and the best results had been
     achieved centuries before. Herodotus’ account mentions myrrh, cassia, palm wine,
     “cedar oil” (still widely disputed) and “gum. However, he is vague with respect to the
     specific natural products used.

     2.3.    Medicine (2600 B.C.E.)
     Egyptian medicine was marked by a mystical approach to healing, as well as a more
     empirical or rational approach that was based on experience and observation.
     Common diseases of the eyes and skin were usually treated rationally by the
     physician because of their accessible location; internal disorders continued to be
     treated by the spells and incantations of the priest-magician. The earliest physician
     was Imhotep (circa 2600 B.C.E.), renowned for his studies of pathology and
     physiology as well as his expertise as a pyramid builder and an astrologer. The


                                             13
Egyptian physician normally spent years of arduous training at temple schools in the
arts of interrogation, inspection, and palpation (examining the body by touch).
Prescriptions contained some drugs that have continued in use through the
centuries. Favorite laxatives were figs, dates, and castor oil. Tannic acid, derived
principally from the acacia nut, was valued in the treatment of burns. According to
reports of the Greek historian Herodotus, the ancient Egyptians recognized dentistry
as an important surgical specialty.

2.4.   Poliomyelitis (Polio) in Ancient Egypt
Poliomyelitis (Polio) is a viral infection of the anterior horn cells of the spinal chord.
The presence of poliomyelitis can only be detected in those who survive its acute
stage. The shortening of the left leg, which was interpreted as poliomyelitis, was
observed in the an early Egyptian mummy from Deshasheh. The club foot of the
Pharaoh Siptah as well as deformities in the 12th Dynasty mummy of Khnumu-
Nekht are probably the most attributable cases of poliomyelitis. An 18th or 19th
Dynasty funerary staele shows the doorkeeper Roma, with a grossly wasted and
shortened leg accompanied by an equinus deformity of the foot. The exact nature of
this deformity, however, is debated in the medical community. Some favor the view
that this is a case of poliomyelitis contracted in childhood before the completion of
skeletal growth. The equinus deformity, then, would be a compensation allowing
Roma to walk on the shortened leg. Alternatively, the deformity could be the result
of a specific variety of club foot with a secondary wasting and shortening of the leg.

2.5.   Schistosomiasis (bilharziasis) in Ancient Egypt
Of the three main species of the platyhelminth worm Schistosoma, the most
important for Egypt are S. mansoni and S. haematobium. There is a complex life
cycle alternating between two hosts, humans and the fresh water snail of the genus
Bulinus. The infection is caught by humans who come into contact with the free
swimming worm which the snail releases in the water. The worm penetrates the
intact skin and enters the veins of the human host. The main symptom of the
presence of the parasite is hematuria which results in serious anemia, loss of
appetite, urinary infection, and loss of resistance to other diseases. There may also
be interference with liver functions. One of the finest archaeological examples for
the existence of schistosomiasis in ancient Egypt was the discovery of calcified ova
in the unembalmed 21st Dynasty mummy of Nakht. Upon medical examination, the
mummy not only exhibited a preserved tapeworm, but also ova of the Schistosoma
haematobium and displayed changes in the liver resulting from a schistosomal
infection.

2.6.      Tuberculosis
Sir Marc Armand Ruffer, Professor of Bacteriology at Cairo Medical School in the
early 1900's, reported the presence of tuberculosis (Pott's disease) of the spine in
Nesparehan, a priest of Amun of the 21st Dynasty. The spine shows the typical
features of Pott's disease with collapse of thoracic vertebra, producing the angular
kyphosis (hump-back). A well known complication of Pott's disease is the
tuberculous suppuration moving downward under the psoas major muscle, towards

                                          14
     the right iliac fossa, forming a very large psoas abscess. Ruffer's report has
     remained the best authenticated case of spinal tuberculosis from ancient Egypt. All
     known possible cases, ranging from the Predynastic to 21st Dynasty are
     predynastic specimens collected at Naqada by Petrie and Quibell in 1895, as well
     as nine Nubian Specimens from the Royal College of Surgeons of England. There is
     very little doubt that tuberculosis was the cause of pathology in most, but not all,
     cases. In some cases, it was not possible to exclude compression fractures,
     osteomyelitis, or bone cysts as causes of death.

3.          ANCIENT GREECE

     3.1.    Medicine
     Ancient medicine integrated three components: experience (empirical observation),
     religion/magic and speculations of natural philosophers. In contrast, Greek medicine
     began to investigate the true causes of health and diseases, thus laying foundations
     for diagnosis, prognosis and treatment. Hippocrates made a synthesis of existing
     philosophical opinions from the point of view of a physician. His 58 writings were
     preserved in the collection "Corpus Hippocraticum". The most relevant writing in it,
     "Peri fyseos anthropu" (On the nature of man), is ascribed to Hippocrates' son-in-
     law Polybos who developed the ancient humoral-pathological theory. In explaining
     the human organism and its processes, Polybos integrated ancient teachings on
     four basic humors (humoral theory), elements and qualities with observations of
     manifestations of health and disease. Normal condition (health) was defined as
     balance between the body fluids (eukrasia) and external environment. If this balance
     was disturbed, the result was dyskrasia, i.e. disease studied by pathology.
     According to Hippocrates, disease causes could be understood only through
     empirical study, and that while man has the power to overcome disease, the right
     diet is necessary to keep harmony in body fluids of an organism. The role of a
     physician was just to support the nature. "Prognosis", another writing included in
     "Corpus Hippocraticum", reflected Hippocrates' understanding of prognosis as a
     necessary development of diagnosis based on past knowledge (anamnesis) and
     present observation.

     3.2.    Remedies
     A large number of remedies, known as "pharmaca" in Greek, which are currently
     used in medical practice have been traced back to the Hellenic period.
     Archeological data, as well as literary and scientific texts, suggest that the ancient
     Greek physicians knew how to use many remedies from herbs, plants, metals and
     minerals, and animals. These remedies were given orally in liquid form (katapotia in
     Greek), in poultice form, or in the form of ointments and eye-drops (collyria). The
     main problem of ancient pharmacology was that chemistry had not yet become a
     science so that it was difficult to distinguish the individual effects of each of the
     substances. However, especially during the classical period (6th-4th century B.C.E.)
     and from the end of the Hellenic period and thereafter, remedies were presented
     clearly and in detail in prescriptions, giving medicine a more scientific profile of their
     workings.


                                              15
3.3.   Aristotle (384 - 322 B.C.E.)
Aristotle was born in 384 B.C.E. He was the son of a physician at Stageira in
Macedonia, and was one of the most noted philosophers and scientists of the
ancient world. Once a student of Plato at his Academy in Athens, Aristotle adopted
his own methods of inquiry different from that of his teacher. Unlike Plato, Aristotle
felt that one could, and in fact must, trust one's senses in the investigation of
knowledge and reality. Aristotle's writings cover a wide variety of subjects, from
human and animal anatomy, to metaphysics, statesmanship, and poetry. His
treatises on human anatomy are lost, but his many works on animals advocate
direct observation and anatomical comparisons between species through dissection.
He wrote extensively on the soul, classifying the souls of different forms of life and
inanimate objects, including the earth and the heavens. Aristotle wrote extensively
on animal life and reproduction, making him in many ways the founder of Western
natural philosophy. Aristotle died in 322 B.C.E.

3.4.   Cult of Asclepius (6th Century B.C.E.)
Beginning in the sixth century B.C.E., health resorts, or sanctuaries, known as
Asklepia (because they were presided over by the god of healing Asclepius) sprang
up all over the Mediterranean. The cult of Asclepius was at the same time a religion
and a system of therapeutics. His sanctuaries, such as those at Tricca, Epidauros,
Cos and Pergamon, were built outside the towns on particularly healthy sites. In
these Asklepia special rites were observed. After purificatory preparation, baths,
fasting and sacrifices, the patient would spend the night in the god's precinct or
temple, a process known as "sleeping in" (enkoimesis, incubatio). The fashion of
incubation seems not to have really caught on until the fourth century when the
great healing centers as Cos and Epidauros were established. Thus, we have
rational and thaumaturgic medicine, i.e. dream therapy, developing together through
the Hellenistic period pari passu, i.e. in equal steps, rather in the manner of
astronomy and astrology. During the night as the patient slept, Asclepius would
appear to the patient in a dream and give him advice. In the morning the priests
would interpret the dream and explain the god's precepts. Patients would thank
Asclepius by tossing gold into the sacred fountain and by hanging ex-votos on the
walls of the temple. Hippocratic principles were directly opposed to magic and ritual.
However, the continuing success throughout antiquity of the cult of Asclepius
showed very clearly that medicine was never fully divorced from its religious.

3.5.   Chiron - The Inventor of Medicine
In Greek mythology, the centaur, Chiron, was wounded by Hercules. Though he
was immortal, it is said that he invented medicine in order to heal himself. He taught
Asclepius the art of healing, which became the source of all divine medical
knowledge among the Greeks. Chiron was also the teacher of the hero, Achilles,
who was thought to have had some special medical knowledge.




                                        16
3.6.   Dioscorides of Anazarbus- Father of Pharmacology (40-90 C.E.)
Dioscorides of Anazarbus was a Greek physician born in southeast Asia Minor in
the Roman Empire in the first few decades of Common Era (CUE.). During his
lifetime, Dioscorides traveled extensively seeking medicinal substances from all
over the Roman and Greek world. He benefited greatly from the ease of travel
across wide stretches of territory under the control of the Roman Empire at the
height of its growth. Between about 50-70 C.E., he wrote his fundamental work,
known in Latin as De materia medica. This five book study focused upon "the
preparation, properties, and testing of drugs" and became the most central
pharmacological work in Europe and the Middle East for the next sixteen centuries.
As was the case with many Greek medical texts, De materia medica was treated as
dogma for many years. By the mid-16th century, however, his message that
investigation and experimentation were crucial to pharmacology began to emerge
and modern research into medicines began.

3.7.   Erasistratus of Chiros (304 - 250 B.C.E.)
Erasistratus of Chiros (ca. 304-ca. 250 B.C.E.) was a Greek anatomist who
continued the systematic investigation of anatomy begun by Herophilus in
Alexandria. Erasistratus described the cerebrum and cerebellum, studied nerves
(which he believed to be hollow) and the valves of the heart. He distinguished
between veins and arteries, believing the latter to be full of air. He proposed
mechanical explanations for many bodily processes, such as digestion. Erasistratus
believed in a tripartite system of humors consisting of nervous spirit (carried by
nerves), animal spirit (carried by the arteries), and blood (carried by the veins).

3.8.   Galen (131 – 201 C.E.)

   3.8.1. Report 1
Galen was a Greek physician who was born in Pergamum in Asia Minor. Galen
began to study medicine at the age of 16, and at 20 went to Alexandria. He became
a surgeon to the gladiators at Pergamum at the age of 30, and after four years he
went to Rome in 162 as the physician to the court of the Emperor Marcus Aurelius.
After returning to Pergamum for three years, he went back to Rome in 169 C.E. and
stayed there for the last 30 years of his life. Besides dealing with clinical problems
and treatment, Galen studied anatomy, physiology, and pharmacology. He is
especially known for his anatomical studies and his scientific methods. He studied
the work of Erasistratus (c. 290 B.C.E.) and Herophilus (300 B.C.E.), and dissected
both the Barbary ape and pigs. Galen established that the arteries contain blood
and not air, as had been taught by Aristotle. He did not, however, understand the
circulation of the blood, but thought that it flowed to and fro like the tides, with the
arterial surges being quite separate from those in the veins. His teaching was
accepted as authoritative by the Church. He did not recognize the healing force
which Hippocrates (c. 410 B.C.E.) had attributed to nature. However, he insisted
that the varying symptoms of diseases should be studied and individually treated,
with the treatment depending upon the organs affected by the disease. Galen wrote



                                         17
more than 400 books, of which about 100 are now known. His work remained
virtually unchallenged until the more critical Renascence period.

   3.8.2. Report 2
Galen was born in Pergamos in Asia Minor in the year 131 C.E. (common era). After
receiving medical training in Smyrna and Alexandria, he gained fame as a surgeon
to the gladiators of Pergamos. He was eventually summoned to Rome to be the
physician of the Emperor Marcus Aurelius. Galen spent the rest of his life at the
Court writing an enormous corpus of medical works until his death in 201 C.E.
Taking Hippocrates notions of the humors and pathology, Galen incorporated the
anatomical knowledge of noted Alexandrians such as Herophilus of Chalcedon
(335-280 B.C.E.). A supporter of observation and reasoning, he was one of the first
experimental physiologists, researching the function of the kidneys and the spinal
cord in controlled experiments. Galens works in many ways came to symbolize
Greek medicine to the medical scholars of Europe and the Middle East for the next
fifteen centuries. While his message of observation and experimentation were
largely lost, his theories became dogma throughout the West. In the mid-16th
century, his message that observation and investigation were required, allowed for
modern methods of research to finally come into place.

   3.8.3. Report 3
Galen hailed from Pergamon, an ancient Roman center of civilization which
contained a library second in importance only to Alexandria. Galen's training was
eclectic and although his chief work was in biology and medicine, he was also
known as a philosopher and philologist. Training in philosophy was, in Galen's view,
not merely a pleasant addition to, but an essential part of the training of a doctor.
His treatise entitled "That the Best Doctor is also a Philosopher" provides a rather
surprising ethical reason for a doctor to study philosophy. The profit motive, says
Galen, is incompatible with a serious devotion to the art. Galen felt that a doctor
must learn to despise money and he often accused his colleagues of avarice.
Galen's first professional appointment was as surgeon to the gladiators in
Pergamon. In his tenure as surgeon, he gained much experience and practical
knowledge in anatomy from the combat wounds he was compelled to treat. After
four years he immigrated to Rome where he attained a brilliant reputation as a
practitioner and a public demonstrator of anatomy. Among his patients were the
emperors Marcus Aurelius, Lucius Verus, Commodus and Septimius Severus.

3.9.   Hippocrates (5th Century B.C.E.)

   3.9.1. Topic 1
Hippocrates of Cos was a Greek physician who lived around the 5th and 4th
centuries B.C. Although he believed that "humors" and "foul vapors" caused
disease, many of his teachings are consistent with modern medicine. Hippocrates
believed that nature healed all wounds and the physician was a modifier of that
natural healing. He taught that medications could produce a countereffect to the
symptoms of a disease, "opposite through opposite". Although public opinion during


                                       18
     his time condemned dissections of the human body, Hippocrates did perform them
     to a limited extent. He also emphasized the observation of external signs and
     symptoms in establishing diagnoses. In addition, Hippocrates dealt well with
     fractures and was a master in the use of splints. He even treated fractures of the
     skull with trepanning (removing a circular area of bone) and urged his students to be
     careful not to mistake suture lines for fractures. Most of all, Hippocrates was a good
     observer. This can best be demonstrated by his "Aphorisms" or his advice to
     physicians.

        3.9.2. Topic 2
     It was in the 5th century B.C.E. that Hippocrates name and image began to emerge
     as a leader in medical research and thought. Hippocrates is generally credited with
     turning away from divine notions of medicine and using observation of the body as a
     basis for medical knowledge. Prayers and sacrifices to the gods did not hold a
     central place in his theories, but changes in diet, beneficial drugs, and keeping the
     body "in balance" were the key. Central to his physiology and ideas on illness was
     the humoral theory of health, whereby the four bodily fluids, or humors, of blood,
     phlegm, yellow bile, and black bile needed to be kept in balance. Illness was caused
     when these fluids became out of balance, sometimes requiring the reduction in the
     body of a humor through bloodletting or purging. The Hippocratic Corpus, or the
     collected writings attributed to Hippocrates, contains about sixty works on a variety
     of medical topics, including diagnosis, epidemics, obstetrics, pediatrics, nutrition,
     and surgery.

     3.10. Plato and Diet (5th-4th century B.C.E.)
     Plato (5th-4th century B.C.E.), one of the most important philosophers of Greek
     antiquity, left a valuable spiritual heritage, compiled in his famous dialogues. His
     teachings extended to almost every single field of human knowledge. Among other
     philosophical concepts, Plato's works are imbued with the fundamental principle of
     moderation. This spirit is characteristically evident in his references to human diet.
     According to Plato, a moderate and thus a healthy diet, consists of cereals,
     legumes, fruits, milk, honey and fish, and that meat, confectionery and wine should
     be consumed only in moderate quantities. Plato added that excesses in food lead to
     ailments and should be avoided. Plato considered physicians responsible for the
     regulation of human diet, since medicine was considered a science and not merely
     an art as in the case of cookery. The dietary pattern presented in Platonic dialogues
     shares many common components with the highly-reputed Mediterranean diet. As a
     whole, Plato's writings represent a valuable source for the study of the nutritional
     customs during the classical period of ancient Greece.

4.          ANCIENT ROME

     4.1.    Caesarean Section
     The Caesarean section operation did not derive its name from the fact that Julius
     Caesar was supposedly born in this manner. It was called Caesarean because the
     Roman, or Caesarean, law demanded that when a pregnant woman died, her body


                                             19
could not be buried until the child had been removed. The law also stipulated that a
Caesarean section could not be performed on a living pregnant woman until the
tenth month of gestation. Ancient physicians were unable to save the life of the
mother in such cases, thus the procedure was rarely performed. We know from
ancient sources that Julius Caesar could not have been born by Caesarean section,
because his mother, Aurelia, lived to be an adviser to her grown son.

4.2.   Ophthalmology in Ancient Rome
Physicians in classical times devoted great attention to eye diseases, from both a
surgical and clinical point of view. Instruments consistent in size and shape with use
in ophthalmology are frequently mentioned in the inventory of Roman and Etruscan
surgical implements found in archaeological excavations. Moreover, ancient Roman
writings, imply that such knowledge and practices were much older, and that eye
physicians were numerous, specially in the northern regions of the Empire. These
physicians were really specialized in the treatment of eye diseases and were
capable of performing at least 24 different kinds of treatment. Purulent ciliary
infections were treated by applying specially designed warm or hot instruments.
Pterygium (wedge-shaped growth on the bulbar conjunctiva) was surgically
removed with a procedure based on the use of a special instrument, a thin "hook"
with a curved point, which was well described by the Roman physician Aulus
Cornelius Celsus in the first century A.D. Cataracts were treated with a specialized
procedure, that included the lowering of the opaque crystalline using a special
"needle" with cutting edges. In the Northern provinces of the Empire, treatment of
conjunctivitis led to the development of a wide variety of treatment, including
cauterization of the superficial veins of the temporal region. Medical therapies
included the application of ointments which, were manufactured in the form of solid
rods or "pastels", produced after the condensation of mixtures of complex
composition. These were obtained by the pulverization of several simple
substances, which were mixed in a liquid, often consisting of wine or vinegar. The
mixtures were blended with a sort of resin and made into rods with square section,
which were subsequently dried. While still wet, the rods were imprinted with a mark,
indicating the designation of the ointment and the name of the preparer. A classic
preparation was the so-called "ointment of Philones", composed of opium, tutsia and
ceruxa, substances with strong detergent and analgesic properties.

4.3.   A Gladiator's Blood as a Cure For Epilepsy
Between the first and the sixth century a single theologian and several medical
authors reported that the consumption of a gladiator's blood or liver could cure
epilepsy. The origins of the sacred or apoplectic properties of blood of a slain
gladiator, likely lie in Etruscan funeral rites. Although the influence of this religious
background faded during the Roman Republic, the magical use of gladiators' blood
continued for centuries. After the prohibition of gladiatorial combat in about 400
C.E., an executed individual (particularly had he been beheaded) and his blood,
became the "legitimate" successor to that of the gladiator. Occasional indications in
early modern textbooks on medicine as well as reports in the popular literature of
the 19th and early 20th century document the existence of this ancient magical


                                         20
     practice, even into modern times. Spontaneous recovery of some forms of epilepsy
     may be responsible for the illusion of therapeutic effectiveness and for the
     confirming statements by physicians who have commented on this cure.

5.          ANCIENT WORLD

     5.1.    Birth Control in the Ancient World
     Women in the ancient world practiced birth control with little interference from
     religious or political authorities. A precise knowledge of plants which could either
     block conception or cause abortion was resident in the oral culture of herbalists and
     midwives. One of the most common contraceptive agents used in the ancient
     Mediterranean world was silphium, which grew exclusively in the country of Cyrene
     in North Africa. Since Cyrene was the sole exporter of the plant, it became the city’s
     official symbol on its coinage and it remained the city’s primary source of income
     until the first century B.C.E.. Other plants used in classical times as contraceptives
     or abortafacients included pennyroyal, artemisia, myrrh, and rue. In Aristophanes’s
     comedy Peace, first performed in 421 B.C.E., Hermes provides Trigaius with a
     female companion. Trigaius wonders if the woman might become pregnant. “Not if
     you add a dose of pennyroyal,” advises Hermes. Pennyroyal grows in the wild and
     would have been readily available to ancient women. Recent studies show that
     pennyroyal contains a substance called pulegone that terminates pregnancy in
     humans and animals.

     5.2.    Diseases
     The unique conditions of preservation of the Copper age mummy found in the Val
     Senales glacier (Italy) has allowed the analysis of the general state of health of a
     man of the late European prehistory. Investigations conducted within the
     organizational framework of an International Research Project revealed the
     presence of a series of alterations, that, in a broad sense, can be considered of
     paleopathological interest. These can be classified as: 1) post mortem lesions such
     as scalp erosions, alopecias (balding), soft tissue loss in the right gluteal region,
     joint dislocations; 2) lesions that occurred during life such tattooings, dental wear,
     trichorrexis nodosa (bamboo hair), nail hypoplasia, moderate osteoarthritis of the
     lumbar vertebral column and of the hip joints, and ankle osteosclerosis. The
     palaeopathological analysis of this unique mummy has shed vivid light on the
     mutual interactions between disease, environment, and culture, that shaped human
     life in a distant past.

     5.3.    Gases
     Ancient historical references consistently describe an intoxicating gas, produced by
     a cavern in the ground, as the source of the power at the oracle of Delphi. These
     ancient writings are supported by a series of associated geological findings.
     Chemical analysis of the spring waters and travertine deposits at Delphi show the
     presence of methane, ethane, and ethylene. The effects of inhaling ethylene, a
     major anesthetic gas in the mid-20th century, are similar to those described in the
     ancient writings. It is believed that the probable cause of the trancelike state of the


                                              21
Priestess (the Pythia) at the oracle of Delphi, during her mantic sessions, was a
result of inhaling ethylene gas or a mixture of ethylene and ethane from a naturally
occurring geological vent.

5.4.   History
In ancient Egypt by the 3rd Dynasty, the physician emerged as an early form of
scientist. The Egyptians practiced embalming but their anatomical knowledge
remained at a low level and they attempted only minor surgical procedures. In
Assyria and Babylonia, the liver was considered the seat of the soul and was
studied to determine the intentions of the gods. Hebrew medicine was influenced by
the Old Testament and emphasized hygienic regulations, midwifery, feminine
hygiene, separation of the sick, and disinfection of materials capable of harboring
and transmitting germs. Ancient Hindu medicine became quite sophisticated,
especially in the field of operative surgery. Ancient Chinese medicine utilized
acupuncture and a wide array of drugs, including opium.

5.5.   Deformity In The “Boxing Boys”
A late Bronze Age wall painting, known as the Boxing Boys (c. 17th-16th century
B.C.E.), was excavated in the ancient town of Akrotiri on the Greek island of Thera.
The artist depicted a combination of structural anatomical adjustments which are
diagnostic of spondylolisthesis (spondylolisthes is a forward slippage of one of the
lumbar vertebrae). The accurate portrayal of the surface appearance of this
condition, suggests that the artist painted directly from a live subject. Thus, the
Boxing Boys mural may be the earliest visual record of a sports-induced injury.
Although the meaning of the wall paintings is unclear, the wild goats (agrimia) on the
adjoining walls simulate swayback as a reflection of the boy's torso deformity. The
abnormal morphology appears to be the earliest achievement of transforming
disease into aesthetic charm on a monumental scale.

5.6.   Genes and Archeology - A Different Kind Of History
The spread of agriculture that started in the Near East about 10,000 years ago
caused a dramatic change in the European archaeological record. It is still unclear if
that change was caused mostly by movement of people or by cultural
transformations. In particular, there is disagreement on what proportion of the
current European gene pool is derived either from the pre-agricultural, paleolithic
and mesolithic people, or from neolithic farmers immigrating from the south-east. To
begin to characterize the mtDNA gene pool of prehistoric Europe five human
remains were examined from the Eastern Italian Alps, dated between 14,000 and
3,000 years ago. Three of them yielded sufficient amount of mtDNA for analysis.
DNA extracts were prepared in two laboratories, and PCR products from the first
hypervariable segment of the mtDNA control region were cloned and sequenced.
Together with the 5,200 year old 'ice man', these DNA sequences showed that
European mtDNA diversity was already high at the beginning of the neolithic period.
All the neolithic sequences have been observed in contemporary Europeans,
suggesting genealogical continuity between the neolithic and present-day European
mtDNA gene pool. The mtDNA sequence from a 14,000 year-old specimen was not

                                        22
     observed in any contemporary Europeans, raising the possibility of a lack of
     continuity between the mesolithic and present-day European gene pools.

     5.7.    Practitioners of Medicine (2100 B.C.E.)
     By examining the surviving medical tablets it is clear that there were two distinct
     types of professional medical practitioners in ancient Mesopotamia. The first type of
     practitioner was the ashipu, often called a "sorcerer." One of the most important
     roles of the ashipu was to diagnose the ailment. In the case of internal diseases, this
     most often meant that the ashipu determined which god or demon was causing the
     illness. The ashipu also attempted to determine if the disease was the result of
     some error or sin on the part of the patient. The phrase, "the Hand of..." was used to
     indicate the divine entity responsible for the ailment in question, who could then be
     propitiated by the patient. The ashipu could also attempt to cure the patient by
     means of charms and spells to entice away or drive out the spirit causing the
     disease. The ashipu could also refer the patient to a different type of healer called
     an asu. An asu was a specialist in herbal remedies, and in older treatments of
     Mesopotamian medicine was frequently called "physician" because he dealt in what
     were often classifiable as empirical applications of medication. For example, when
     treating wounds the asu generally relied on three fundamental techniques: washing,
     bandaging, and making plasters. All three of these techniques of the asu appear in
     the world's oldest known medical document (c. 2100 B.C.E.).

6.          ARTS AND DISEASE

     6.1.    Dante and Melancholy (1265 –1321)
     The history of melancholy depression is rich with images of movement retardation
     and mental dysfunction. The recent restoration of psychomotor symptoms to the
     diagnostic terminology of affective disorder is not novel to the students of medieval
     melancholia. The move back to the biology of this psychomotor dysfunction with the
     technical advances in brain imaging in recent years only echoes centuries-old
     writings on the centrality of movement changes in the depressive condition. The
     Inferno, the first cantica of Dante Alighieri's Commedia, has a wonderful abundance
     of allusions to the importance of psychomotor symptoms in describing the
     depressed individual. Slowed steps, garbled speech, frozen tears, these and many
     other images keep the physical manifestations of psychomotor suffering in the
     forefront of the reader's mind. Considering Medieval and Renaissance writings on
     melancholy suffering, it is fitting that Dante shows a bodily illness reflected in the
     hellish torments visited on the damned. From the souls of the sullen to those of the
     violent, the panorama of psychomotor symptoms plays a prominent role in the poem
     as well as in the medical and literary prose of succeeding centuries.

     6.2.    I Got Rhythm: George Gershwin and Birth Control in the 1930s
     Gershwin's song 'I Got Rhythm' serves as a backdrop representing the social
     context of the inter-war years. On center stage is a particular aspect of the history of
     birth control - the application of a new theory of ovulation to contraception. Starting
     in 1928, a series of experiments revealed a biochemical rhythm in the female


                                              23
reproductive cycle, which contradicted the widespread idea that ovulation and
pregnancy could occur at any time. This discovery was applied to a new
contraceptive method, the rhythm method, which enjoyed significant popularity
during the 1930s, especially among Catholics. For a short period, women could join
Ethel Merman in the refrain 'I got rhythm, I got my man, who could ask for anything
more.' Unfortunately, the rhythm method has not lived up to its promise.

6.3.   Pearl Buck and PKU (1921 – 1960)
In 1921, Pearl S. Buck gave birth to a daughter, Carol, who became severely
retarded, and was eventually institutionalized at the Vineland Training School in
New Jersey. To help pay for her daughter's care, Buck wrote The Good Earth in
1931, and then other novels and biographies about her life in China, for which she
was awarded the Nobel and Pulitzer Prizes, and honored around the world. Years
later, she published The Child Who Never Grew, a short piece about her daughter's
retardation that also revealed her desperate search for answers and good clinical
care. Dr. Asbjorn Folling distinguished phenylketonuria (PKU) from other forms of
childhood retardation in the mid-1930s, and new assays and biochemical findings
eventually led to ways to circumvent the devastating effects of PKU. But for Carol
Buck, these advances came too late. It was not until the 1960s that physicians
confirmed that her severe retardation was caused by PKU.

6.4.   Vincent van Gogh (1853-1890)
Vincent van Gogh (1853-1890), who committed suicide at the age of 37, had an
eccentric personality, unstable moods, and suffered from recurrent psychotic
episodes during the last 2 years of his extraordinary life. Despite limited evidence,
well over 150 physicians have ventured a perplexing variety of diagnoses of his
illness. Henri Gastaut, in a study of the artist's life and medical history published in
1956, identified van Gogh's major illness during the last 2 years of his life as
temporal lobe epilepsy, precipitated by the use of absinthe in the presence of an
early limbic lesion. In essence, Gastaut confirmed the diagnosis originally made by
the French physicians who had treated van Gogh. However, van Gogh had earlier
suffered two distinct episodes of reactive depression, and there are clearly bipolar
aspects to his history. Both episodes of depression were followed by sustained
periods of increasingly high energy and enthusiasm, first as an evangelist and then
as an artist.

6.5.   Robert Louis Stevenson (1850 –1894) - Hereditary Hemorrhagic
       Telangiectasia
Chronic illness played a major role in the life and literary success of Robert Louis
Stevenson. However, the exact nature of his chronic illness remains unclear. It is
possible that Stevenson had hereditary hemorrhagic telangiectasia, genetic disease
which affects blood vessels. This would explain his chronic respiratory complaints,
recurrent episodes of pulmonary hemorrhage, and his death, at age 44 years, of
probable cerebral hemorrhage. It would also explain his mother's hitherto
unreported but apparent stroke, at age 38 years.



                                         24
     6.6.    Sleep Apnea - Lewis Carroll and William Shakespeare
     Both Lewis Carroll and William Shakespeare appear to have made clinical
     observations of sleep apnea syndromes. Long before these syndromes were
     discovered by medical science, these great authors seem to have understood
     something about their physiological mechanisms. The somnolent dormouse in Alice
     in Wonderland indicates that his problem is one of sleep and breathing and would
     be subject to modern treatment for obstructive apnea. Shakespeare, in Henry IV,
     presents a case of obstructive apnea along with a case of Cheyne-Stokes breathing
     and uses the plot of these history plays to explain by analogy the theoretical basis
     for periodic breathing.

7.          BASIC SCIENCE

     7.1.    Golgi and Neuropsychiatry (19th Century)
     Camillo Golgi was born in July 1843 in Corteno, a village in the mountains near
     Brescia in northern Italy. Golgi studied medicine at the University of Pavia from 1865
     to 1868, where he attended as an intern at the Institute of Psychiatry directed by
     Cesare Lombroso (1835-1909). Golgi also worked in the laboratory of experimental
     pathology directed by Giulio Bizzozero, a brilliant young professor of histology and
     pathology. Bizzozero discovered the homeopathic properties of bone marrow and
     introduced Golgi to experimental research and histological techniques. One of the
     most unrecognized aspects of Golgi's life was his deep interest in neuropsychiatry.
     Golgi attended the Clinica per le Malattie Nervose e Mentali in Pavia directed by
     Cesare Lombroso, the founder of modern criminology. Golgi was involved in
     research on the etiology of psychiatric ailments and during this short period of time
     he produced significant theoretic advances in clinical psychiatry. However, very
     soon he started to criticize the conceptual approach as well as the nosological
     system proposed by his academic mentor. In July 1868 Golgi left Lombroso's school
     in search for a more rational method of studying brain functions and diseases. In
     spite of his anatomical approach to the central nervous system, he always
     maintained curiosity in the phenomenology of functional and organic mental
     disorders. This predisposition is supported by his capability to relate clinical
     observations to neuropathological findings.

     7.2.    Robert Hooke (1635 – 1703)
     Relatively little is known about Robert Hooke's life. He was born on July 18, 1635, at
     Freshwater, on the Isle of Wight, the son of a churchman. He was apparently largely
     educated at home by his father, although he also served an apprenticeship to an
     artist. Hooke devised the compound microscope and illumination system, one of the
     best such microscopes of his time. This microscope was used in his demonstrations
     at the Royal Society's meetings. With it he observed organisms as diverse as
     insects, sponges, bryozoans, foraminifera, and bird feathers. Hooke's reputation in
     the history of biology largely rests on his book Micrographia, published in 1665.
     Micrographia was an accurate and detailed record of his observations and was a
     best-seller of its day. Hooke died in London on March 3, 1703.



                                             25
     7.3.    Anton van Leeuwenhoek (1632-1723)
     Anton van Leeuwenhoek (1632-1723) was an unlikely scientist. A tradesman of
     Delft, Holland, he came from a family of tradesmen, had no fortune, received no
     higher education or university degrees, and knew no languages other than his
     native Dutch. This would have been enough to exclude him from the scientific
     community of his time completely. Yet with skill, diligence, endless curiosity, and an
     open mind free of the scientific dogma of his day, Leeuwenhoek succeeded in
     making some of the most important discoveries in the history of biology. It was he
     who discovered bacteria, free-living and parasitic microscopic protists, sperm cells,
     blood cells, microscopic nematodes and rotifers, and much more. His researches,
     which were widely circulated, opened up an entire world of microscopic life to the
     awareness of scientists. At some time before 1668, Anton van Leeuwenhoek
     learned to grind lenses, made simple microscopes, and began observing with them.
     He seems to have been inspired to take up microscopy by having seen a copy of
     Robert Hooke's (1635-1703) illustrated book Micrographia, which depicted Hooke's
     own observations with the microscope and was very popular. Leeuwenhoek is
     known to have made over 500 "microscopes," of which fewer than ten have survived
     to the present day.

8.          CARDIOLOGY

     8.1.    Diuretic Properties of Mercury (19th Century)
     It was not until 1919 that the diuretic properties of mercury were observed in
     patients with syphilis. In the same year, the beneficial effects of mercurial diuretics
     were shown in a patient with severe rheumatic heart disease and anasarca (edema,
     swelling). However, mercury had been used much earlier for the treatment of dropsy
     without clear guidelines. William Stokes (1804-1878) was a pioneer of the treatment
     of heart failure, focusing on the beneficial diuretic properties of mercury. Stokes
     made several important clinical observations in his well known treatise “The
     Diseases of the Heart and the Aorta.” First, he provides precise guidelines on when
     and how to use mercury. Second, he realizes the importance of mercury for the
     treatment of decompensated heart failure. He expands on the cyclical nature of
     frequent decompensation in congestive heart failure, the relationship of clinical
     deterioration and reduced urine output, and the importance of reestablishing urinary
     flow to ameliorate dyspnea. Third, he attempts to define the mechanism of action of
     mercury "... if any of the characteristic action of mercury can be perceived unless we
     include diuresis." Finally, he gives interesting guidelines on the dosage and side
     effects of mercury. These observations on the treatment of "congestive" heart failure
     became an important contribution to the understanding of heart failure
     pathophysiology and the design of treatment regimens.

     8.2.    Tetralogy of Fallot (1673)
     Tetralogy of Fallot is a type of heart problem which consists of four different heart
     defects. The first defect is called a ventricular septal defect (VSD). This is a hole
     between the two bottom chambers (ventricles) of the heart. The second defect is
     called Pulmonary Stenosis. This is a narrowing at or just below the pulmonary valve.

                                             26
The third part of Tetralogy of Fallot involves the aorta being positioned over the
ventricular septal defect instead of in the left ventricle. Finally, the right ventricle in
infants born with Tetralogy of Fallot is more muscular than normal. The chronicle of
tetralogy of Fallot is part of a dramatic evolution in cardiology, cardiac surgery, and
understanding of the developing heart. Many new tools and concepts have evolved
since Steno of Denmark first described the defect in 1673, and since Fallot of
Marseilles coined the term tetralogy in 1888. Four major eras of progress can be
recognized. The 1st, the era of pathologic anatomy, culminated in the publication of
Maude Abbott's Atlas of Congenital Cardiac Disease in 1936. The next, the era of
clinicophysiology and surgery, was highlighted by the 1st Blalock-Taussig
anastomosis in 1944, by open-heart surgery 10 years later, and by a new team
approach to cardiology. The 3rd, or infant era, began in the mid 1970s with
successful intracardiac repair in infants, the rise of echocardiography, and the
introduction of prostaglandin therapy. The current era of cardiac development
(beginning in the 1990s) gives hope for early understanding of the molecular basis
of tetralogy. Tribute is due to the surgical and medical pioneers, and to the pioneer
patients and their families, for revolutionary changes in diagnosis and treatment.
The challenge of the next 100 years lies in increased understanding of the
molecular biology of the defect and in preserving the blend of humanism,
scholarship, and skill that have graced the advances of the past 3 centuries.

8.3.   William Harvey (1578 – 1657) - Cardiac Output and the Hour Glass
In 1636, the Rostock (Germany) professor of medicine and the art of poetry, Peter
Lauremberg (1585-1639), was one of the earliest to cite the concept of blood
circulation, which had been discovered by William Harvey. In 1628 William Harvey
proved the existence of blood circulation by calculating the "cardiac output in a half
an hour (semihora)". The answer to the question why Harvey chose half an hour as
the time range can be found in the way of measuring time at that period. The
sandglasses were turned half-hourly in maritime navigation and the wheel-clocks on
shore had only the hour-hand. Improved chronometry was one of the prerequisites
for measuring cardiac output. The minute-hand became usual after 1700 and the
second-hand shortly thereafter. Taking into consideration the alterations of cardiac
output, being able to measure seconds was one of the most important discoveries
for cardiac diagnosis, prognosis and therapeutics.

8.4.   William Senhouse Kirkes (1822-1864) - Pathogenesis of Hypertension
The realization of the key role for raised intra-arterial pressure as a pathogenetic
agent in hypertension is usually credited to Ludwig Traube. However, Traube in his
writings gives credit for the idea to a little-known English doctor, William Senhouse
Kirkes (1822-1864). Kirkes' main interest was in cardiology and vascular disease,
and in 1852, gave the first account of embolism in infective endocarditis. Three
years later, he published a study of apoplexy in Bright's disease, in which he pointed
clearly to the role of raised intra-arterial tension in the causation of arterial disease,
a point that had eluded Bright, Johnson, and other contemporaries. Kirkes died at
the age of 42 while working on a book summarizing his work on cardiology and



                                          27
renal disease, and the neglect of his contribution probably resulted from his early
death.

8.5.   Rudolph Matas (1860-1957)– Vascular Surgeon
Temporary occlusion of large vessels (the Matas test) is a test of the adequacy of
collateral circulation and is part of daily clinical practice. Nevertheless, only a few
clinicians are aware of Rudolph Matas (1860-1957) and his pioneering work in
medicine. During his lifetime, Rudolph Matas witnessed enormous progress in
medicine and greatly contributed to its evolution. He is unanimously recognized as
the father of modem vascular surgery for his creation and popularization of
aneurysmorrhaphy, a technique for the definitive treatment of aortic and peripheral
aneurysms. He also made significant contributions to the then burgeoning fields of
anesthesia, critical care, and infectious disease (yellow fever in particular). In 1911,
Matas wrote a landmark article in which he described a challenge test to assess the
degree and efficacy of the collateral circulation in patients under consideration for
permanent occlusion of a major vessel. Matas studied the feasibility of such a test
by temporarily occluding the carotid and femoral arteries in dogs for variable periods
of time. In the introduction to his seminal article on the subject, he stated that "the
chief object of this inquiry has been to determine whether the large arteries can be
occluded long enough to make it possible to observe the effect of the arrested
circulation in the territory supplied by the occluded vessel, without irreparably
damaging the artery during the period of observation." Matas definitively achieved
his stated goal. The Matas test, although greatly modified by contemporary
endovascular techniques to be safer and more reliable, is in essence still routinely
performed worldwide 90 years after its initial description.

8.6.   Woldemar Mobitz (1924) - 2nd Degree Atrioventricular Block
In 1924, Woldemar Mobitz, an early 20th century German internist, analyzed
arrhythmias by graphing the relationship of changing atrial rates and premature
beats to AV conduction. Through an astute mathematical approach, he was able to
classify second-degree atrioventricular block into 2 types, subsequently referred to
as Mobitz type I (Wenckebach) and Mobitz type II (Hay). Type I AV block was most
often due to digitalis and was reversible. There were no associated pathological
findings. Type II AV block frequently progressed to complete AV block and was
associated with seizures, death, and pathological findings.

8.7.   Jean-Baptiste de Senac (1693-1770) – Arterial Pulse
For two centuries after William Harvey, the arterial pulse was often regarded as
independent of the heartbeat. This misunderstanding was mainly because of the
frequent failure of the irregular heart to elicit a radial pulse: the "pulse deficit" of later
times. Harvey observed ineffective palpitation of the atrium just before death. This
was probably atrial fibrillation. He established the origin of the heart beat in the right
atrium. Harvey's observations were confirmed and extended by Jean-Baptiste de
Senac in the mid-eighteenth century. De Senac correlated gross irregularities
(palpitation) with necropsy observation of mitral valve disease and dilatation of the
left ventricle. He emphasized the origin of the heart's irregularity from the distended

                                           28
     atrium consequent on distension or reflux of blood irritating the atrial wall. De Senac
     also commented on disconcerted action and rippling of the ventricular wall before
     final cessation of movement in a dying heart (ventricular fibrillation). De Senac's
     ideas were a century and a half ahead of his time.

     8.8.    William Withering and the Discovery of Digitalis (1775)
     Digitalis is an example of a cardio-active or cardiotonic drug, and has been used in
     the treatment of heart conditions ever since its discovery in 1775. The discovery of
     digitalis is accredited to the Scottish doctor William Withering. While working as a
     physician in Staffordshire in the 18th Century, Withering’s girlfriend got him
     interested in plants and botany - so much so, that in 1776 he published a huge
     treatise. In 1775, one of his patients came to him with a very bad heart condition
     and since Withering had no effective treatment for him, thought he was going to die.
     The patient, being an independent type, went instead to a local gypsy, took a secret
     herbal remedy, and promptly got much better! When Withering heard about this, he
     became quite excited and searched for the gypsy. After much bargaining, the gypsy
     finally told her secret that the herbal remedy was made from a whole concoction of
     things, but the active ingredient was the purple foxglove, digitalis purpurea. The
     potency of digitalis extract had been known since the dark ages, when it had been
     used as a poison for the mediaeval 'trial by ordeal', and also used as an external
     application to promote the healing of wounds. In fiction, the homicidal use of digitalis
     has appeared in the writings of Mary Webb, Dorothy Sayers and Agatha Christie.
     The fraudulent use of digitalis in the support of claims for disability because of heart
     disease has occurred, and one large conspiracy of physicians and lawyers occurred
     in a swindle of insurance companies during the 1930s. Although there were two
     pharmaceutical manufacturing blunders that occurred in Belgium and Holland that
     resulted in numerous deaths, the medical profession seemed rather slow to
     recognize the nature of these small epidemics of poisoning. Instances of psychiatric
     illness with digitalis seem well documented. The story of digitalis toxicity continues
     into the present, and physicians should be vigilant regarding the drug's potential for
     poisoning that can result from ignorance of proper dosage, pharmacodynamics or
     drug interactions.

9.          DENTISTRY

     9.1.    Etruscan Dentistry (700 B.C.E.)
     Whereas the Greeks theorized on dental problems, the Etruscans were more
     practical and had skilled dentists. As early as 700 B.C.E., they were able to make
     dental appliances with exceptional skill. Partial dentures, of the bridgework type,
     were found in Etruscan tombs. Wide bands of pure gold were soldered together to fit
     over the natural teeth. A substitute tooth went into one of the bands to keep it in
     place. Specimens have been preserved in museums throughout Italy. This type of
     bridgework was not to be done again until the l9th century, as the Dark Ages saw a
     degradation of the civilization built up in Europe by the Roman Empire. In the
     Twelve Tables of the Roman Law, it was allowed that anyone "whose teeth shall



                                              29
have been fastened together (juncti) with gold" could be so buried. It was illegal in
all other cases to bury gold with a corpse.

9.2.   Jaw Fractures (1863)
In 1863, James Baxter Bean, a Southern physician and dentist, invented the
interdental splint. This device was used to treat hundreds of Confederate soldiers
who had received gun shot-related facial and jaw injuries during the Civil War. Made
of vulcanized India-rubber, the splint provided a dramatic breakthrough in the
treatment of maxillofacial wounds. In an Atlanta hospital, Dr. Bean utilized his
invention by establishing the first ward devoted exclusively to the treatment of jaw
fractures. He also invented an apparatus that manufactured and administered
nitrous oxide. Additionally, Bean's groundwork in casting aluminum as a denture
base material led to Taggart's later invention (in 1907) of the casting machine.

9.3.   Necrotizing Ulcerative Stomatitis (Noma) (16th – 17th Centuries)
Noma (necrotizing ulcerative stomatitis, stomatitis gangrenosa, or cancrum oris) is a
devastating orofacial gangrene that occurs mainly among children. The disease has
a global yearly incidence of 140,000 cases and a mortality rate of approximately
90%. Patients who survive noma generally suffer from its sequelae, including
serious facial disfigurement, trismus, oral incontinence, and speech problems. The
medical history of noma indicates that the disease was already known in classical
and medieval civilizations in Europe. In the 16th and 17th centuries, Dutch surgeons
clearly described noma as a clinical entity and realized that the popular name "water
canker" was not sufficient, since this quickly spreading ulceration in the faces of
children was different from "cancer." In the eighteenth century, awareness that
noma was related to poverty, malnutrition, and preceding diseases such as measles
increased in northwestern Europe. In the first half of the nineteenth century,
extensive surgical procedures were described for the treatment of the sequelae of
noma. At the end of that century, noma gradually disappeared in the Western world
because of economic progress, which gave the poorest in society the opportunity to
feed their children sufficiently. Only in the twentieth century were effective drugs
(sulfonamides and penicillin) against noma developed, as well as adequate surgical
treatment for the sequelae of noma. These modes of treatment remain inaccessible
for the many present-day victims of noma because of their extreme poverty. The
only truly effective approach to the problem of noma throughout the world is
prevention, namely, combating the extreme poverty with measures that lead to
economic progress.

9.4.   Oral Disease (25,000 years ago)
Oral disease has been a problem for humans from the beginning of history. Skulls of
Cro-Magnon peoples, who inhabited the earth 25,000 years ago, show evidence of
tooth decay. The earliest recorded reference to oral disease is from an ancient
(5000 B.C.E.) Sumerian text that describes toothworm as a cause of dental decay.
There is historical evidence that the Chinese used acupuncture around 2700 B.C.E.
to treat pain associated with tooth decay.



                                        30
9.5.   Periodontal Disease

   9.5.1. Bartolomeo Eustachio (1520-1574)
Bartolomeo Eustachio (1520-1574), a major anatomist and physician of the Italian
Renaissance, made very significant contributions toward our knowledge of the
anatomy and physiology of the dentition. His work included the first descriptions of
the structure of the dental pulp and of the periodontal membrane. His treatise on the
teeth, "Libellus de Dentibus", published in 1563, provides remarkable descriptions of
the dental pulp, the periodontal membrane, the development of both sets of teeth
from dental follicles, the trigeminal nerve, and other oral structures. Eustachio also
had very modern ideas concerning the treatment of periodontitis, including the
curettage of granulation tissue to promote reattachment of the gingival tissue.

   9.5.2. History
Periodontal (gum) diseases are considered as old as the history of mankind.
Magical, religious and herbal treatments were demonstrated in almost all early
writings. However, methodical, carefully reasoned therapeutic approaches did not
exist until the middle-ages, and modern treatment with a scientific base and
sophisticated instrumentation did not develop until the 18th century. Prior to the
1950s, periodontal diseases were mostly treated by root debridement and the
extraction of the affected teeth. Until the 1970s, it was primarily the symptoms of
periodontal diseases that were treated. The goal was radical elimination of the
periodontal pocket (resective therapy). The means were gingivectomy, flap
procedures and osseous surgery. The disadvantages were the massive sacrifice of
periodontal tissues, lack of regeneration and clinically elongated teeth. These
disadvantages, along with the realization of the importance of causative agents,
raised questions about the necessity of total pocket elimination, and the control of
subgingival infection by a thorough scaling and root planing (nonsurgical therapy).
Scaling and root planing, with and without antibiotics, became the most commonly
used treatment during the 1980s. Comparative longitudinal studies, surgical versus
nonsurgical, demonstrated that both surgical and nonsurgical therapy result in
limited regeneration and healing with a long junctional epithelium.

9.6.   Tooth Care (5000 B.C.E. – 1000 C.E.)
During the years 3000 - 5000 B.C.E., Egyptians made toothpaste using a recipe of
powdered ashes of hooves of oxen, myrrh, powdered and burned egg shells and
pumice. Directions were given that all should be mixed together, but there were no
specific instructions as to how the powder should be used. It has been assumed that
the ancient Egyptians used their fingers to rub the mixture onto teeth. The
toothstick, the forerunner of the toothbrush had not, as far as is known, been
discovered at that time. The development of toothpaste began as long ago as 300 -
500 B.C.E. in China and India. According to Chinese history, Huang-Ti studied the
care of teeth and claimed different types of pain felt in the mouth could be cured by
sticking gold and silver needles into different parts of the jaw and gum. The Greeks
and Romans developed a leaden instrument for the extraction of teeth and were
also the first to bind loose teeth together and to support artificial teeth by means of

                                        31
      gold wire. With the fall of the Roman Empire, the evolution and development of
      toothpaste became less clear and little is known of any changes until 1000 C.E.
      During these times, evidence shows the Persians further developed toothpaste.
      According to writings, advice was given on the dangers of using hard toothpowders
      and recommendations were made to make toothpowder from burnt hartshorn, the
      burnt shells of snails and oysters and burned gypsum. Other Persian recipes
      included dried animal parts, herbs, honey and minerals. One formula for
      strengthening teeth included green lead, verdigris, incense, honey and powdered
      flintstone.

      9.7.    Toothworm
      The concept of a toothworm, which according to popular belief, caused caries and
      periodontitis, has existed in diverse cultures and across the ages. During the
      Enlightenment, however, the theory of the toothworm was assigned by medical
      doctors almost exclusively to superstition. Even so, the idea that toothache was
      caused by gnawing worms held on even into this century. There were many different
      ideas with regard to the appearance of toothworms. In England, for instance, it was
      thought that the toothworm looked like an eel. In Northern Germany, people
      supposed the toothworm to be red, blue, and gray and in many cases the worm was
      compared to a maggot. The gnawing worm was held responsible for many evils and,
      in particular, was blamed for toothache provoked by caries. In popular medicine,
      numerous therapies were applied in order to eradicate the toothworm. In addition to
      the fumigations with henbane seeds, which allowed the toothworm to develop in the
      form of burst seeds, there were also magical formulas and oaths.

10.          DERMATOLOGY

      10.1. Joseph Plenck (1735-1807)
      Dr Joseph Plenck, the Viennese protodermatologist was professor and secretary of
      the Imperial Medical Josephine Academy. Plenck introduced the systematization of
      dermatovenereological diseases based on their paradigmatic differences, which is
      deemed as "the only (system) with pretensions to accuracy". A man of diversified
      interests and a fruitful author, he wrote many treatises covering various fields from
      dermatology, venereology, and dentistry to surgery, obstetrics, anatomy, pediatrics,
      pharmacology, and botany. This remarkable physician definitely left a deep trace in
      the history of dermatology and venereology, and marked the transition from text-
      based to visually dependent culture in the field of dermatovenereology.

11.          DISCOVERIES

      11.1. The First Isolated Antibiotic
      One of the earliest areas of scientific exploration in the field of antibiotics was
      whether harmless bacteria could treat diseases caused by pathogenic strains of
      bacteria. By the late 19th century there were a few notable breakthroughs. In 1877,
      Louis Pasteur showed that the bacterial disease anthrax, which can cause
      respiratory failure, could be rendered harmless in animals with the injection of soil


                                             32
bacteria. In 1887, Rudolf Emmerich showed that the intestinal infection cholera was
prevented in animals that had been previously infected with the streptococcus
bacterium and then injected with the cholera bacillus. While these experiments
showed that bacteria could treat disease, it was not until a year later, in 1888, that
the German scientist E. de Freudenreich isolated an actual product from a
bacterium that had antibacterial properties. Freudenreich found that the blue
pigment released in culture by the bacterium Bacillus pyocyaneus arrested the
growth of other bacteria in the cell culture. Experimental results showed that
pyocyanase, the product isolated from B. pyocyaneus, could kill a multitude of
disease-causing bacteria. While pyocyanase while the first antibiotc discovered, it
unfortunately proved toxic and unstable, and could not be developed into an
effective drug.

11.2. Aspirin (Ancient Assyria to 1892)
The Assyrians and the Egyptians were aware of the analgesic effects of myrtle and
willow leaves for joint pains. Hippocrates recommended chewing willow leaves for
analgesia in childbirth and the Reverend Edward Stones is acknowledged as the
first person to scientifically define the beneficial antipyretic effects of willow bark. At
the beginning of the 19th century salicin was extracted from willow bark and purified.
Although the French chemist Charles Gerhardt was the first to synthesize aspirin in
a crude form, the compound was ignored. Aspirin was later rediscovered by Felix
Hoffmann, who reportedly tested the agent on himself and on his father, who
suffered from chronic arthritis. Sir John Vane elucidated aspirin's active mechanism
as an inhibitor of prostaglandin synthetase and received the Nobel Price in Medicine
for this work in 1982. Two isoform of cyclooxygenase (COX-1 and COX-2) have now
been identified, each possessing similar activities, but differing in characteristic
tissue expression. As a result of the marketing of aspirin, Bayer Laboratories rose to
the heights of the pharmacological world. Pfizer and Merck now both market COX-2
inhibitors.

11.3. Celsius Thermometer Scale (1742)
In 1742 the Swedish astronomer Anders Celsius published a paper in the Annals of
the Royal Swedish Academy of Science, entitled "Observations on two persistent
degrees on a thermometer". This paper is the origin of the Celsius temperature
scale. After providing a background on the various ways of expressing temperature
used at that time, Celsius presented an account of his experiments with two "fixed
points" for a temperature scale: 1) the temperature of thawing snow or ice and 2) the
temperature of boiling water. The idea to use the freezing point of water as a
temperature calibration point was not new and had already been suggested by
Reamur and Newton as well as by the less well-known contemporary scientists
Martins, Weitbrecht and Poleni. Celsius, however, used the melting point rather than
the freezing point, i.e. thawing snow or ice rather than freezing water. "This
experiment", Celsius writes, referring to placing a thermometer in thawing snow, "I
have repeated many times during two years in all winter months and all kind of
weather, and during different barometric changes, and always found precisely the
same point on the thermometer.


                                          33
11.4. Chemistry and Medicine (19th Century)
Chemical research by certain physicians in Britain in the early 19th century occurred
in the context of medical traditions founded on vitalism, distillation analysis, and
limited chemical knowledge. Urine chemistry figured prominently in this period
together with the analysis of kidney and bladder stones. Richard Bright's team
studying albuminuria was the first clinical research school in Britain. William Prout's
survey of physiological chemistry, based on meticulous attention to analysis, was
the best summary of human metabolism before Justus Liebig's Animal Chemistry.
Liebig's ideas influenced all physicians who were interested in chemistry. Henry
Bence Jones based his medical practice on Liebig's theories. His research relating
urinary phosphates to diet and exercise revealed the so-called Bence Jones
proteins and investigated the distribution and persistence of drugs in the body.
J.L.W. Thudichum used analytical skills learned from Liebig in his brain chemistry
work. George Owen Rees investigated the composition of urine and the relationship
between urine and blood, using Liebig's practical methods. These and similar
studies showed that chemistry could improve clinical medicine, and that chemistry
could also reveal the onset of disease even before clinical symptoms developed,
thus offering valuable support to preventive medicine. Interestingly, so many
physicians resisted the introduction of chemistry that progress toward the
establishment of clinical chemistry in nineteenth-century Britain was slow.

11.5. Cytopathology (20th Century)
By the end of the 19th century, exfoliated cancer cells had been described in all of
the types of specimens in which they are found today. However, it was not until Drs.
Papanicolaou and Traut published their account of the diagnosis of uterine cancer
from exfoliated cells (1941 and 1943) that cytopathology acquired the momentum to
develop into the powerful presence that it has in human medicine today. These and
the subsequent publications by Papanicolaou stimulated the development and
application of cytopathology worldwide, resulting in abundant literature on the
subject and a galaxy of outstanding practitioners. The 1980s saw the development
and widespread use of aspiration cytology followed in the 1990s by the development
of automated screening systems, marking the latest stage in the evolution of
cytopathology.

11.6. Debridement (18th Century to Present)
Debridement is a well established modality for management of traumatic and non-
traumatic wounds. The word debridement originates from the word "debris" in
French and English and means the removal (excision) of the debris. Debridement
was used for the first time during the 18th century in the surgical context and meant
"wound incision." For French surgeons, it has retained to this day its original
meaning. In medical English, though, the use of the term has been marred by
persisting confusion about its definition. Two quite different surgical procedures still
compete for the definition of debridement: wound incision and wound excision.
Incision is used to release pressure (such as in escharotomy) or to drain a collected
fluid (such as in abscess drainage). These procedures are also at the center of a


                                         34
modern controversy about the management of gunshot wounds. The "tug of war"
between excision and incision, dramatic as it sounds, is not based on the clinical
reality. These are two different procedures with two different indications. The
orthodox doctrine, inherited from military surgeons, consists of aggressive tissue
excision around the bullet track. This radical policy is being challenged by advocates
of a more conservative approach. Minimal tissue excision is sufficient and safe in
many cases, provided careful monitoring of the wound is instituted. Wound incision
alone to relieve tension and allow drainage is possible in certain cases. Surgical
debridement may be very extensive such as in fasciatus, or moderate such as in
burns or minimal such as abrasion and open fractures.

11.7. Fever (17th and 18th Centuries)
The medical concept of fever has undergone profound changes throughout the
centuries. Galen of Pergamon considered fever as a systemic disease in itself, and
it was only between 17th and 18th century that Hermann Boerhaave provided a
more careful evaluation of the clinical phenomena related to fever. Apart from
incorrect theories, a major obstacle to the development of a rational study of fever
has been the lack of appropriate instruments of measurement. In effect, the clinical
thermometer was not diffusely used in everyday medical practice until the mid 19th
century. During this same period Ignaz Semmelweiss postulated that the
pathological-anatomical changes recorded in women who had died because of
puerperal fever, represented a pathological reality, presenting with a whole cohort of
symptoms and signs, among them fever. Even if enormous progress has been
made in the 20th century with regard to fever, which is currently considered a
clinical sign of many different diseases, its etiologic assessment remains a
challenge. In fact, in 1961 the clinical picture of 'Fever of Unknown Origin' was
officially defined. Since such diagnostic labeling is in effect a cover for our inability to
discover the real causes of fever, just as it was retained to be many centuries ago.

11.8. Handwashing As Preventative Medicine (19th Century)
Ignaz Philipp Semmelweis, born in 1818 in Buda, Hungary. Semmelweis received
his MD in 1844 in Vienna, where he was appointed to be an assistant at the
Maternity Hospital. Very soon, Semmelweis became distressed at the number of
patients who died from puerperal infection, commonly known as childbed fever.
After several months of investigation, Semmelweis noticed that the death rate in
Ward One, where doctors and medical students were in charge, was around 29%,
while the death rate in Ward Two, where midwives were in charge, was only 3%.
The final clue came when a colleague of Semmelweis's, Doctor Jakob Kolletschka,
received a cut during the autopsy of a woman who had died of childbed fever. The
cut became infected, and Doctor Kolletschka died in 1847 of puerperal infection. To
Semmelweis, the solution became obvious. In May 1847, he ordered all doctors,
students and midwives in the hospital to wash their hands thoroughly in chlorinated
water before every examination or delivery. When Semmelweis ordered the student
doctors to wash their hands, many of them became outraged. Nevertheless, under
his new rule, the death rate from childbed fever dropped to below 1%. Year after
year Semmelweis provided clear proof that handwashing saved lives, and year after


                                          35
year he was ridiculed and criticized in scientific journals, and by leading
obstetricians in Europe. In 1861, Semmelweis published his principal work, The
Cause, Concept and Prophylaxis of Childbed Fever, in which he carefully explained
how handwashing by doctors would save thousands of lives every year. After years
of attempting to persuade other physicians to follow his ideas Semmelweis was
admitted to a mental hospital in Vienna in August of 1865, after suffering a mental
breakdown, and died shortly thereafter. Today, Semmelweis is hailed as a hero, the
"Savior of mothers". But we must never forget how long and hard he had to fight for
his ideas, because they were not part of the "accepted" science of his day.

11.9. Opioids

   11.9.1.   History of Opium
In 3400 B.C.E., the opium poppy, opium thebaicum, was cultivated in lower
Mesopotamia. The Sumerians called it Hul Gil, the “joy plant.” The Sumerians’
knowledge of poppy cultivation passed to the Assyrians, the Babylonians, and
ultimately, the Egyptians. By 1300 B.C.E.., the Egyptians were cultivating opium or
thebaicum, named for their capital city of Thebes. From Thebes, the Egyptians
traded opium all over the Middle East and Europe. Throughout this period, opium’s
effects were considered magical or mystical. By 500 B.C.E., the Greek physician,
Hippocrates, dismissed the idea that opium was "magical." Instead, he noted its
effectiveness as a painkiller and a styptic (a drug used to staunch bleeding.)
Around 330 B.C.E., Alexander the Great introduced opium to the people of Persia
and India, where the poppies later came to be grown in vast quantities. By 400 C.E.,
opium was first introduced to China by Arab traders.

   11.9.2.   Heroin and Other Opium Alkaloids (1898)
September 19, 1998, marked the centenary of the introduction of heroin by Friedrich
Bayer & Co. Interestingly, heroin was developed by the same research team which
introduced aspirin. The development of heroin was driven by its ability to act as a
cough suppressant to assist breathing in patients with severe lung disease. The
German term HEROS refers to an ancient Greek hero who was honored as a
demigod on account of his deeds. Augustus Matthiessen, who had studied with
Bunsen at Heidelberg, focused his research on the opium alkaloids. Later, he was
joined by Charles Alder Wright in a collaboration that led to the discovery of the
emetic apomorphine. After Matthiessen's death in 1874, Wright synthesized several
morphine esters including acetylcodeine, acetylmorphine, and diacetylmorphine. It
was not until 1898 that further reference was made to the pharmacological activity of
diacetylmorphine. Joseph von Mering, a physician who was to become famous for
his discovery of the hypnotic barbiturates, included the drug among 18 morphine
derivatives that he tested for E Merck of Darmstadt. von Mering was particularly
impressed with ethylmorphine, a compound synthesized by Grimaux in 1881,which
he found to be efficacious in the alleviation of coughs, even in patients with
pulmonary tuberculosis in whom codeine had proven ineffective. In January 1898,
Merck marketed ethylmorphine as a cough suppressant, under the proprietary name
of dionin. Initial expectations of this drug were high and it was hailed as superior to


                                        36
codeine. Ethylmorphine was the first semi-synthetic morphine derivative to be
introduced into the clinic and probably influenced the subsequent decision of F
Bayer & Co to introduce heroin for similar clinical purposes.

11.10.    Lipids (1824)
By 1824, Chevreul had demonstrated that fats were esters of glycerol and fatty
acids of differing chain length. However, at the time, it was thought that fats could be
synthesized only by the plant kingdom. By 1850, it had been found from balance
studies that animals also could synthesize fats from carbohydrates. The caloric
value of fat was determined in the 1860s and shown to be more than double that of
carbohydrate. In 1907, it was shown that this was also true when fat was used as a
source of energy for physical work. The special value of cod liver oil for the
prevention and treatment of rickets was well known by 1850 but was not to be
explained until much later.

11.11.    Nitroglycerin and Nitric Oxide (19th Century)
Ascanio Sobrero discovered nitroglycerine (NG) in 1847. Sobrero first noted the
violent headache produced by minute quantities of NG on the tongue. In 1849,
Constantin Hering tested NG in normal volunteers, and observed that headache
was caused with "such precision ". Hering pursued NG ("glonoine") as a
homeopathic remedy for headache, believing that its use fell within the doctrine of
"like cures like". In 1851, Alfred Nobel recognized the potential of NG and began its
manufacturing in Sweden, while overcoming the hazardous handling problems.
During the mid-19th century, scientists in Britain took an interest in the newly
discovered amyl nitrite, which was recognized as a powerful vasodilator. In 1867,
Lauder Brunton, the father of modern pharmacology, used amyl nitrate to relieve
angina, noting the pharmacological resistance to repeated doses. In the early 20th
century, many worked on in vitro actions of nitrate-containing compounds, although
little progress was made towards understanding the cellular mode of action. In 1977,
Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on
vascular smooth muscle. Robert Furchgott and John Zawadski recognized the
importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and
Louis Ignarro and Salvador Moncada, in 1987, identified endothelial-derived relaxing
factor (EDRF) as NO.

11.12.    Penicillin (1928)
In August 1928, Alexander Fleming returned from a vacation to his usually messy,
disordered laboratory. In one of the Petri dishes that had not been touched by the
Lysol, he noticed an unusual phenomenon: separate colonies of staphylococci and,
near the dish's edge, a colony of mold approximately 20 mm in diameter. The
finding proved to be a watershed in the history of medicine. This discovery lay
dormant for some time before other researchers took up the challenge to investigate
its clinical possibilities. Two investigators at Oxford, Sir Howard Walter Florey and
Ernst Boris Chain, brought penicillin's potential for medical use to fruition and, along
with Fleming, shared the 1945 Nobel Prize for Medicine. The discovery and



                                         37
      development of penicillin represent one of the most important developments in the
      annals of medical history.

      11.13.    Shoe Fitting Fluoroscope (1920 –1950)
      One of the most conspicuous nonmedical uses of the x-ray was the shoe-fitting
      fluoroscope. It allowed visualization of the bones and soft tissues of the foot inside a
      shoe, purportedly increasing the accuracy of shoe fitting and thereby enhancing
      sales. From the mid 1920s to the 1950s, shoe-fitting fluoroscopes were a prominent
      feature of shoe stores in North America and Europe. Despite the widespread
      distribution and popularity of these machines, few have studied their history. The
      public response to shoe-fitting fluoroscopes changed from initial enthusiasm and
      trust to suspicion and fear, in conjunction with shifting cultural attitudes to radiation
      technologies.

      11.14.    X-Rays (1895)
      When x-rays were discovered by Roentgen in 1895, he was quick to realize the
      importance of this mysterious new kind of ray. As early as 1896, x-rays were already
      being used in surgery and medicine, replacing Bell's telephonic needle probe. The
      telephonic needle probe could only detect metallic objects by sound and was,
      therefore, limited to the location of objects such as bullets. As x-ray diagnoses
      became more accurate, radiological techniques were gradually improved over the
      years and progressed from examination of the skeleton to imaging complex internal
      organs. The x-ray became vital in the detection of tuberculosis, for which it is still
      used today. Through the use of opaque substances such as barium sulfate it
      became possible to visualize the digestive tract and later advances in photographic
      techniques made visible the brain and almost all parts of the body. Meanwhile the
      dangers of radiation were recognized, and after 1930, safety measures were
      introduced to protect radiologists and patients against overexposure. In the hundred
      years since the discovery of x-rays, the ever-widening scope of radiology has made
      it a fundamental resource in medical diagnosis and treatment.

12.        DISEASES

      12.1. Diabetes (1674)
      In 1674, Thomas Willis reported that the presence of urine 'as sweet as honey' was
      the pathognomonic sign of diabetes mellitus. In the 19th Century, several reactions
      for the detection of glucose in urine were proposed and glucose measurement
      became common in European laboratories. A case of diabetes mellitus, diagnosed
      by Namias, the head of the Women's Section of the Medicine Department of Venice
      Hospital, was reported in 1863. The patient was a 34-year-old woman admitted to
      the hospital for polydypsia, polyuria, bulimia and fatigue. Urine was weighed for 2
      months and the relative density ranged from 1.045 to 1.038. Glucose was measured
      in the urine using Moore, Trommer and Fehling reagents. A few days after
      admission, laboratory tests showed a urine glucose concentration of 7.69% and a
      blood glucose level of 547 mg% (upper limit of normal is around 120). The assays
      were carried out in the Clinical Laboratory of Venice Hospital, founded in 1863,


                                               38
directed by Giovanni Bizio, one of the first chemists who graduated at Padua
University. By 1863, chemical analyses were commonly carried out in Venice as in
the other parts of Habsburg empire.

12.2. Dwarfism Ancient Egypt (5th Dynasty)
Of the 207 known representations of dwarfism, the majority are achondroplastic, a
form resulting in a head and trunk of normal size with shortened limbs. The statue of
Seneb is perhaps the most classic example of dwarfism in ancient Egypt. A tomb
statue of the dwarf Seneb and his family, all of normal size, goes a long way to
indicate that dwarfs were accepted members in Egyptian society. Other examples
include the 5th Dynasty statuette of Chnoum-hotep from Saqqara, a Predynastic
drawing of the "dwarf Zer" from Abydos, and a 5th Dynasty drawing of a dwarf from
the tomb of Deshasheh. Skeletal evidence, while not supporting the social status of
dwarfs in Egyptian society, does corroborate the presence of the deformity.
Fragmentary Predynastic skeleton have been described from the cemetery at
Badari with a normal shaped cranium both in size in shape. In contrast, however,
the radii and ulna are short and robust, a characteristic of achondroplasia. A second
case consisted of a Predynastic femur and tibia, both with typical short shafts and
relatively large articular ends.

12.3. Childbirth and Anesthesia - Pain or Toil (1846)
When Dr. James Simpson began to use anesthesia in child-birth in 1846, a religious
furor arose against its use. For many people, including many physicians, Genesis
chapter 3, verse 16, implied that childbirth had to be a painful process. In 1849, the
editors of one of Canada's medical journals asked Abraham De Sola, Canada's first
rabbi, to give his interpretation of Genesis 3:16 for the benefit of their readers. Using
Hebrew biblical scholars as his source, he wrote that the correct interpretation of
this passage was that with toil or labor shall women bring forth children, rather than
with pain. Therefore, by using anesthesia in childbirth, physicians were not going
against the scriptures or the word of God.

12.4. Cancer (Ancient Egypt to Present)
The ancient Egyptians probably recognized cancerous lesions on the surface of the
body. Hippocrates described cancers of the skin, larynx, breast, inguinal region,
uterus, and vagina. For centuries, the treatments were excision, cauterization,
ointment application and fomentation. The development of anesthesia, antisepsis,
and disinfection, and the discoveries of X-rays and radium in the 19th century,
greatly promoted advances in surgery in the 20th century. At the beginning of the
20th century, it became possible for surgeons to extirpate tumors from previously
inaccessible body interiors, and today surgeons are able to remove affected organ
systems and even entire regions of the body with safety because of advances in
physiology, anesthesia, transfusion, and anti-infective agents. The surgical results
for most gastrointestinal cancers have improved markedly in recent years, only with
pancreatic cancer showing no improvement in results. Drastic extensive surgery has
not led to better results. There is now an expectation that early diagnosis will be



                                         39
possible by using magnetic resonance cholangiopancreatography and cytological
diagnosis of the pancreatic juice.

12.5. Cushing's Disease (1912)
While the pituitary had been known since Antiquity, the adrenals were first described
in 1563. Until Addison's description of adrenal insufficiency in 1855, virtually nothing
was known of their function. Cushing in 1912 described his famous patient with
hypercorticism but assumed it to be a polyglandular disorder. For almost 40 years,
the etiology was disputed, though Bauer early had postulated that hypercorticism
ultimately reflected either primary or secondary adrenal hyperfunction. Though
Krause, Schloffer, Cushing, Hirsch and others early in the 20th century had
introduced pituitary surgery, it was not until 1933 that the first patient with Cushing's
disease had neurosurgery. This therapy did not gain wide acceptance until Gidot &
Thibaut and Hardy pioneered their transsphenoidal procedure. Adrenal surgery was
for many years the treatment of hypercorticism, but prior to the availability of
glucocorticosteroids substitution, this surgical procedure was an extremely perilous
undertaking.

12.6. Deafness, Asylums and Education (19th Century)
Not too long ago deaf children and adults were institutionalized in asylums because
they were often considered mentally impaired or unintelligent. One man who helped
change those attitudes was Thomas Hopkins Gallaudet, who was born in
Philadelphia in 1787. Gallaudet learned sign language at the Institut Royal des
Sourds-Muets (Royal Institute for Deaf-Mutes) in Paris. When Gallaudet returned to
the United States, he and Laurent Clerc opened the first free school for the deaf in
Hartford, Connecticut. This institution, which is still in existence today, is known as
the American School for the Deaf.

12.7. Duchenne Muscular Dystrophy (1806 - 1875)
Guillaume-Benjamin-Amand Duchenne (1806-1875) didn't follow in his father's
footsteps to become a sea captain. Instead, he chose to study medicine in Paris.
We now know him for the disease after which he is named, Duchenne Muscular
Dystrophy (DMD). Duchenne was not the first to describe this most common and
most severe form of the childhood muscular dystrophies. He was, however, the first
to study the diseased muscle microscopically after developing his own tool for
muscle biopsy. Afterwards, he provided a comprehensive account of the clinical
features and the pathological progression of DMD. In 1868, he described 13 cases
and by 1870 he had seen about 40. While modern-day diagnoses may be more
technically advanced than in Duchenne's day, DMD remains still a relentless,
progressive disease.

12.8. Diseases of the Ear (324-1453 C.E.)
A considerable number of conservative treatments for many otologic conditions
were used during Byzantine times (324-1453 C.E.). These therapies were especially
based on herbs, animal and mineral substances applied either as eardrops, clysters,


                                         40
poultices, or by using special instruments and apparatus. Among the documented
diseases were otitis, rupture of the eardrum, hemorrhage from the ears, deficiency
of hearing and deafness, vertigo, tinnitus, and earwax. Furthermore, based on early
Byzantine texts, surgical techniques are described for cases of atresia of the
external auditory canal, for defects in or lack of the pinna, and for removal of foreign
bodies and fleshy tumors. Some of the earliest hearing aids were also identified.
Based on original works of Byzantine writers, it is evident that numerous treatments
and surgical techniques relating to otology were practiced. These were derived not
only from compilation of knowledge obtained from the ancient Greek medical
sources, a considerable part of which are now lost, but also enriched by Byzantine
physicians' personal experience. This knowledge influenced medieval European
medicine and, through it, that of the rest of the world.

12.9. Eclampsia (Ancient Greece to Present)
Eclampsia, accompanied by coma and convulsions, is one of the most dangerous
complications of pregnancy. This condition was known to the ancient Greeks, who
named it eclampsia. Prior to the 18th century, the term eclampsia was used only to
refer to the visual phenomena which accompanied the neurologic aspects of the
syndrome. Rayer's landmark contribution (1839-1841) provided evidence for renal
involvement with the observation of protein in the urine of pregnant, edematous
women. Lever (1843) reported finding proteinuria in eclampsia and concluded that
disappearance of proteinuria after delivery was evidence that eclampsia was
different from the proteinuria of Bright's disease (Richard Bright, MD - 1789-1858).

12.10.    Glandular Therapy (19th Century)
The emergence of new medical science in the mid-19th century was usually greeted
with derision by "practical men" who saw their academic colleagues as elitist
intellectuals, whose work bore little or no relation to the rough-and-tumble aspects of
patient care. This schism, which was nowhere greater than in the field of
endocrinology, widened in 1891 when a myxedematous patient was dramatically
restored to health after the administration of a thyroid extract. On the one hand,
academicians-who saw this result as a triumphal example of the transference of
laboratory studies to the bedside, were encouraged to pursue further studies in
endocrine pathophysiology and pharmacology. On the other hand, medical
practitioners began to believe that crude extracts from glands or other organs, when
prescribed as orally administered mixtures, were effective for the treatment of most
human ailments. The organotherapeutic forces were ably championed by Henry R.
Harrower, MD, a manufacturer as well as a dispenser of organotherapeutic
products. For some years, the claims of the organotherapists remained
unchallenged. Finally, in 1921, Harvey Cushing, pioneer neurosurgeon and
endocrinologist, launched a crushing assault on the purveyors of pluriglandular
therapy. These attacks continued over ensuing years, and organotherapy fell into
disrepute.

12.11.    Heart



                                         41
   12.11.1. History
In human historical thought, the heart was not always considered part of the blood
circulating system. It was only included as a suction pump when Harvey argued that
the heart is actually a compression pump, the central organ of the circulation, and
the only organ responsible for the motion of blood. While the heart was considered
initially as an autonomous pump, it gradually became viewed as subservient to the
needs of the peripheral organs it perfused. Constant properties assigned to the
heart had to be replaced, one after another, by adjustable parameters. Even the
adequacy of the heart as the sole pump has been doubted, an issue that is still
present today.

   12.11.2. Heart Disease (20th Century)
Before 1900, very few people died of heart disease. Since then, heart disease has
become the number one killer in the U.S. Before the Industrial Revolution, most
people made their living through some sort of manual labor and walking was a major
means of transportation. Laundry was scrubbed, stairs were climbed, carpets were
beat, and butter was churned. With the arrival of automation, most manual labor
was either replaced or assisted by machinery. Modern conveniences made physical
activity unnecessary. Along with the change in lifestyle came a change in diet.
Machines were built to homogenize milk, process cheese, churn butter, and make
ice cream. Previously, such high-fat treats had to be made by hand. Fried foods, like
potato chips, hamburgers, and French fries, became staples in many diets. The
combination of a sedentary lifestyle and a rich diet led to an increase in
cardiovascular events. The rate of heart disease increased so sharply between the
1940 and 1967 that the World Health Organization called it the world's most serious
epidemic. Medical science immediately went to work studying heart disease
including its causes and cures. In 1948, a thirty-year study began in Framingham,
Massachusetts. The Framingham Study involved 5,127 people aged 30 to 62 who
showed no signs of heart disease at the baseline visit. Every two years, the
participants underwent a complete physical examination. The Study lasted thirty
years and has provided priceless information about heart disease.

12.12.    Jaundice (Neonatal) (1785 – Present)
In 1785 Jean Baptiste Thimotee Baumes was awarded a prize from the University of
Paris for his work describing the clinical course in 10 jaundiced infants.
Subsequently, in 1847, Jaques Hervieux described very detailed and systematic
pathoanatomical findings of jaundice which in many respects was a landmark study.
Hervieux had autopsy data on 44 jaundiced infants and clinical observations on
many others. A number of his clinical observations such as 1) the essentially benign
nature of neonatal jaundice in most cases, 2) the appearance of neonatal jaundice
during the first 2 to 4 days of life as well as its disappearance within 1 to 2 weeks,
and 3) the cephalocaudal progression of jaundice, are still thought to be accurate
today. Johannes Orth was an assistant to the famous Virchow in Berlin, when he
published the results of an autopsy of a jaundiced term infant in 1875 . The brain
was notable for an intense yellow staining of the basal ganglia, the wall of the third


                                        42
ventricle, the hippocampus, and the central parts of the cerebellum. While the
contribution of Orth was limited to this single case report, in 1903 Christian Schmorl
presented the results of his autopsies of 120 jaundiced infants to the German
Society for Pathology. All of these infants' brains were jaundiced, but only 6 cases
demonstrated a staining phenomenon similar to that previously described by Orth.
Schmorl coined the term kernicterus (jaundice of the basal ganglia) for this staining
pattern.

12.13.    Macular Edema (1856 – 1950)
The occurrence of macular edema was largely unknown prior to the invention of the
ophthalmoscope. One of the first reports on 'Retinitis in Glycosuria', a disease
complex, which today would partly be described as diabetic maculopathy, was
published in 1856 by Jaeger. His observations were confirmed less than twenty
years later by Nettleship in London, and in 1875 Appolinaire Bouchardat from Paris
described fluid and lipid accumulation in the macula which led to a glucose induced
amblyopia. The first pathophysiological hypotheses of fluid accumulation in the
posterior pole were then put forward in 1882 by Tartuferi, who thought the edema
represented swelling of photoreceptor sheaths. In 1896, the Frenchman Nuel coined
the term 'oedeme maculaire' which he had observed in a retinitis pigmentosa
patient. However, it was not until the end of the first World War, that the Swiss
ophthalmologist Alfred Vogt observed macular edema in a variety of other ocular
conditions. Twenty five years later, Bangerter coined the German term 'Zystoides
Makulaodem', and in 1950, Hruby was the first to draw attention to the development
of macular edema after cataract extraction. The ensuing years have seen the
emergence of new concepts regarding the blood-retinal barrier and the paramount
role of its dysfunction in the development of macular edema.

12.14.    Malaria

   12.14.1. Malaria (1880)
In 1880, during a sojourn at Constantine, Alphonse Laveran discovered the
etiological agent of human malaria. During his microscopic observations of the
parasite in freshly collected blood, Laveran's attention was attracted to the
movement of flagellar bodies in the preparations. In 1884, Laveran showed these
flagellated bodies to Pasteur, Roux and Chamberland who all thought that it was
impossible not to recognize a living body in this mass of protoplasm displacing the
surrounding red blood cells with its protruding flagella. As early as 1890, Elie
Metchnikoff established a link between the flagellar bodies of Laveran and the
stealthy stage of parasitic Coccidia infecting the intestinal epithelium of
salamanders. It was the Pasteuriens and a few others scientists like Danilewski and
Pfeiffer who firmly believed that the flagellar forms were indeed a normal stage
during the hematozoan life cycle. In early 1896, P-L Simond joined Metchnikoff's
laboratory and was assigned to study salamander coccidia in order to clarify the
nature of the flagellar bodies. In a very short period of time, Simond clearly
demonstrated that the coccidia had two types of life cycles; one of which resulted in
the formation of flagellar bodies. The sexual reproduction hypothesis of malaria


                                        43
parasites was also formulated independently in 1898 by W. G. MacCallum working
in the United States on Halteridium, a hematozoan infecting crows.

   12.14.2. Dr. John Cropper - Malaria Researcher in Palestine
On 21st November 1916, the Royal Navy Hospital ship Britannic (the sister ship of
the Titanic) was torpedoed near the island of Kea in the Aegean Sea. Captain Dr.
John Cropper, aged 52, was one of 30 people who drowned of the 1100 on board.
Dr. Cropper was born in 1864, at Guisborough, England and obtained his medical
degree from Cambridge University in 1891. In 1895, the Church Missionary Society
sent him on a medical mission to Palestine where his prominent research was in the
field of malaria - the most common and important disease in Palestine during that
period. Dr. Cropper was the first in Palestine who routinely examined slides
microscopically to correctly diagnosed the type of malaria. Dr. Cropper also
suggested antimalarial measures aimed directly at the mosquito vector and paid
attention to ecological aspects such as breeding places and the daily behavior of
adult mosquitoes. Dr. Cropper noted the common antimalarial measurements of that
time, such as covering of wells, planting of Eucalyptus trees to drain swamps and
the routine use of quinine as a preventive medicine, were only partially effective. He
suggested that the only effective measures must be aimed against the larval
mosquitoes and he recommended the use of a sulphur compound in order to
destroy the larvae. Only many years later were those observations recognized as
being correct.

12.15.    Myasthenia Gravis (1892)
One of the earliest papers describing a case of what came to be known as
myasthenia gravis was written in 1892 in the German language by an American,
Herman Hoppe, who at the time was an assistant in the Berlin polyclinic of the
prominent German neurologist, Hermann Oppenheim. At Oppenheim's insistence,
Hoppe published the pathology of a case that Oppenheim had diagnosed during his
life. Hoppe also collected all the reported similar cases and tried to establish a
symptom-complex, for which he was given credit in Oppenheim's great neurology
textbook of 1894. Upon his return to Cincinnati, Ohio, Hoppe's European experience
qualified him as a specialist in nervous and mental diseases. His private practice of
"neuropsychiatry" was his main occupation, but he also volunteered to teach as
Professor of Nervous and Mental Diseases at the University of Cincinnati. In 1901
Oppenheim published the first monograph about what he called "Die Myasthenische
Paralyse (Bulbarparalyse ohne anatomischen Befund)", summarizing 60 cases
described in the medical literature up to that time. Hoppe, on the other hand, wrote
on myasthenia gravis only once again, a review article in 1914 in a Cincinnati
weekly, giving Oppenheim credit for the establishment of the disease as a clinical
entity.




                                        44
12.16.    Pellagra

   12.16.1. Reports in the US (1700’s - 1902)
Pellagra was in existence for nearly two centuries in Europe before being
recognized in the U.S., where it was first reported in 1902. Over the next two
decades, pellagra occurred in epidemic proportions in the American South. Poverty
and consumption of corn were the most frequently observed risk factors. Since the
exact cause and cure of pellagra was not known, a culture of "pellagraphobia"
formed among the public. Patients were shunned and ostracized. The medical
community implicated spoiled corn as the cause of pellagra, which had economic
repercussions for agriculturists. Joseph Goldberger, MD, of the USPHS eventually
solved the secret of the malady: faulty diet. Goldberger was able to prevent and
induce pellagra by dietary modification, a landmark event in the annals of medicine,
nutrition, and epidemiology.

   12.16.2. Civil War – 20th Century
Initially, endemic pellagra (vitamin B deficiency) developed from dietary deficiencies
after the U.S. Civil War. Recognition of the pellagra "epidemic" in the early part of
the 20th century occurred in stages. These stages of disease recognition distorted
impressions of magnitude, rate of spread, and virulence of the pellagra epidemic.
Beginning in 1907, outbreaks were reported in institutions such as mental and
orphan asylums. Initially, cases were misdiagnosed. Eventually, there was only the
recognition of the most severe cases. Existing severe cases came rapidly to medical
attention, thus inflating the apparent rate of spread. These cases had a fulminant
course and a high case fatality. Eventually, milder cases were increasingly
recognized, leading to an exaggerated rate of increase in number of cases and a
decrease in case fatality and apparent virulence. Finally, greater diagnostic
sensitivity resulted largely from a shift in diagnostic thresholds, with loss of
specificity and increase in false positive diagnoses. Finally, although no suitable
diagnostic marker test was developed, diagnosis was ultimately standardized by
development of a workable case definition and by assessment of response to an
effective therapy (nicotinic acid) applied to presumptive cases.

   12.16.3. Pellagra (1914- 1926)
In 1914, pellagra was thought to be an infectious disease. In order to find a cure for
pellagra, Dr. Joseph Goldberger traveled throughout the South observing
employees in hospitals, asylums, and orphanages. Goldberger never "contracted"
the disease and concluded that diet and pellagra were related. He wrote in
September 1914, "No pellagra develops in those who consume a mixed, well-
balanced diet." Carefully controlled dietary studies in orphanages confirmed this
theory and in a classic experiment in a convict camp in Mississippi, Goldberger
produced the disease experimentally by diet. Additional experiments on himself and
co-workers showed that it was impossible to transmit the disease from one person
to another. Goldberger was convinced that the solution lay with chemists and
experimental nutritionists. Foods were analyzed, and Goldberger and his associates
began experimental studies with dogs. In 1926, the pellagra-preventive factor was

                                        45
reported to be a member of the B-group of vitamins. In October 1937, a researcher
at the University of Wisconsin identified nicotinic acid (niacin) as the curative factor
for pellagra. See: Goldberger, Joseph and G.A. Wheeler. The Experimental
Production of Pellagra in Human Subjects by Means of Diet. Washington:
Government Printing Office, 1920. (Hygienic Laboratory Bulletin)

12.17.    Proteus Syndrome: Elephant Man Diagnosed (1884)
Sir Frederick Treves first showed Joseph Merrick, the famous Elephant Man, to the
Pathological Society of London in 1884. A diagnosis of neurofibromatosis was
suggested in 1909 and was widely accepted. There is no evidence, however, of cafe
au lait spots or histological proof of neurofibromas. It is also clear that Joseph
Merrick's manifestations were much more bizarre than those commonly seen in
neurofibromatosis. Evidence indicates that Merrick suffered from the Proteus
syndrome and had the following features compatible with this diagnosis:
macrocephaly; hyperostosis of the skull; hypertrophy of long bones; and thickened
skin and subcutaneous tissues, particularly of the hands and feet, including plantar
hyperplasia, lipomas, and other unspecified subcutaneous masses.

12.18.    Pulse (300 C.E.)
The most important contribution to clinical medicine by Herophilos, a Greek
anatomist living in Alexandria around 300 C.E., was his development of the theory
of the diagnostic value of the pulse. Although the pulse is referred to occasionally by
earlier writers (for example by Aristotle in his Inquiry Concerning Animals), it was
Herophilos' teacher, Praxagoras, who first restricted the pulse to a distinct group of
vessels and held that it could be used as an indicator of disease. Herophilos
corrected his master's teaching on several points, maintaining that the pulse is not
an innate faculty of the arteries, but one they derive from the heart. Herophilos also
distinguished the pulse, not merely quantitatively, but also qualitatively, from
palpitations, tremors and spasms, which are muscular in origin.

12.19.    Scurvy (14th – 20th Century)

   12.19.1. Background
Scurvy, a disease of dietary deficiency of vitamin C, is uncommon today. However,
among diseases, scurvy has a rich history and an ancient past. The Renaissance
period (14th to 16th centuries) witnessed several epidemics of scurvy among sea
voyagers. In 1747, James Lind, a British Naval surgeon, performed a carefully
designed clinical trial and concluded that oranges, lemons and limes had the most
antiscorbutic effect. Eventually, with the provision of lemon juice and lime juice to
the sea voyagers, scurvy became rare at sea. Infantile scurvy appeared almost as a
new disease toward the end of the 19th century and has been attributed to the
usage of heated milk and proprietary foods. Thomas Barlow described the classic
clinical and pathologic features of infantile scurvy in 1883. Between 1907 and 1912,
Holst and Frolich induced and cured scurvy in guinea pigs by dietary modification. In
1914, Alfred Hess established that pasteurization reduced the antiscorbutic value of
milk and recommended supplementation of fresh fruit and vegetable juices to


                                         46
prevent scurvy. Such pioneering efforts led to the eradication of infantile scurvy in
the United States.

   12.19.2. Scurvy - William Stark (1741-1770)
William Stark (1741-1770) was born in England of Scottish parentage, studied
medicine at Edinburgh and London, and obtained his medical degree at Leyden in
1769. He returned to London and undertook dietary studies upon himself. His
experiments were published by James Carmichael Smyth eighteen years later. The
book is the careful description of Stark's twenty-four dietary experiments which
culminated in his death after seven months. He recorded temperature and weather
conditions, exact weight of food and water he consumed, the weight of all daily
excretions, and the way he felt. In the first experiment the diet was bread and water
(31 days). In succeeding experiments he used bread and water and added other
foods one at a time: olive oil, milk, roast goose, boiled beef, fat, figs, veal. He
recorded that after the first two months, the gums of both jaws were red and swollen
and bled when pressed. This was undoubtedly scurvy and contributed to his early
death at age twenty-nine.

12.20.     Sepsis (C.E. 129-1973)
Galen (C.E. 129-199) propounded the notion that all wounds healed by second
intention and the concept of laudable pus became unshakeable for almost 15
centuries. William of Saliceto (C.E. ca 1210-1280) held quite firmly that pus
formation was bad for both wound and patient and proclaimed that wounds should
heal by first intention. The first rational theory of the nature of infection was by
Fracastoro (1478-1553), a physician of Verona who regarded infection as being due
to the passage of minute bodies from one person to another. However, it was not
until Pasteur (1822-1895) that bacteriology took a significant leap forward. The work
of Semmelweis (1818-1865) is notable for his association between bacterial
infection and puerperal fever. Lister (1827-1912) began the modern movement to
control infection with his pioneering work in antiseptic surgery. Other contributions
came from von Bergman (1836-1907; steam sterilization of instruments) and
Halstead (1852-1922; rubber gloves for surgeons). The development of safe
antibacterial drugs has been confined to the 20th century. This was led by Domagk
(1895-1964; sulfonamides), followed by Sir Alexander Fleming (1881-1955), Sir
Howard Walter Florey (1898-1968) and Sir Ernest Boris Chain (1906-1979;
penicillin) and Selman Waksman (1888-1973; actinomycin).

12.21.     Sitophobia (Food Refusal) and Anorexia Nervosa in Victorian
         Asylums (19th Century)
Although anorexia nervosa emerged as a new syndrome in the second half of the
19th century, its clinical picture seemed to be unknown in the psychiatric hospitals
or asylums. In asylum medicine, the commonly used concept of sitophobia (food
refusal) in the insane covered a wide variety of mental disturbances and cannot be
plainly equated with anorexia nervosa. A major difference is the occurrence of
hallucinations and delusions specifically centered around religion and digestion.
Most probably, anorectic patients were not treated in asylums, but at home, in the

                                        47
      doctor's office, or in general hospitals. This pattern may be partly attributed to the
      fact that both patients and doctors were focusing on symptoms of self-starvation like
      emaciation, constipation, and amenorrhea, which were primarily interpreted as
      referring to somatic diseases. Additionally, wealthy families probably preferred
      private care in water-cure establishments, sanatoria, and rest homes to the
      stigmatizing referral of their anorectic child to an asylum. Hence, the fact that late
      19th-century institutionalized psychiatry was only incidentally confronted with
      anorexia nervosa may explain its lack of interest in the emerging syndrome.

      12.22.    Vertigo and Epilepsy (Ancient Times to Present)
      In ancient times, vertigo was closely linked with epilepsy and it was believed to be
      the harbinger of chronic seizures. With the advent of modern scientific study of
      epilepsy initiated by the French in the 18th and 19th centuries, vertigo, not yet
      associated with disease of the inner ear or vestibular connections, assumed a
      specific role in the clinical gradation of seizure entities. It was believed to be the
      mildest form of epilepsy. Later, with the establishment of the conceptual linkage of
      "larval" or "masked" epilepsy with outbursts of violence, "epileptic vertigo" was
      considered the trigger for potentially lethal behavior and thus assumed a much-
      feared reputation. Evidence for this abounds in the medical, legal, and even the
      popular literature at the end of the 19th century. The role of vertigo and its epileptic
      associations occupied the attention of most of the pioneer workers in epileptology of
      that era, and it was finally agreed that as a symptom the inner ear rather than
      epilepsy underlay its causation. Even today, epilepsy and vertigo are conceptually
      associated, sometimes erroneously.

      12.23.    Ulcers (16th Century to 1885)
      Indigestion and heartburn have been described for thousands of years, but it was
      only in the 16th century that peptic ulcer disease was established by autopsy. At
      first, only gastric ulcers were identified. In the 18th century, duodenal ulcers were
      seen, most of which were fatal cases after perforation or hemorrhage. In the 19th
      century, when autopsy became a common and even routine hospital procedure,
      uncomplicated acute and chronic ulcers were found and then correlated with
      symptoms. Thus, our current clinical understanding dates from the 1820s, by which
      time peptic ulcers were being reported in the U.S. It is unclear why gastric ulcers
      were not diagnosed at The Mount Sinai Hospital (NYC) until 1873 and duodenal
      ulcers until 1885. However, after that time both conditions were diagnosed
      frequently, and they rapidly became common and were treated medically and
      surgically.

13.        DISEASES OF LEADERS

      13.1. Was Louis XIV Infected with Parasites?
      Louis XIV, known as the Sun King, came to the throne at the age of 5 and reigned
      for 72 years, from 1643 to 1715. In 1680, a chateau and surrounding lodges were
      built in Marly-le-Roi, near Paris, to serve as a hunting residence for the king and his
      court. Marly-le-Roi was razed during the French revolution, but archeological


                                               48
excavations revealed the site of several latrines. Examination of their sedimented
faecal remains showed that two nematode parasites--ascaris and trichinella--were
particularly widespread. Also found were many well preserved taenia eggs. In some
of the specimens, the characteristic hooks that allow these tapeworms to fix
themselves on the intestinal wall were still distinguishable. Taeniasis was doubtless
caused by the consumption of insufficiently grilled meat, favoured by the nobility.
Another parasite that infested the king's court was Fasciola hepatica, probably
present in watercress and dandelion. Records testify that watercress was
fashionable and was brought from Cailly, in Normandy, and from Orleans. To this
day, Fasciola hepatica parasitosis has not been eradicated in France.

13.2. Hemophilia and Queen Victoria of England (1837-1901)
Queen Victoria, Queen of England from 1837-1901, was the longest reigning
monarch in English history. She established the monarchy as a respectable
institution while it was losing its place as an important part of the British governing
system. Victoria was a carrier of hemophilia, a genetic disease that causes the
patient to have severe hemorrhages. Were it not for Queen Victoria, the marriage of
her nine offspring to other noble houses would not have transmitted the hemophilia
gene throughout European Royalty. One of the most famous heirs was Tsarevich
Alexis, the only son and heir of Nicholas II, Russia's last Tsar.

13.3. What Did George Washington Die From?
After his second term as first president of the United States, George Washington
retired to his Mount Vernon estate in 1796. It was there that he suddenly fell ill and
died in December of 1799 after an illness lasting only 21 hours. His problem was
first diagnosed as quinsy (peritonsillar abscess) and later modified to "Cynanche
trachealis". A review of the signs, symptoms, and clinical course of his fatal illness
suggests that the cause of death was most likely an otolaryngologic emergency
known as "acute epiglottitis."

13.4. King George III and Acute Intermittent Porphyria (1739 – 1820)
Porphyria is a group of different disorders caused by abnormalities in the chemical
steps leading to the production of heme. King George III, King of England during the
American revolution, was afflicted by acute intermittent porphyria, a hereditary
metabolic disorder. The symptoms of this rare hereditary disease include paralysis,
high blood pressure agonizing abdominal pain, manic overactivity, skin rash, red
urine, delirium and psychosis. King George’s porphyria also most likely exacerbated
his metabolic disorders, accentuating his hostilities towards the colonies. The king
played a part in the complex political maneuverings that resulted in the arrival of
William Pitt the Younger as prime minister in 1783. Political stability continued until
autumn 1788, when George III fell ill with acute intermittent porphyria. In 1810,
George suffered a final decline in his mental health and became blind and deaf. He
suffered from short-term memory loss as well as senile dementia. By 1817, George,
now very old and thin, could no longer walk. His only amusements were eating
cherry tarts and striking the keys of his harpsichord. He was often in tears and
sometimes laughed wildly. George had another violent outburst at Christmas 1819,

                                        49
      when he talked continually. Then he began to refuse food and grew weaker. He died
      on 29 January 1820, at age 81

      13.5. Franklin D. Roosevelt (1882 – 1945)
      Although President Franklin D. Roosevelt had been profoundly affected by paralytic
      polio, he overcame great odds to become the president of the United States in
      1935. In the early years of his presidency, he was diagnosed with persistent
      hypertension. He was also treated with digitalis for congestive heart failure. His
      blood pressure shortly before the Yalta Conference (February l945) had grown
      alarmingly high, and it was evident that he had developed cardiac cachexia.
      Cachexia increases with cardiac failure similar to the increased cachectin of chronic
      inflammatory diseases and far-advanced malignancies. This results in the
      acceleration in the patient's metabolism with a wasting syndrome. The patient
      develops anorexia, weakness and weight loss. Churchill and Stalin were able to
      take advantage of Roosevelt at Yalta because of his hypertensive cardiac failure
      and cachexia. Thus, Roosevelt's cardiac cachexia profoundly affected the outcome
      of the Yalta meeting, and the most likely, the course of world history.

14.        ENDOCRINOLOGY

      14.1. Background (19th and 20th Centuries)
      The demonstration by Bayliss (1860-1924) and Starling (1866-1927) that a chemical
      messenger from the cells of the duodenal and jejunal mucosa travels through the
      blood to excite the pancreatic secretions, revolutionized physiology and provided the
      impetus to establish endocrinology as a specialist field in medicine. Together, their
      contributions to physiology covered a vast sphere of knowledge, ranging from
      hormones to the heart and from enzymes to osmotic forces. Every subject that they
      studied was augmented by their efforts, and their lucid scientific writing brought both
      clarity and organization to the field of physiological endeavor throughout the world.
      Both contributed in a very definite way to crystallizing physiology into a rigorous
      scientific discipline and their respective texts the "Principles of General Physiology"
      (Bayliss) and the "Principles of Human Physiology" (Starling) established a
      framework of thought that for decades remained the lodestar of physiological
      science. As mentors, they devoted themselves to aspirant physiologists from all
      parts of the world, and their dedication to the activities of the Physiological Society
      in London was legendary. Indeed from 1896, when Starling became secretary, until
      the death of Bayliss in 1924, the two ran this august body in one capacity or another
      for more than a quarter of a century. There is little doubt that the felicitous
      collaboration that led to the discovery of secretin and the introduction of the concept
      of chemical messengers represents an advance that not only revolutionized
      physiological thought but the entire face of clinical medicine.

      14.2. Castrati (16th Century – 1924)
      Under the influence of testicular secretion, the male vocal cords increase in length
      by 67% in adult men compared with prepubertal boys, whereas in the female the
      increase is only 24%. This greater length and an increase in vocal cord mass is


                                              50
responsible for the lowering of pitch of the male voice during puberty. From the late
16th century, castration was carried out in Italy to preserve the unbroken male voice
into adult life, but the high pitch was accompanied by fully grown resonating
chambers and a large thoracic capacity, giving rise to the unique voice of the
castrato. The initial stimulus for the production of castrati came from the Sistine
Chapel in Rome, to provide singers for the complex church music of the time. The
second reason was the coming of opera to Italy at the beginning of the 17th century.
Boys were castrated between the ages of 7 and 9 years, and underwent a long
period of voice training. A small number became international opera stars, of whom
the most famous was Farinelli, whose voice ranged over three octaves. By the end
of the 18th century, fashions in opera had changed so that the castrati declined
except in the Vatican, where the Sistine Chapel continued to employ castrati until
1903. The last of the castrati was Alessandro Moreschi, who died in 1924 and made
gramophone recordings that provide the only direct evidence of a castrato's singing
voice.

14.3. Diabetes Mellitus (1st Century C.E.)
Clinical features similar to diabetes mellitus were described 3000 years ago by the
ancient Egyptians. The term "diabetes" was first coined by Araetus of Cappodocia
(81-133 C.E.). Later, the word mellitus (honey sweet) was added by Thomas Willis
in 1675 after rediscovering the sweetness of urine and blood of patients (first
noticed by the ancient Indians). It was only in 1776, that Dobson firstly confirmed the
presence of excess sugar in urine and blood as a cause of their sweetness. In
modern time, the history of diabetes coincided with the emergence of experimental
medicine. An important milestone in the history of diabetes was the establishment
by Claude Bernard (1857) of the role of the liver in glycogenesis, and the concept
that diabetes is due to excess glucose production. The role of the pancreas in
pathogenesis of diabetes was discovered by Mering and Minkowski in 1889. Later,
this discovery constituted the basis of insulin isolation and clinical use by Banting
and Best (1921). Clinical trials to prepare an orally administrated hypoglycemic
agent ended successfully by first marketing of tolbutamide and carbutamide in 1955.

14.4. Surgery (Prehistoric Times to Present)
Endocrine surgery includes excision of diseased or sometimes normal endocrine
glands and occasionally the transplantation of endocrine tissues. Male castration
was performed for social reasons in prehistoric times, and thyroid operations were
described during the twelfth century. Until the end of the nineteenth century most
operations were undertaken to relieve the local effects of pathologic enlargement of
the thyroid, ovaries, pituitary, and adrenals. With the development of anesthesia,
antisepsis (removal of transient microorganisms from the skin and a reduction in the
resident flora), and effective hemostasis, thyroidectomy for benign, nontoxic goiter
was perfected. Thyroid deficiency followed total thyroidectomy, and thyroid
replacement therapy was developed. Toxic goiter was sometimes relieved by partial
thyroidectomy. After the discovery of hormones in the 20th century, knowledge of
endocrinology increased, and many syndromes of hormonal excess were described.
Surgical results improved with mastery of surgical technique, especially for


                                        51
      operations on the thyroid, parathyroids, and pituitary. Notable advances followed
      adequate resection of thyroid tissue and the use of iodine and antithyroid drugs
      before operation for toxic goiter. The use of cortisone rendered adrenalectomy safe
      for the relief of cancer of the breast and prostate and of Cushing's syndrome. For
      about 40 years, increasing numbers of surgeons have specialized in endocrine
      surgery as a discipline within general surgery, and results of treatment have
      improved greatly.

15.        GENERAL MEDICINE

      15.1. Dr. Philip Barrough (1587) - First Book on Medicine in English
      Philip Barrough was an Elizabethan surgeon and physician who, in 1587, published
      the first book on medicine in the English language. In addition to a comprehensive
      presentation of the overall knowledge of medicine of the time, Barrough devoted
      several chapters to the diagnosis and management of the diseases of the teeth and
      diseases of the mouth and oropharynx. Very little is known about the life of
      Barrough, such as the dates of his birth and death and where he practiced
      medicine. It is curious that despite his major contribution to medicine, and the fact
      that his book went into seven editions, his name is not even mentioned in the major
      histories of medicine, such as those of Garrison, Castiglioni, Major, and Mettler.

      15.2. William Beaumont and Early Studies of Gastric Secretion
      As a young army surgeon stationed on Mackinac Island in Michigan, William
      Beaumont (1785-1853) was asked to treat a shotgun wound. The patient, Alexis St.
      Martin, survived but was left with a permanent opening into his stomach from the
      outside. Over the next few years, Dr. Beaumont used this crude fistula to sample
      gastric secretions. He identified hydrochloric acid as the principal agent in gastric
      juice and recognized its digestive and bacteriostatic functions. Moreover, many of
      his conclusions about the regulation of secretion and motility remain valid to this
      day.

      15.3. Antonio Benivieni (1443-1502)- Trailblazer Pathologist
      Antonio Benivieni (ca 1443-1502) practiced medicine in his native city of Florence
      for over thirty years, and kept methodical records, including brief accounts of a
      score of autopsies. His records were edited after his death, and published as "De
      Abditis...Morborum..Causis." The autopsy accounts are brief, but the book is clearly
      the forerunner of the great pathology texts. Benivieni provided the following
      description of an autopsy: “My kinsman, Antonio Bruno, retained the food he had
      eaten for too short a time and then threw it up undigested. He was most carefully
      treated with every kind of remedy for the cure of stomach trouble, but as none was
      of any use at all, his body wasted away through lack of nourishment till little more
      than skin and bone remained. At last he was brought to his death. The body was cut
      open for reasons of public welfare. It was found that the opening of his stomach had
      closed up and it had hardened down to the lowest part with the result that nothing
      could pass through to the organs beyond, and death inevitably followed." Such
      investigations were interdependent with the revitalization of the study of human


                                             52
anatomy, carried out by dissection of the normal human body as part of medical
education. This revitalization is epitomized by the De Humani Corporis Fabrica,
(1543) of Andreas Vesalius, Professor of Anatomy and Surgery at Padua.

15.4. Henry Ingersoll Bowditch (1808-1892) and Oliver Wendell Holmes (1809-
      1894)
Two Bostonians, Henry Ingersoll Bowditch (1808-1892) and Oliver Wendell Holmes
(1809-1894), went to Paris for advanced medical training. They came home ardent
disciples of Pierre Charles Alexandre Louis, leader of the French school that derived
its eminence from expert auscultation and careful correlation of bedside and
autopsy findings. Both Bowditch and Holmes became leaders in 19th-century
American medicine. Bowditch, a successful practitioner and prolific medical writer,
wrote the first important American text on physical examination and became
America's first specialist in pulmonary disease. He pioneered in the public health
movement, was a charter member and later president of the American Medical
Association, and was an abolitionist and an advocate for equal rights for women in
medicine. Holmes left practice to become a medical educator. As Dean of Harvard
Medical School, he tried unsuccessfully to admit white women and free black men to
the school. Although his greatest fame came as a man of letters, Holmes
considered himself first a physician and medical educator, and was justifiably proud
of his definitive study, "The Contagiousness of Puerperal Fever" (1843).

15.5. Frederick Chopin (1810 – 1849) – Did He Have Cystic Fibrosis?
Frederic Chopin, the greatest Polish composer and pianist, suffered from a chronic
disease. However, both his life and after his death, physicians could not definitively
agree on the diagnosis. Chopin's contemporaries accepted the diagnosis of
tuberculosis, a disease very common in the 18th century. However, descriptions of
new clinical entities over time, have provoked new speculation as to what was the
actual disease Chopin was suffering from. What now seems most tenable is that
Chopin may have had cystic fibrosis.

15.6. Abraham Lincoln and Medical Malpractice (1858)
An improperly healed fracture was the most common reason for the medical
malpractice crisis between the 1830s and 1860s in the United States. As a
practicing lawyer in Illinois, Abraham Lincoln defended physicians in medical
malpractice law suits. One of these was Dr. Powers Ritchey, who was sued for
malpractice in 1855. Lincoln agreed to represent Dr. Ritchey in 1858 as the case
was appealed to the supreme court of Illinois. In the interim, Lincoln defended two
indicted murderers and won acquittals for both. Between the two murder trials,
Lincoln debated Stephen A. Douglas while running for U.S. Senator from Illinois.
Lincoln believed that Ritchey's case was poorly represented in the lower court.
Ritchey's prior attorneys did not file a bill of exceptions to the testimony of the
plaintiff's expert medical witnesses. Lincoln attempted to rebut the allegation of a
lack of reasonable medical care and diligence by Ritchey, and he sought to secure a
new trial for his client. In its decision, the supreme court of Illinois did not find any
error and affirmed the lower court's judgment.

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15.7. Joseph Lister (1827 – 1912)

   15.7.1.   Report 1
Joseph Lister is one of the pioneers of Infection Control. Not only did he reduce the
incidence of wound infection (usually fatal pre-Lister) by the introduction of
antiseptic surgery using carbolic acid, but also he was the first to apply Pasteur's
principles to humans. He showed that urine could be kept sterile after boiling in
swan-necked flasks. He was the first person to isolate bacteria in pure culture
(Bacillus lactis) using liquid cultures containing either Pasteur's solution of turnip
infusion and a special syringe to dilute the inoculum. As a result, Lister can be
considered a co-founder of medical microbiology with Koch, who later isolated
bacteria on solid media. Lister also pioneered the use of catgut and rubber tubing
for wound drainage.

   15.7.2.   Report 2
Joseph Lister (1827-1912) did not discover a new drug but made the link between
lack of cleanliness in hospitals and deaths after operations. For this reason, he is
known as the “Father of Antiseptic Surgery”. As Professor of Surgery at Glasgow
University, he was very aware that many people survived the trauma of an operation
but died afterwards of what was known as “ward fever”. In 1865, after reading about
the work done by Louis Pasteur on how wine was soured, Lister hypothesized that
microbes carried in the air caused the diseases which spread in the wards. People
who had been operated on were especially vulnerable as their bodies were weak
and their skin had been cut open so that germs could get into the body with more
ease. Lister decided that the wound itself had to be thoroughly cleaned. To test his
hypothesis, Lister covered compound fracture wounds with a piece of lint covered in
carbolic acid. Death by gangrene was common after such an accident. His success
rate for survival was very high. Lister then developed his idea further by devising a
machine that pumped out a fine mist of carbolic acid into the air around an
operation. As a result, the number of patients operated on by Lister who died fell
dramatically.

15.8. Nostradamus - Doctor and Prophet (1503 - 1566)
Michel de Nostredame, better known by his pseudonym, Nostradamus, was born in
the small Provencal town of St Remy where his father was a prosperous notary.
From an early age, Nostradamus showed a talent for prophecy and as a student he
was skilled in mathematics and astrology, and learned Greek, Latin and Hebrew.
Both of his grandfathers were court physicians who aided in Nostradamus'
education in medicine and herbal folk remedies, as well as in the "forbidden" arts of
Kabbalah and alchemy. On completion of his medical studies, Nostradamus took to
the countryside with his medical and astrological books and assisted in the care of
victims of the Bubonic Plague. His approach was to prescribe fresh, unpolluted air
and water and clean bedding. He also would have all the corpses removed and the
streets cleaned. Each morning before sunrise, Nostradamus would go into the fields
to oversee the harvest of rose petals which he then would dry and crush into fine
powder. From this he made "rose pills" which patients were advised to keep under

                                        54
their tongues at all times without swallowing them. He was reputed to have saved
thousands from plague in Narbonne, Carcassone, Toulouse and Bordeaux.
Gradually, he became famous for his healing powers and when he returned to
Montpellier to take his doctorate degree, a large crowd gathered to hear him defend
his unorthodox practices. He was awarded his degree and held a place on the
medical faculty for three years before moving on to practice in Toulouse and then in
Agen. Nostradamus died at the age of 66, probably of renal complications of gout.

15.9. James Parkinson - Child Advocate (1755-1824)
James Parkinson (1755-1824), of Parkinson's disease fame, while well recognized
as a pioneer of clinical neurology, was even more famous as a founder of modern
paleontology. Parkinson’s writings, outreach and advocacy for children's health also
characterized him as one whose influence was an important springboard from which
evolved the modern specialty of pediatrics. Parkinson was one of the first to write on
child-rearing practices and in this context antedated Benjamin Spock by 150 years.
Parkinson was a pioneer of child safety and the prevention of childhood trauma. He
wrote of the resuscitation of near-drowned children and of first aid for injured
children. He also described child abuse and the development of post-abuse
hydrocephalus. He described the pathophysiology and pathology of appendicitis in
children, of fatal rabies in children and highlighted the risk of death even when a
biting dog was not clinically rabid. His advocacy for social reform for children's
welfare was pioneering.

15.10.    Louis Pasteur (1822-1895)

   15.10.1. Pasteur and Koch on American Medicine
In the years before the Civil War, American interest in germ theories had appeared
at times of epidemics and persisted to a limited extent in the areas of spontaneous
generation and antisepsis. While few Americans imitated Pasteur’s work on
immunology or studied with him, his work on immunity influenced their faith in the
potential of bacteriology as a solution to infectious disease. Koch's discoveries of
the bacterial agents of tuberculosis and cholera stimulated American medical and
public health interest in bacteriology in a more practical way. Americans learned
Koch's methods by taking his courses and imported them directly into their own
laboratories. An enthusiasm for science and educational reform, coupled with
problems associated with infectious diseases related to urbanization and changes in
agriculture, aided the growth of bacteriology in America.

   15.10.2. Work
Throughout his career, the problems that attracted Louis Pasteur (1822-1895)
almost invariably involved considerations of specificity of structure and/or of action.
Thus, his work on asymmetric crystals showed that chemical form not only specifies
crystalline structure, but affects the affinity of ferments as well. In his studies of
diseases of silkworms, of beer, and of wine, he could microscopically distinguish the
specific agents of disease. From this emerged his concept of the specificity of
species which was in contrast to the nonspecificity of spontaneous generation. From


                                        55
      this came the germ theory of disease. It was in the new field of immunology,
      however, where the manifestations of specificity were most clearly seen. Here,
      Pasteur's vaccines worked because he chose the specific pathogen in order to
      induce a specific immunity. He succeeded each time. But the two most prominent
      Pastorian successors in immunology, Elie Metchnikoff and Jules Bordet, were not
      equally successful. Although each contributed significantly to the birth of
      immunology, each advanced a theory that neglected the principle of specificity.
      Metchnikoff's phagocytic theory of immunity could not survive the demonstrable
      specificity of humoral antibodies, while Bordet's physical adsorptive concept of the
      antibody-cell interaction quickly fell to the demonstration by Paul Ehrlich of the
      stereochemical determination of immunological specificity.

      15.11.    William Prout - Physiological Chemist (1785 - 1850)
      In the early 19th century, the discoveries of new substances in the healthy and
      diseased body spawned a search for chemical explanations for physiologic
      phenomena to guide medical diagnosis and control therapy. William Prout's work on
      the nature and treatment of diseases of the urinary organs established his
      reputation as one of Britain's most distinguished physiological chemists. Prout was
      very skeptical of chemical remedies because of possible side effects, but he
      suggested iodine treatment for goiter. He emphasized that a satisfactory diet should
      include carbohydrates, fats, protein, and water. In 1824, he showed that the acid of
      the gastric juice was hydrochloric acid. Prout applied chemical methods and
      reasoning to physiology and was criticized for his view that the body's vital functions
      could be explained by chemistry. His remedy for lack of progress in animal
      chemistry was for physiologists to become chemists.

      15.12.    Vesalius (1514 - 1564)
      Andreas Vesalius, a native of Brussels, was born into a medical family. He was
      trained in Greek and Latin but also learned Hebrew and Arabic so as to extend his
      potential for learning. In 1537, he was appointed professor of Surgery and Anatomy
      at Padua. It was during his three years at Padua that he produced his greatest
      works. In June 1543, Vesalius published his De Human: Corporis Fabrica. In it, he
      not only wrote that Galen could no longer be regarded as the final authority, but
      described his own extensive studies in anatomy. Versalius not only helped make
      anatomy acceptable, but also made it a required course of study for medical
      students. It was Vesalius who pointed the way to the Renaissance and the future.

16.        GENERAL TOPICS

      16.1. Amputation (Neolithic Times - 1810)
      The amputation of a limb is one of the oldest surgical procedures and has been
      practiced since neolithic times for punitive, therapeutic and ritualistic reasons. As
      early as the first century C.E., Celsus described an amputation. A major step in the
      development of the operative technique was the introduction of an artery forceps by
      Paré during the sixteenth century. However, due to a lack of analgesics and
      narcotics, the procedure had to take only a few minutes, such that the amputation


                                              56
was completed in one cut (i.e., detachment of the skin, muscles, and bone at the
same level). This technique, known as "classic circular cut," was modified several
times. In order to reduce suture tension, Petit recommended that the skin be
transected first and the muscles and bone more proximally ("two-stage circular cut,"
1718); Bromfield suggested that the skin be cut first, the muscles more proximally
and the bone most proximal ("three-stage circular cut," 1773). Lowdham (1679),
Verduyn (1696), and Langenbeck (1810) changed the operative technique in that
they used a soft-tissue flap to cover the bone without tension ("flap amputation")

16.2. Anatomy (980 – 1288)
Modern anatomic knowledge has developed throughout centuries with transfer of
knowledge from generations to generations. Ibn-i Sina (980-1037), Razi (850-923),
Davud El-Antaki (?-1008), Ali ibn Abbas (?-982), Ahmed bin Mansur (14th century),
Semseddin-i Itaki (1570-1640), and Ibn-i Nafis (1210-1288) were all Islamic
physicians who contributed to the understanding of anatomy. Each benefited from
Greek and Roman pioneers, as well as from each other. There are original drawings
of the trachea, lung, and vascular system in Semseddin-i Itaki's and Ahmed bin
Mansur's anatomy texts. Ibn-i Nafis's writings also revealed his awareness of the
pulmonary circulation. Ali ibn Abbas wrote that the pulmonary artery wall had two
layers and that these layers may have a role in constriction and relaxation of this
vessel. He also stated that the pulmonary veins branched together with the
bronchial tree. Ahmed bin Mansur, Ali ibn Abbas, and Ibn-i Nafis each wrote that the
heart has two cavities. They also added that the wall of the septum is very thick and
there are no passages in between.

16.3. Arrow Wounds and the Development of Surgery
Archaic peoples developed considerable surgical skill for extraction of arrows,
including thoracotomy (opening of the chest) and trephination (a technique in which
a circular section of the skull is carved away, leaving a hole in the skull). A classical
Hindu veda describes a variety of extraction methods, and Homer's Iliad introduces
the term iatros, which means "he who extracts arrows." Hippocrates of Kos and
Galen, representatives of the humoral doctrine, both shunned surgical intervention
and considered purulence a drainage of materia peccans (spoiled humors).
Cornelius Celsus was the first to systematically differentiate removal of arrows per
extractionem and per expulsionem. Celsus recommended the spoon of Diocles, an
ancient surgical instrument specially designed for extraction of arrows. Paulus of
Aegina favored rapid extraction, aggressive therapy, and ligature on both sides of a
vessel before extraction efforts. Paulus was the first to describe a special instrument
for the removal of detached arrowheads per expulsionem (propulsorium). In
medieval Europe, the standard of surgery declined drastically. The classical
procedure under the dominant influence of the humoral concept was to await pus
before extraction and to burn the wound with boiling oil and a branding iron. Arab
authors had conserved the knowledge of Celsus and Paulus, and in Europe a
renewal was achieved by Ambroise Pare, who has been called the creator of
modern surgery. The incidence of arrow wounds increased once more in the
American West. Joseph H. Bill, a famous U.S. Army Surgeon preoccupied with


                                         57
arrow wounds, favored rapid extraction and aggressive therapy, and he taught
recruits not to apply traction on the shaft. The principles established by Celsus,
Paulus, Pare, and Bill not only mark important landmarks in the evolution of surgery
but can also serve as the basis for modern treatment of arrow wounds, which still
occur, although on a small scale.

16.4. Chorea St. Vitii (658-739)
In the small town of Echternach in Luxembourg, remnants of chorea St. Vitii can be
found every year when pilgrims gather at the grave of St. Willibrord (658-739) to
take part in the so-called Dancing Procession on Whit Tuesday. Miracles and
healings are reported to have taken place in front of Willibrord's sarcophagus in the
late eighth century. News of the miraculous healings inspired the celebratory
folkdances in Echternach. Willibrord became the patron saint of patients with
movement disorders. Important annual pilgrimages to the grave of Saint Willibrord,
with pilgrims from Gallic and Teutonic provinces, were reported around 1100. The
Dancing Procession is first mentioned in the Echternach city archives in 1497. In
1900, Henri Meige, a neurologist with a special interest in movement disorders,
visited Echternach to observe the annual Dancing Procession. Although Meige was
disappointed with the lack of hysteria, he concluded that the Dancing Procession of
Echternach was not without grandeur. Outbreaks of mass hysteria with a
background of religious fervor, pagan traditions, or superstition are the most likely
explanation for the medieval dancing mania. This view is supported by the religious
motivation behind the present-day Dancing Procession in Echternach, a ritual with
mixed pagan-Christian origins related to Saint Vitus' dance.

16.5. Doctoring as a Profession

   16.5.1.   Ancient Rome 1
As a profession, medicine was more highly regarded in Greece than in Rome. In
Greece, physicians were basically craftsmen, probably enjoying some esteem
among their customers, but not being part of the socio-political elite. Roman doctors
did not fare so well. Many doctors were freed Greek slaves, hence the social
standing of doctors was quite low. Because cure rates were also low, many people
were skeptical or even scornful of doctors. Roman literature contains much about
the reactions of individuals to medicine and doctors. To listen to the Roman authors
is to hear tales of quackery at all levels of society. Sources often describe prevalent
chicanery such as: "Some doctors charge the most excessive prices for the most
worthless medicines and drugs, and others in the craft attempt to deal with and treat
diseases they obviously do not understand." (Gargilius Martialis, Preface, 7).

   16.5.2.   Ancient Rome 2
In ancient Rome there were no licensing boards and no formal requirements for
entrance to the profession. Anyone could call himself a doctor. If a doctor's methods
were successful, more patients were attracted; if not, it was time for another
profession. For example, "Until recently, Diaulus was a doctor; now he is an
undertaker. He is still doing as an undertaker, what he used to do as a doctor"


                                        58
(Martial, Epigrams 1.47). Another example is again from Martial, Epigrams (8.74),
"You are now a gladiator, although until recently you were an ophthalmologist. You
did the same thing as a doctor that you do now as a gladiator." Medical training
consisted mostly of apprentice work. Men trained as doctors by following around
another doctor. For example: "I felt a little ill and called Dr. Symmachus. Well, you
came, Symmachus, but you brought 100 medical students with you. One hundred
ice cold hands poked and jabbed me. I didn't have a fever, Symmachus, when I
called you, but now I do." (Martial, Epigrams 5.9). Plutarch grumbled that
practitioners used all sorts of questionable methods to gain patients, ranging from
escorting the prospective patient home from bars to sharing dirty jokes with him.

16.6. Ephemera (15th –16th Centuries
Among the most valuable medical ephemera of all were the broadsides that were
posted by municipal authorities during the Renaissance to warn of epidemics of
plague, cholera and smallpox. Cardboard signs of various sizes and varied colors
for mumps, meningitis, scarlet fever, diphtheria, etc. were placed in windows of
residences where patients were quarantined. Modern day ephemera, issuing from
government bodies and private groups, will be calling attention to the hazards of
smoking, excessive drinking, sexually transmitted diseases, warning signs for
cancer and other public health problems.

16.7. Epidemiology (1830)
In the 1830s in England, there was a great cultural interest in the collection and
publishing of all kinds of statistics. The Council of the Statistical Society of London
(founded in 1834) commissioned one of its Fellows, Dr. William Farr, to investigate
and prepare a report on the mortality of patients in the county asylums, in
comparison with the mortality in proprietary houses. Proprietary houses were
institutions licensed to care for patients with mental illness (then called lunatics) who
had been ordered to be confined due to their mental condition. Committees of
Parliament had investigated the condition of the mentally ill confined to the asylums
and taken measures to improve their treatment and to correct abuses. Farr collected
data from Hanwell, the Middlesex County asylum opened in 1831, and other
asylums. Data included annual admissions, resident patients, deaths, discharges,
derived years of residence (exposure to risk), and annual mortality rates by duration
and as an aggregate. He used similar data from a contemporary report on a large
number of licensed houses. Farr demonstrated that annual mortality rates were
higher during 0-1.5 years of confinement than at years 1.5-7.5, higher in men than in
women, higher in paupers than in other patients, higher in licensed houses than in
the Hanwell Asylum, and higher in the four large licensed houses than in a collection
of smaller ones.

16.8. Ethics
Ethics codes and guidelines date back to the origins of medicine in virtually all
civilizations. Developed by the medical practitioners of each era and culture, oaths,
prayers, and codes bounded new physicians to the profession through agreement
with the principles of conduct toward patients, colleagues, and society. Although

                                         59
less famous than the Hippocratic oath, the medical fraternities of ancient India,
seventh-century China, and early Hebrew society each had medical oaths or codes
that medical apprentices swore to on professional initiation. The Hippocratic oath,
which graduating medical students swear to at more than 60% of US medical
schools, is perhaps the most enduring medical oath of Western civilization. Other
oaths commonly sworn to by new physicians include the Declaration of Geneva (a
secular, updated form of the Hippocratic oath formulated by the World Medical
Association, Ferney-Voltaire, France) and the Prayer of Moses Maimonides,
developed by the 18th-century Jewish physician Marcus Herz.

16.9. Germans, Celts and Others
Before the Roman conquests, the medicine of the Germans was mainly mystical or
domestic. Demons were expelled from the body and sacrifices were given to
appease the gods. The medicine man Kedfinger would touch the patient with a
finger dipped in the blood of the victim to effect cures. Magic stones, and herbs
collected on special days along with spells were the mainstay of medical care.
Women had a special place in Pre-Roman Germanic medicine. l Tacitus wrote of
the ancient Germans, "Ad Matres, ad coniuges vulnera ferunt, nec illae numerare et
exigere plagus parent (they take their injuries to their mothers and wives, who do
not fear to examine and treat their wounds)." Some groups of women healers were
reported to have supernatural powers. After the fall of the Roman Empire, some
areas that were not under the control of the Christian Church returned to the more
primitive forms of medicine. The Gallo-Celtic peoples used this system until the
monks christianized all of Europe and brought with them Roman-style medicine.
Although mysticism remained, there was more reliance on herbalism and empirical
medicine than before. During the Dark Ages, men completely controlled the practice
of medicine. The office of healer was considered holy and reserved for the caste of
Druids. They controlled medicine as well as science and religion for their people
until the Benedictines and other monks changed them all forever.

16.10.   Hospitals (820 C.E. to 1311)
Just as there was a need in the past for someone to record and keep medical
knowledge, there was also a need for a place where the sick could go to get better.
Both of these needs were filled by the Church. It is recorded that the monastery of
St. Gall (820 C.E.) had a medical herb garden, rooms for 6 sick people, a pharmacy,
and special lodging for a physician. This is probably the first example in Western
Europe of a hospital. The Benedictine monasteries quickly expanded the trend and
soon many monasteries in Europe had attached hospitals. During the 12th and 13th
centuries, many large hospitals were made including several Great London
Hospitals. These were mostly under the control of the Church but as time went on,
some lay institutions arose. Also during the 12th and 13th centuries, orders of
knighthood came about to care for the sick. The Knights of St. John came about
during the crusades. They established their first hospital in Jerusalem and later
founded one in Rhodes in 1311. The Hotel-Dieu in Paris had regular nurses (nuns),
2 people per bed, good ventilation and good waste disposal.



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16.11.    Imaging (1890-1950)
Within weeks of Roentgen's announcement of his discovery of X-rays in January
1890, the news had been broadcast to the world via the telegraph and the popular
press. No internet in those days. Although many properties of X-rays were known by
the turn of the century, practical applications developed only gradually. Physicians
were eager to employ X-rays to capture the exact shape of bone fractures, the
location of foreign objects embedded in flesh and the study of growth abnormalities.
The difficulty of using fragile and balky X-ray equipment, however, hampered the
growth of medical radiology. Only when the Coolidge tube had replaced the
unreliable Crookes tube in 1913 and after nitro-cellulose based photographic film
supplanted glass-plate negatives around 1920 did radiology become attractive to
most physicians. Some applications of X-rays were more serious than others, and
ignorance of the dangers of excess radiation hampered the spread of the new
technology. Fluoroscopy, for example, which substituted a screen of light-emitting
crystals for the photographic plate and thus enabled viewers to seek skeletal
structures and organs in motion was a marvelous diagnostic and teaching device.
Yet beginning in the 1920s, floor-model fluoroscopes were installed in shoe stores
and induced a generation of customers to wriggle their toes and see the bones in
their feet. The serious radiation risk of fluoroscopy only became fully apparent in the
early 1950s.

16.12.    Insanity Plea (1857)
During an 1857 trial, the defense claimed that the accused should be absolved of
willful murder because an overdose of chloroform during surgery induced insanity.
In a rare appearance as a prosecutor, Abraham Lincoln tried the case for the State
of Illinois. Expert medical witnesses testified about the side effects of chloroform and
chloroform-induced insanity. Significantly, Lincoln was not knowledgeable about
medical jurisprudence and overlooked potential sources of evidence and expert
witnesses. Defense lawyers presented an impressive array of physicians to testify
about insanity, about chloroform and about the results of an overdosage during
anesthesia. Considering the state of scientific knowledge at the time, the trial was
notable.

16.13.    Medical Education (19th Century)
By the turn of the 19th century, leaders in the medical profession were fully aware of
the over-production of physicians in a variety of poorly run proprietary schools. By
1904, the American Medical Association had created a permanent Council of
Medical Education that surveyed and rated the nation's schools. By 1910 America's
166 medical schools had been reduced in number to 126. This atmosphere of
national concern for the quality of American medical education prompted the
Carnegie Foundation to commission Abraham Flexner to conduct a comprehensive,
independent study of the nation's medical schools. His 1910 report, "Medical
Education in the United States and Canada," is a classic work typical of the
Progressive era. In a muckraking style, Flexner revealed the discrepancies between
school catalogue descriptions of courses and clinical opportunities and the realities


                                        61
of medical training in schools throughout the nation. Flexner argued strongly for
placement of medical education within the structure of American universities, away
from strict control of practitioners, and he emphasized the need to close
substandard schools. For Flexner, the desired ideal was truly academic training,
with clinical teaching in close geographical association with university science
departments.

16.14.    Medical Thought (19th Century to Present)
Scientific medicine at the beginning of the 19th century was heroic medicine. All
diseases resulted from an excess of fluids, and the cure was to relieve the body of
the excesses through bloodletting and purging. The basic scientific knowledge
necessary to disprove such beliefs was slow to develop in America. The generation
of men like Franklin and Jefferson who dominated the intellectual life of the country
from 1750 to 1800 and who promoted scientific research was largely gone by 1800.
Besides, the country had little time and little use for such aristocrats as it was swept
up in the Age of Common Man. As Tocqueville commented, the combination of
democracy and economic opportunity in the Jacksonian era placed an emphasis on
profitable technology over basic science. As a consequence, medical science based
upon empirical research suffered too. Contributing to the stagnation of scientific
advances in the 19th century was the philosophical movement that dominated
American society-Romanticism. Romanticism came to America from Europe
between 1812 and 1861 as a revolt against the Age of Reason. Rather than rational
empirical thought, Romanticism emphasized feeling, sensitivity, and the
supernatural. Since the scientific community was doing little to improve medicine,
and the public was rebelling against the painful and debilitating treatments of
heroics, a void developed in medical treatment. Lay health reformers and
practitioners, filled with the millennial, democratic spirit, rushed in with "theories" of
their own. Their treatments included water, electricity, manipulation of animal
magnetism, and vegetable compounds. Many of the quackery theories took on
qualities of social reform and religious revivalism to become movements of their
own. It was not until the end of the century that scientific advances began to catch
up with the medical needs of the public. Civil War hospital experiences and the new
theories of bacteriology slowly produced fundamental changes in medical practice.
Medical training adapted to the growing knowledge base of the profession, and by
the end of the century, America was well on its way to having the best medical care
in the world.

16.15.    Midwifery (200 C.E.)
Soranus was a physician who wrote in the early second century about childbirth and
the qualifications of a good midwife. To Soranus, the demands of the profession
required a highly competent woman who is "literate, has her wits about her,
possessed of a good memory, loving work, respectable and generally not unduly
handicapped as regards her senses (i.e., sight, smell, hearing), sound of limb,
robust, and, according to some people, endowed with long slim fingers and short
nails at her fingertips." Soranus also insisted that the midwife be of sympathetic
disposition (though she need not herself have borne a child) and keep her hands


                                         62
      soft, presumably so she would not cause discomfort to either mother or child.
      Soranus reasoned that the best midwives should be literate so that they can be
      knowledgeable about obstetrics and pediatric theory. Soranus also felt that the
      midwife must be free from superstition "so as not to overlook salutary measures on
      account of a dream or omen or some customary rite."

      16.16.    Nursing Standards (19th Century)
      At the beginning of the nineteenth century, a separate team of women called the
      "night watch" was responsible for the night nursing in the London teaching hospitals.
      The night watchers were often the uneducated, and frequently the "scrubbers," or
      charwomen, who cleaned the halls and stairways in the hospitals in the daytime. As
      the century progressed, the expanding capabilities of the new academic medicine
      forced an improvement in the standard of nursing. The difficulty in finding clinically
      experienced nurses who were willing to work nights at an affordable price, however,
      made it possible for the night watchers to remain in the new professionally
      organized hospital long after such unskilled and undisciplined workers had been
      phased out of other areas. By the end of the century when hospitals began rotating
      partially trained probationer, or student, nurses onto nights, the night watchers
      finally disappeared from the teaching hospitals.

      16.17.    Sobriety and Alcohol Consumption (1736 – 1871)
      As early as 1736, the Royal College of Physicians submitted to Parliament a
      representation concerning the excessive consumption of spirituous liquors. No
      further authoritative statement was made for nearly a century, by which time the first
      Temperance and Total Abstinence societies had been formed. The medical
      community was happy to support the call for moderation and a number of societies
      issued declarations signed by local practitioners. However, fear of losing patients
      meant that few doctors supported total abstinence. In addition, alcohol was widely
      used as a therapeutic agent. In spite of this, declarations were issued in 1839 and in
      1847 which were essentially "teetotal" in tone. Most of the declarations were
      reported only in the temperance journals. In 1871 declarations were circulated to
      every doctor on the medical register and publicized in full in all the national
      newspapers. It was signed by the Presidents of the Royal Colleges and by 233
      others. It condemns the "inconsiderate prescription" of alcohol and questioned its
      value as a food or as a medicine.

17.        GYNECOLOGY

      17.1. James Marion Sims, Father of Gynecology
      James Marion Sims is recognized throughout the world as the founder of the field of
      gynecology. Dr. Sims' unparalleled successes placed him in demand as far afield as
      the royal houses of Europe. He counted among his patients Napoleon III's Empress
      Eugenie of France, Scotland's Duchess of Hamilton and the Empress of Austria.
      Early in his career, Sims quickly discovered the need for new techniques and
      thought as medical textbooks had remained unchanged for a hundred years. Sims
      blazed a career of original operations and techniques seldom equaled in medical


                                              63
      history. In 1845, Sims established the first woman's hospital in history in
      Montgomery, Alabama. Later, in New York, he established the Woman's Hospital,
      which became the forerunner and pattern for similar institutions around the world.
      Dr. Sims practiced for several years in Paris and London and accepted invitations to
      perform his unique operations. Several European governments honored him with
      their highest awards. New York claims Sims as its own by virtue of his work and
      death there. South Carolina claims him by reason of his birth in Lancaster, S.C., but
      Alabama was the scene of Sims' early work and his initial successes that were to
      spring him into an honored spot in medical annals.

18.        INFECTIOUS DISEASES

      18.1. Anthrax

         18.1.1.   Haitian Epidemic (1770)
      Until recently, anthrax has been described as a veterinary disease of minor
      importance to clinical medicine. Anthrax is known to cause occasional occupational
      infections in single cases or clusters. Anthrax's potential for rapid and widespread
      epidemic transmission under natural circumstances has not been widely
      appreciated. A little-known 1770 epidemic that killed 15,000 people in Saint-
      Domingue (modern Haiti) was probably intestinal anthrax. The epidemic spread
      rapidly throughout the colony in association with consumption of uncooked beef.
      Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural
      circumstances. Historical information may not only provide important clues about
      epidemic development but may also raise awareness about bioterrorism potential.

         18.1.2.   History (Antiquity to 2002)
      Anthrax, a potentially fatal infection, is a virulent and highly contagious disease.
      Descriptions of this disease begin in antiquity, with the best ancient account being
      by the Roman poet Virgil. During the 19th century, anthrax was the infection
      involved in several important medical developments. It served as the prototype for
      Koch's postulates regarding the causation of infectious disease. The first vaccine
      containing attenuated live organisms was Louis Pasteur's veterinary anthrax
      vaccine. In the 1900s, human inhalation anthrax occurred sporadically in the United
      States among textile and tanning workers, but the incidence of the illness had
      declined dramatically. An outbreak of inhalation anthrax occurred in Sverdlovsk near
      a Soviet military microbiology facility in 1979. This epidemic represented the largest
      documented outbreak of human inhalation anthrax in history. In October and
      November 2001, 22 cases of confirmed or suspected inhalation and cutaneous
      anthrax were reported associated with the intentional release of the organism in the
      United States. An additional case of cutaneous disease occurred in March of 2002.

      18.2. Black Plague

         18.2.1.   General Background (541 – 1970)




                                              64
The first time Bubonic Plague affected Western Europe was in the early Middle
Ages. From 541 to 767 C.E. there were no fewer than 15 outbreaks in southern
Europe. Plague then disappeared from Europe for some seven centuries but came
back with a vengeance in 1347, this time by way of the Mediterranean. Plague
ravaged the entire continent for five years, resulting in a serious demographic
depression. From then on until 1722, Plague remained endemic to Europe,
periodically undermining its economy. These epidemics were major determinants of
medieval history, but their study has not been completed to this day. It was not until
the 1970s that archeo-zoologists finally discovered that the black rat had indeed
been present in Europe since Roman times. Further extensive research revealed
that the rat population had gradually grown from a fairly restricted one in the early
Middle Ages to a significant one in the 11th and 13th centuries. The rodents spread
along the major highways explaining the very different geographical impact of the
various Plague epidemics of the early and late medieval periods. However, the
mystery of the exact mechanisms by which plague spread has still not been entirely
elucidated, since the Asian rat flea, Xenopsylla cheopis, whose role as vector was
demonstrated by P. L. Simond, could not have survived in the temperate European
climate. Thus, the question of the European vector is still left hanging: was it a
human or a rat flea? Was the rat a propagator or simply an initiator?

   18.2.2.   The Black (Bubonic) Plague of 542
In 542 C.E., a plague struck Constantinople that was so overwhelming, it changed
the face of history forever. At its height, the daily death toll may have reached
10,000 or more. The final death count is not known, but some historians feel that it
may have reached into the upper hundreds of thousands. Much of the information
that is known about this plague comes from Procopius, the legal advisor to the
general Belisarius. The disease was first noticed in Pelusium, an Egyptian harbor
town, which was infected with a huge rat problem. It then ripped through Alexandria
on its northern invasion towards Syria and Palestine. Procopius wrote "From there it
seemed to spread all over the world, this catastrophe was so overwhelming that the
human race appeared close to annihilation." All victims appeared to experience
similar symptoms. "They had a sudden fever, some while sleeping, some while
walking, and others while engaged without any regard of what they were doing."
Soon after, the symptoms would escalate into a type of swelling. The abdomen,
armpits, thighs, and ears were the most common body parts affected. The lymph
glands were also commonly affected. They were called buboes and for this part of
the body the illness was named. Just as the disease seemed to be at its peak, it
disappeared. The plague, however, held on to life. It would attack again in the 14th
century with such fury that it would earn a new name -- Black Death.

   18.2.3.   Bubonic Plague (1348)
The coming of the Black Death, when in just two years perhaps one third to one half
of Europe's population was destroyed, marks a watershed in Medieval and
Renaissance European History. Bubonic plague (Yersinia pestis) had been absent
from Western Europe for nearly a millennium when it appeared in 1348. The
reaction was immediate and devastating. Up to two thirds of the population of many


                                        65
of the major European cities succumbed to the plague in the first two years. In the
wake of the first infestations there were attacks on women lepers and Jews who
were thought either to have deliberately spread the plague or, because of their
innate dishonor, to have polluted society and brought on God's vengeance. The
recurrence of plague also affected the general understanding of public health.
Beginning in Italy in the 1350s there were new initiatives aimed at raising the level of
public sanitation and governmental regulation of public life. And, finally, by the
sixteenth century a debate over the causes of plague spread in the medical
community as old corruption theories inherited from Greece and Rome were
replaced by ideas of contagion.

   18.2.4.   The Great Plague 1665
Bubonic Plague was known as the Black Death and had been known in England for
centuries. It was a ghastly disease. The victim's skin turned black in patches and
inflamed glands or 'buboes' in the groin combined with compulsive vomiting, swollen
tongue and splitting headaches made it a horrible, agonizing killer. The plague
started in the East, possibly China, and quickly spread through Europe. Whole
communities were wiped out and corpses littered the streets as there was no one
left to bury them. It began in London in the poor, overcrowded parish of St. Giles-in-
the-Field. It started slowly at first but by May of 1665, 43 had died. In June 6,137
people died, in July 17,036 and at its peak in August, 31,159 people died. In all,
15% of the population perished during that terrible summer. Incubation took a mere
four to six days and when the plague appeared in a household, the house was
sealed, thus condemning the whole family to death. These houses were
distinguished by a painted red cross on the door with the words, “Lord have mercy
on us”. At night the corpses were brought out in answer to the cry,' Bring out your
dead', put in a cart and taken away to the plague pits. One pit, called the Great Pit
was at Aldgate in London, and another was at Finsbury Fields.

   18.2.5.   China (1330s)
In the early 1330's an outbreak of deadly bubonic plague occurred in China. Since
China was one of the busiest of the world's trading nations, it was only a matter of
time before the outbreak of plague in China spread to western Asia and Europe. In
October of 1347, several Italian merchant ships returned from a trip to the Black
Sea, one of the key links in trade with China. When the ships docked in Sicily, many
of those on board were already dying of plague. Within days the disease spread to
the city and the surrounding countryside. The disease struck and killed people with
terrible speed. By the following August, the plague had spread as far north as
England, where people called it "The Black Death" because of the black spots it
produced on the skin. A terrible killer was loose across Europe, and Medieval
medicine had no treatments. In winter the disease seemed to disappear, but only
because the fleas, which were transmitting the disease, were dormant. Each spring,
the plague attacked again. In under five years (1347-1352), 25 million people, 1/3 of
Europe's population, were dead.

18.3. Chagas Disease


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   18.3.1.   Chagas Disease
Human Chagas disease, transmitted by the reduviid bug, is perhaps a purely
accidental occurrence. As humans came into contact with the natural foci of
infection, primarily in Central and South America, they might have become infected
as a single addition to the already extensive host range of Trypanosoma cruzi that
included other primates. Thus began a process of adaptation and domiciliation to
human habitations through which the reduviid bugs had direct access to abundant
food as well as protection from climatic changes and predators. Studies have now
been performed using a specific polymerase chain reaction of T. cruzi DNA obtained
from mummified human tissues. Results have shown a positive diagnosis of Chagas
disease in a series of 4,000-year-old Pre-Hispanic human mummies from the
northern coast of Chile. The area has been inhabited at least for 7,000 years, first by
hunters, fishers and gatherers, and then gradually by more permanent settlements.
The studied specimens belonged to the Chinchorro culture, a people inhabiting the
area now occupied by the modern city of Arica. Members of the Chinchorro culture
were essentially fishers with a complex religious ideology. This accounts for the
preservation of their dead in the way of mummified bodies, with further
enhancement by the extremely dry conditions of the desert. Chinchorro mummies
are, perhaps, the oldest preserved bodies known to date.

   18.3.2.   Chagas Disease in Mummies 9,000 Years Ago
Tissue specimens from 283 principally spontaneously (naturally) desiccated human
mummies from coastal and low valley sites in northern Chile and southern Peru
were tested with a DNA probe directed at a kinetoplast DNA segment of
Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups
represented in the sample, ranged from approximately 9,000 years B.P. (before
present) to the time of the Spanish conquest, approximately 450 B.P.. Forty-one
percent of the tissue extracts, amplified by the PCR, reacted positively (i.e.,
hybridized) with the probe. Prevalence patterns demonstrated no statistically
significant differences among the individual cultural groups, nor among subgroups
compared on the basis of age, sex, or weight of specimen tested. These results
suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably
well established at the time that the earliest humans (members of the Chinchorro
culture) first peopled this segment of the Andean coast and inadvertently joined the
many other mammal species acting as hosts for this parasite.

   18.3.3.   Chagas Heart Disease
Chagas heart disease is endemic in 21 countries with approximately 100 million
people at risk. It is the most common cause of myocarditis in the Americas and is
recognized to have existed for more than 4000 years (isolated from mummies).
Chagas disease was discovered during the search to find a cause for the
overwhelming deaths occurring in Brazil in the late 18th century. Physician Carlos
Chagas discovered Trypanosome minasense in 1908 while researching on malaria.
Subsequently, the existence of the barbeiro triatomine (insects bites on the face),
the isolation of the Trypanosome cruzi in the triatomine and the first human


                                        67
description of a disease in a 9-month-old child depicted the existence of a new
human trypanosomiasis. Chagas named the trypanosome species after his
colleague and mentor Oswaldo Cruz. In subsequent papers, Chagas described the
morphology and evolutionary cycle of the trypanosome and the clinical features of
the disease, including involvement of the heart. Never before or since, has one
physician fully characterized a disease from its grass roots to the clinical forms more
or less all by himself.

18.4. Cholera

   18.4.1.   Cholera and the Public Health (1854)
The 1854 English cholera outbreak led to reform of Victorian public health
legislation, including implementation of the Nuisances Removal and Diseases
Prevention Act. The reforms threatened the closure of many factories whose fumes
were considered hazardous to the public's health. One witness to appear before the
Parliamentary committee considering the reforms was Dr. John Snow. Dr. Snow
testified on behalf of the manufacturers threatened by the reforms. Snow stated that
the fumes from such establishments were not hazardous. He contended that the
workers in these factories did not become ill as a result of their exposures, and
therefore these fumes could not be a hazard to the general public's health. Snow
also presented data from the 1854 cholera outbreak as the basis for his belief that
epidemic diseases were transmitted by water, not air. Although the data concerned
cholera, Snow extended the inference to all epidemic diseases. When the
committee's report was published, The Lancet chastised Snow in a stinging editorial.
Nevertheless, parliament subsequently revised the bill in favor of the manufacturers
and passed it into law.

   18.4.2.   Epidemic (1854)
When John Snow undertook the studies of the cholera epidemic of 1854 in London,
he was testing his theory of communicable disease, which had been presented in
1853 at the 80th anniversary of the Medical Society of London. Snow had been
elected orator of the year for 1853 and had spent the better part of a year in
preparation. The presentation was titled, "On Continuous Molecular Changes, More
Particularly in Their Relation to Epidemic Diseases." In the presentation, Snow lays
out a theory which includes recognition that for each communicable disease 1) there
is a distinct and specific cause, 2) that the causal agent is a living organism which is
stable over many generations of propagation, 3) that infection is necessary for
communication to occur, and that 4) the quantity of infectious material transmitted is
increased by multiplication after infection to produce disease manifestations.
Although Snow's theory is similar to Jacob Henle's formulations of a decade earlier,
it is more precise, more comprehensive, and more explicit.

18.5. Disease Transmission

   18.5.1.   From Europe to the Americas (16th Century)



                                        68
With the discovery of the New World, the Europeans who flocked to America
brought infectious diseases with them. During long sea voyages the agents of these
diseases increased their diffusion capacity in a suitable environment. Lack of
hygiene, chronic fatigue, food privation, a diet without vitamins and many persons
kept in confined spaces were the essential features of this environment. Sick
persons, whose health conditions worsened during the journey to the New World,
carried the germs of infectious diseases. The first disease to appear in the New
World was smallpox described in hospital records in 1518 in Hispaniola. From there
the disease moved rapidly to Mexico in 1520, exterminating most of the Aztecs. It
then moved into Guatemala and into the territories of Incas from 1525-26, killing
most of them, as well as their King. The second disease, influenza, appeared in La
Isabela, a few years later, causing a heavy epidemic between 1558 and 1559. Other
diseases followed such as yellow fever and malaria. So Europeans and these
invisible and mortal agents caused enormous destruction of American populations.
In fact historians have estimated that beginning in 1500, for only 50 years, the
population of Peru fell from 60 to 10 million; and in Mexico, in one century, the
populations fell from an initial 10 million to only 2 million.

18.6. English Sweating Disease (1485 – 1551)
A rapidly fatal viral infectious disease appeared in England in 1485. It persisted for
the summer months and disappeared as winter approached. This pattern of
infection re-appeared in 1508, 1517, 1528, and finally in 1551, and never returned.
The epidemic had no respect for wealth or rank, and predominantly attacked males
between the ages of 15 and 45 years of age. The incubation period was very short
and the outcome normally fatal. The symptoms of acute respiratory disease and
copious sweating were characteristic, providing the name 'the English sweating
disease'. It was never in the big league of killer epidemics, such as plague and
influenza, but its pockets of instant lethality in communities gave it a special sense
of horror. The infective cause of this disease remained a total mystery until it was
compared with Hantavirus pulmonary syndrome (HPS) in 1994. While there is a
close resemblance, HPS does not completely match the English sweating disease
and positive identification of a possible rodent carrier for the latter has not been
established.

18.7. Flu

   18.7.1.   Spanish Flu of 1918
The devastating influenza pandemic known as 'Spanish flu', which killed at least 20
million people all over the world in 1918, was responsible for the first bitter blow
inflicted on the field of bacteriology, which had been fortified by the series of
resounding successes in identifying the pathogenic agents of terrible diseases such
as anthrax, cholera, tuberculosis, plague, and syphilis. Based on the Pasteur
revolution, it was assumed that every infectious disease was caused by a
bacterium. As a result, the scientific community had accepted the theory, put
forward by the German bacteriologist, Richard Pfeiffer, in 1892, that the pathogenic
influenza agent was the bacterium, Haemophilus influenzae. But, while the most


                                        69
appalling epidemic ever to sweep through the world since the 'Black Death' of the
1300s was still raging, the scientific community had to admit that influenza
originated not from a microbe, but from a virus.

   18.7.2.   The 1918-19 Influenza Pandemic in Nigeria
Although virologists are not in agreement on the origins of the 1918-19 influenza
pandemic, it has long been associated with the virulent type A virus. At least 21
million people died from the disease over a 12-month period, becoming one of the
world's worst short-term demographic disasters. The disease was introduced into
Nigeria by passengers and crews who arrived via ship from overseas. Thus, coastal
ports were the primary focus of the diffusion of the disease. Its spread to the
hinterland was facilitated by improvements in transportation technology. Neither
maritime quarantine, nor the isolation of patients checked the spread of the disease.
About 500,000 Nigerians, out of a population of 18 million, died in less than 6
months, and between 50 and 80% of the population was stricken. The over-crowded
urban centers were the hardest hit and, even though pandemic declined almost as
suddenly as it began, morbidity, mortality, and panic adversely affected the
productive capacity of the country. Since the 1930s, virologists have gained much
knowledge about the agents responsible for influenza diffusion, but the disease
remains one of the few plagues to be eradicated. This is partly because of the
exceptional adaptability of influenza viruses, and partly because artificially and
naturally-acquired immunity to influenza are temporary in duration, making
reinfection possible even by the same type or subtype of influenza.

   18.7.3.   Influenza Pandemic - 1918
The 1918 influenza pandemic (the Great Pandemic) caused 40 million deaths
worldwide. The magnitude of this pandemic dwarfed in mortality and morbidity the
pandemics of 1889, 1957 and 1968. In retrospect, much can be learnt about the
source, the possible subterranean spread of virus, and the genetic basis of
virulence. The World Health Organization has urged every nation to prepare a
pandemic plan for the first global outbreak of the 21st century. Prior to the outbreak
of the pandemic between 1915 to 1917, there was both epidemiological and
mortality evidence of early outbreaks of a respiratory disease, called epidemic
bronchitis. Certain of these earlier focal outbreaks occurred in France and in the UK
during the winter months, when influenza was known to be in circulation. During this
time, patients presented with a particular heliotrope cyanosis (blue color) that was
very prominent in the clinical diagnosis in the Great Pandemic. The outbreaks in
army camps at Etaples, France and Aldershot, UK in 1916-1917, caused very high
mortality in 25-35 year olds. Increased deaths from bronchopneumonia and
influenza were also recorded in England.




                                        70
18.8. Fourth Disease (17th Century to Present)
Measles and scarlet fever were differentiated from one another in the 17th century.
By 1881, Rubella was accepted as the third distinct pediatric exanthem (an eruptive
disease). Nil Filatow in 1885 and Clement Dukes in 1894 described two distinct
forms of rubella, and in 1900 Dukes proposed that one of these forms of rubella was
a separate entity which he called the fourth disease. For the past five decades,
fourth disease has been considered a non-entity, perhaps a mild form of scarlet
fever, but certainly not a distinct disease. In 1979 Keith Powell resurrected the idea
of the fourth disease and argued that it was caused by exotoxin-producing
Staphylococcus aureus.

18.9. Head Lice in the Middle Ages
Fleas were not the only blood-suckers to afflict the population in the middle ages.
The Leechbook Collection of Medical Recipes (15th century) suggested a number of
cures for nits in the head (head lice): 1) Make lye of wild nept (bryony, Byronia alba)
and therewith wash your head, and it will destroy them; 2) Take quicklime or piment
(spiced wine), and make powder of them, and mix the powder with vinegar and
anoint the head with it. This destroys them without falling of hair or any other harm;
3) Take seawater or else brine, and wash your head, and that shall destroy them; 4)
Take the juice of a herb that is called blight, and anoint your head with it, and both
lice and nits shall fall away; 6) Take a broad list (strip of cloth) the length of a girdle,
and anoint the one side with fresh grease mingled with quick-silver, and spread on it
the powder of lichen and press on it with your finger so that it sticks firmly to it, and
then fold it together, and sew together the sides. Then wind it in a linen cloth, sew it
together, and wear it henceforth. In Styrre Hyt Well, a collection of 15th century
manuscripts found in Samuel Pepys' library, one recipe claims that to slay lice or
nits, take the herb broom and crush it and anoint them with juice and it will slay
them. Hortus Sanitus, a Venetian book from 1511 shows lice being brushed out of a
man's hair. John Gerard's Herball claims that: cotton-weed or cudweed (Graphalium
or Filago sp.), boiled in strong lees (wine deposits) cleans the hair from nits and lice.

18.10.    Hemorrhagic Fever (1545 – 1576)
In 1545, twenty-four years after the Spanish conquest of the Aztec empire, an
epidemic of a malignant form of a hemorrhagic fever appeared in the highlands of
Mexico. The illness was characterized by high fever, headache, and bleeding from
the nose, ears, and mouth, accompanied by jaundice, severe abdominal and
thoracic pain as well as acute neurological manifestations. The disease was highly
lethal and lasted three to four days. It attacked primarily the native population,
leaving the Spaniards almost unaffected. The hemorrhagic fevers remained in the
area for three centuries and the etiologic agent is still unknown. Four epidemics
occurred in Mexico during the colonial period, the worse being the epidemic of 1576
which killed 45% of the entire population of Mexico.




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18.11.    Leprosy

   18.11.1. Leprosy in South America (19th Century)
As imperialist nations rediscovered leprosy in their colonial world in the late
nineteenth century, physicians from Colombia found endemic leprosy in their own
country. In order to create a national medicine philosophy for the management of
leprosy, the medical community provoked fears by exaggerating the number of
leprosy sufferers. This was done to demonstrate that charities were incapable of
dealing with the problem. The government approved laws of compulsory
segregation of leprosy patients in the 1890s, and in 1897, the international
conference on leprosy, held in Berlin, gave international sanction to this isolation.
Lepers actively resisted segregation as a violation of their individual rights. Dr Juan
de Dios Carrasquilla experimented with sero-therapy to cure leprosy, and claimed
that the flea was its agent of transmission. Carrasquilla battled segregation and
proposed instead a hygienic program to improve environmental living conditions.
Unfortunately, his approach was defeated. When the early twentieth century saw the
consolidation of the Colombian state, modernization of the country became a
national priority. The government started to enforce the segregation of lepers, who
were confined within an area circumscribed by a sanitary cordon. This strategy was
a failure as patients resisted segregation.

   18.11.2. Leprosy in NY (2004)
This week we received the following note from our good friend and colleague, Jeff
Laskin, Ph.D. (UMDNJ) concerning last week's article on Leprosy in South America.
"I read with interest the history of medicine note on Leprosy in the On Target
Newsletter. One of my good friends (Bill Levis) just retired from running the Leprosy
(Hansen's Disease) clinics in NYC; although he still treats patients at NYU. Its
surprising as to how many Leprosy patients there currently are in NYC (over 1000;
all but one, Caribbean immigrants). The current thoughts towards new treatments,
such as thalidomide, are quite intriguing. The same kind of Leper colonies that were
in Colombia, SA, were also in the NYC area. There is an island (Penekese Island) in
the Elizabeth Island chain just north of Long Island that served as a 'turn of the
century' leper colony. When I visited the Island, the remnants of the colony were still
evident in the way of decaying farmhouses and an old cemetery."

18.12.    Medieval Household Pest Control
A 15th century English Leechbook (collection of medical recipes) suggests the
following "traps": 'For fleas and lice to slay them, take horsemint and strew it in your
house, and it will slay them' or 'Take the juice of rue and anoint your body with it' or
'Take gorse and boil it in water, and sprinkle that water about the house, and they
will die. Palladius (5th century) recommended bring fleas to a sticky end on surfaces
which were often sprinkled with oil dregs. John Gerard's Herball makes the following
claims for: Fleabane (Erigeron sp.) 'burned where flies, gnats, fleas or any other
venomous things are, doth drive them away' Fleawort (Plaintains or Plantago sp.)
'some hold that the herb strewn in the chamber where many fleas be, will drive them
away, for which cause it took the name Flea wort: but I think it is rather because the

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seed does resemble a flea so much, that it is hard to discerne the one from the
other'; Willow herb (Primilaceae or Lysimachia sp.), 'it is reported that the fume or
smoke of the herbe burned doth drive away fleas and gnats and all manner of
venomous beasts'.

18.13.    Scarlet Fever Epidemics (1848 –1900)
Annual deaths from scarlet fever in Liverpool, UK during 1848-1900 have been used
as a model system for studying the historical dynamics of the epidemics.
Mathematical models have been developed which include the growth of the
population and the death rate from scarlet fever. Time-series analysis of the results
shows that there were two distinct phases to the disease. The first phase occurred
between 1848 and 1880. During this time there were regular epidemics (wavelength
= 3.7 years) consistent with the dry conditions in winter. There is also evidence that
a rise in wheat prices affected women in pregnancy, resulting in increased
susceptibility to their children. The second phase occurred between 1880 and 1900.
During this phase there was a falling endemic level with fewer epidemics. This
period was associated with improved nutritional levels.

18.14.    Lyme Disease and Erythema Migrans (1909 to Present)
The documented history of erythema migrans dates to 1909, when Arvid Afzelius
described a case of this skin lesion at a dermatologic meeting in Sweden. Afzelius
felt that the eruption was likely produced by the bite of a tick. Lyme disease is now
the most common tickborne infection in the United States. Its natural course has
been divided into three clinical stages. The infection begins with a rash and flulike
symptoms and may progress after days to weeks to a disseminated stage and in
months to years to a late stage. There is little information (except erythema migrans)
about the clinical features of the illness that is specific for Lyme disease. The initial
description of Lyme arthritis appeared in 1977, and a number of the patients
described in this series developed a rash thought to be erythema migrans. Four
years later, Burgdorfer discovered the presence of spirochetes (subsequently
named Borrelia burgdorferi) in ticks from an endemic locus of Lyme arthritis and
determined this to be the causative organism of the disease.

18.15.    Tick-Borne Diseases (1889 to Present)
The cause of Texas fever in cattle, which is characterized by lysis of erythrocytes
leading to anemia, icterus, hemoglobinuria, and death, remained unsolved for many
decades. From 1889 to 1893, Theobald Smith and Frederick L. Kilbourne
demonstrated in elegantly conducted experiments how the disease was spread from
cattle to cattle by ticks serving as the vector of transmission. Furthermore, they were
able to identify the pathogen of Texas fever, an intra-erythrocytic protozoan which
Smith named Pyrosoma bigeminum. Today it is recognized that either of two
species of the now renamed genus Babesia, Babesia bigemina and Babesia bovis,
may be involved in Texas fever and that babesiosis is generally transmitted by ticks.
In animals, genera like Boophilus spp., Dermacentor spp. and Rhipicephalus spp.
are possible vectors. The first case of tick-transmitted babesiosis in a human was
reported by Skrabalo and Deanovic in 1957 and occurred near Ljubliana in the small

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town of Strmec, Croatia. In humans, the vectors of most reported cases are ticks of
the genus Ixodes, which are among the most predominant ticks in Austria. Smith
and Kilbourne's work was the first demonstration that ticks transmit disease of any
kind. Furthermore, by proving that ticks carry Babesia microti--which causes
babesiosis in animals and humans, this is the first account of a zoonotic (animal to
human) disease and the foundation of all later work on the animal host and the
arthropod vector.

18.16.    Tuberculosis

   18.16.1. Gold Therapy For Tuberculosis (1920)
Gold compounds were introduced for the treatment of tuberculosis based initially on
the reputation of Robert Koch, who had found gold cyanide effective against M.
tuberculosis in cultures, but not in experimentally infected animals. Treatment of
pulmonary tuberculosis with these compounds was popularized, particularly by
Danish physicians, in the mid-1920s, despite consistently negative experimental
results, based on Paul Ehrlich's theories of antimicrobial drug effects. Difficulties in
the design of interpretable clinical studies were soon recognized but also generally
ignored, thus permitting data to be interpreted as favorable to antituberculous gold
therapy. Eventually toxicity was considered to outweigh the alleged therapeutic
benefit of all gold compounds. This resulted in their discard shortly before the
introduction of streptomycin therapy.

   18.16.2. History
Tuberculosis (TB) since time immemorial has inflicted most miseries in mankind. In
ancient times TB was called by many names but the modern one comes from the
word 'tubercle'. TB, also known as Pott's disease, was widely prevalent among
Egyptians in 3700-1000 B.C.E.. Hippocrates (460-377 B.C.E.) recognized the
symptomatology of TB. The name tuberculosis was first used by Lanneac and Bayle
in early 19th century. Robert Koch in 1882 discovered the tuberculosis bacillus and
Calmette and Guerin laid the foundation BCG vaccination. In 1943, chemotherapy
for TB began with the advent of streptomycin followed by PAS in 1946 and then INH
in 1951.

18.17.    Treatment
Tuberculosis (TB) is today a health priority in Asia, Africa, and South America and is
a re-emerging social disease in the Western World. While the pharmacological
therapy of TB is well established, preventive measures are still under-powered and
under-estimated. Current failures in the prevention of tuberculosis are even more
surprising considering that, already a century ago a comprehensive preventive of
defense against TB had been designed by clinicians and health care managers
such as Enrico Pieragnoli. Pieragnoli was an Italian physician who lived in Florence
between the 19th and 20th century, and who, after many years of accurate planning,
succeeded in 1906 in opening the first Italian TB preventive center. Pieragnoli
considered it his mission to fight against TB, a public enemy that was to be defeated
using the weapons of global prevention; Pieragnoli had crystal clear concepts of


                                         74
      prevention, of the predisposing factors to the disease, and of the need for
      aggressive treatment. He established his preventive institute with two main aims:
      the modification of the individual substratum in which the germs grew and the
      removal of contagion. The prophylactic and diagnostic accuracy of his preventive
      institute are shown in a number of clinical documents containing objective body
      measurements (height, weight, thoracic circumference), quantitative clinical
      comparisons (intra-and inter-subjects) and field epidemiology.

      18.18.    Typho-Malaria Debunked (19th Century)
      Early in the history of medicine, physicians had a difficult time differentiating acute
      febrile illnesses without localizing signs. Typhoid fever and malaria share common
      features, which caused diagnostic problems during the 1800s. Physicians even
      introduced a new term, typho-malaria, a testimony to their diagnostic confusion. Sir
      William Osler (1849-1919), consummate clinician and careful observer, had vast
      experience with typhoid fever and malaria. Osler was easily able to discern between
      the key features of both of these infections. He also relied on fever patterns to
      clearly differentiate typhoid fever from malaria. Osler is credited for debunking the
      term typho-malaria. His clinical description of typhoid fever remains unsurpassed.
      Clinicians still can benefit greatly from reading Osler's clinical description of typhoid
      fever.

      18.19.    Yellow Fever and Politics (1821 -1823
      The outbreak of yellow fever that struck Barcelona, Spain in 1821 followed a typical
      pattern for the times. What happened was that a ship from Cuba introduced the
      disease in the port of Barcelona. The epidemic quicky spread to the poor suburbs,
      and finally to the center of the city. It was assumed that at least 20,000 inhabitants
      died from the scourge, a sixth of the total population of 120,000. French authorities
      promptly took emergency measures at land and maritime borders by locking French
      ports to Catalan vessels. The quarantine line along the Pyrenean border was
      controlled by an army of 15,000. A French medical team including six physicians
      and two nuns was sent to Barcelona to provide assistance. Long after the epidemic
      receded, the Pyrenean quarantine line was maintained by the French for a hidden
      political purpose (i.e. Paris wished to contain Spanish Liberalism, a "revolutionary
      pest"). French troops engaged in the so-called quarantine line were used in 1823 to
      invade the Spanish kingdom. French physicians returning to Paris were celebrated
      as heroes and benefactors of mankind although they had not provided any serious
      contribution to the therapy or the epidemiology of yellow fever. This unexpected
      manifestation of nationalism was welcomed and encouraged by the government of
      Louis XVIII who felt himself threatened by the liberal opposition.

19.        MESOPOTAMIA

      19.1. Dental Disease in Ancient Mesopotamia (2000 B.C.E.)
      Sumer, an empire in ancient Mesopotamia (southern Iraq), is well known as the
      cradle of our modern civilization and the home of biblical Abraham. An analysis of
      skeletal remains from cemeteries at the ancient cities of Ur and Kish (circa 2000


                                               75
      B.C.), shows a genetically homogeneous, diseased, and short-lived population.
      These ancient Mesopotamians suffered severe dental attrition (95%), periodontal
      disease (42%), and caries (2%). Many oral congenital and neoplastic lesions were
      noted. During this period, the "local dentists" knew only a few modern dental
      techniques. Skeletal (dental) evidence indicates that the population suffered from
      chronic malnutrition which was probably caused by famine. This is substantiated in
      historic cuneiform and biblical writings, geologic strata samples, and analysis of
      skeletal and forensic dental pathology. These people had modern dentition but
      relatively poor dental health. The population's lack of malocclusions, caries, and
      TMJ problems appear to be due to flat plane occlusion.

      19.2. Hebrew Medicine
      Hebrew medicine was mostly influenced by contact with Mesopotamian medicine
      during the Assyrian and Babylonian captivities. Disease was considered evidence of
      the wrath of God. The priesthood acquired the responsibility for compiling hygienic
      regulations, and the status of the midwife as an assistant in childbirth was clearly
      defined. Although the Old Testament contains a few references to diseases caused
      by the intrusion of spirits, the tone of biblical medicine is modern in its marked
      emphasis on preventing disease. The Book of Leviticus includes precise instructions
      on such varied subjects as feminine hygiene, segregation of the sick, and cleaning
      of materials capable of harboring and transmitting disease. Circumcision, the
      surgical removal of the foreskin on the male's penis, is the only surgical procedure
      clearly described in the Bible. However, other common medical practices included
      wounds dressed with oil, wine, and balsam. The leprosy so frequently mentioned in
      the Bible, is now believed to have embraced many skin diseases, including
      psoriasis.

20.        MIDDLE AGES

      20.1. Dark Middle Ages (400-800 C.E.)
      Medicine in the Dark Ages (400-800 C.E.) As the Roman empire failed from the 2nd
      and the 4th centuries C.E., there was a need for a place where the sick and
      wounded could go to seek solace. The one institution left to provide healthcare was
      the Church of Rome. Literary medicine found a haven in the churches and cloisters.
      Here information survived and records could be kept. Another reason why medical
      practices of the Dark Ages were centered in the churches and cloisters was that
      they contained the hospitals. During the Dark Ages, lists of medical herbs were kept
      by the monks and persons needing medical help would go to them. St. Benedict
      (born 480 A.D.) encouraged monastic medicine at the hospice he founded at
      Montecassino. Cassiodorus (490-585?) encouraged monks in his monasteries to
      study medicine. He not only encouraged the teaching of herbs and medication but
      also fostered the bonds of Christian thought to its Greco-Roman predecessor. He
      reemphasized the study of Hippocrates, Galen, and others. This seed of learning
      grew over the next several centuries as Montecassino continued to foster medical
      education and to be renowned for its medical advances.



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20.2. High Middle Ages (1200-1400)
The 13th and 14th centuries were times of great growth and development in
medicine. Medical teaching had progressed to the point where university degrees
were required to practice medicine. In 1140, Roger, King of Sicily enforced a law
prohibiting anyone from the practice of medicine who had not graduated. Twelfth
and 13th century Europe gave birth to great universities. The two greatest
universities with medical schools were in Bologna and Montpellier. In Bologna, there
was a medical faculty as early as 1156. Early on, the school was mainly scholastic,
reading and repeating the works of the ancients, without any experimentation. There
were two physicians from the school at Bologna who made great contributions to
medicine. William of Saliceto (1210-1280) was instrumental in setting up a school of
surgery. He recommended the use of the knife instead of the cautery in surgery and
taught that pus in a wound was a bad thing. He sutured severed nerves back
together in surgery and tried to bring the disciplines of surgery and medicine closer
together. Theodoric, Bishop of Cervia advocated the use of wine to clean wounds
and suggested that the noxious compounds commonly used only impeded healing.
He also wrote of narcotics such as opium, mandragora, and others being soaked
into sponges and held over the patients' noses to induce a "deep sleep" during
surgery. Spectacles for the eyes were first documented by Bernard de Gordon at
the end of the 13th century.

20.3. Padua: The Renaissance of Human Anatomy and Medicine
The city and University of Padua have a long tradition and a great reputation in
anatomic studies, dating from the founding of the university in the year 1222. The
background for the development of this culture was represented by the scientific
freedom and political wisdom of the Serenissima Republic of Venice, a liberal and
tolerant state in the midst of a feudal, imperial, and pontifical Europe. During the
second half of the 15th century, the flourishing trade and cultural, social, and
political life of Venice attracted a great number of scientists and students from all
over Europe who contributed to the establishment of Padua as an international
center for culture and the sciences. Vesalio, Fabrizio d'Acquapendente, and
Giovanni Battista Morgagni represent milestones in the history of anatomy as well
as in medicine and surgery. History shows that anatomy and surgery evolved
together, just as anatomy of the nervous system and neurosurgery developed in
tandem. The tradition of neurosurgery in Padua is considered one the most
important schools in Italy.

20.4. The Late Middle Ages And Renaissance (1400-)
Knowledge and learning spread far and wide during the 14th century, but this was
only a prelude to the amazing advances to come. The use of guns became more
widespread in battle, therefore, the art of surgery advanced. Wounds were treated
with warm, not boiling oil. Amputations were closed with a skin flap instead of being
cauterized. By the end of the 15th century, with the advent of the printing press,
there was a marked increase in medical literature. Herbals and herbalism were also
more in vogue, the number of hospitals were increasing and cities vied with each


                                        77
      other to have the best hospitals. Plastic surgery was founded in the 16th century.
      Ambroise Pare (1510-1590) was one of the great surgeons of the Renaissance. He
      found that a mixture of eggs, oil of roses and turpentine allowed wounds to heal
      better than scalding oil. His contemporaries discovered the tourniquet and found
      that ligated arteries did better than cauterized ones.

      20.5. Medieval Manuscripts (11th to 15th Centuries)
      To celebrate the return of a long-missing medieval manuscript, the National Library
      of Medicine (NLM) has mounted a small exhibit of medieval manuscripts that date
      from the 11th through 15th centuries and printed books that date from the 15th
      through 17th centuries. The Latin manuscript, "Treatises on Medicine," written in
      England in the 12th century mysteriously disappeared from the Library 50 years
      ago. The manuscript, sometimes known as "Recepta Varia" or "Manuscript 8,
      contains 40 texts by different authors, and typifies medieval attempts to compile all
      medical knowledge. The texts range from guides for diagnosis by pulse and urine, to
      recipes, lists of medical substances, and discourses on blood-letting and surgery.
      The work contains a few magical cures and there are a few references to astrology
      and divination, but the predominant tone is rational. The texts are bound together
      with some hymns and the story of an errant monk whom the Virgin Mary saved from
      eternal damnation. The manuscript is very important because it represents the
      transition between the monastic infirmary and the university faculty of medicine; and
      it marks an intermediate stage between the healing art and bookish science. The
      NLM exhibit also features approximately 25 other books and manuscripts, including
      an illuminated manuscript from 13th-century Oxford, an Arabic text from 1094 (the
      oldest item in the NLM collection), and several copies of Hippocrates' Aphorisms.
      Other treasures in the exhibit include works by physicians who practiced in Salerno,
      Italy, between the 10th and 12th centuries; texts that made up the curriculum in the
      first faculties of medicine; and books that demonstrate the flourishing of medical
      literature in medieval England.

      20.6. Medieval Spain (10th and 13th Centuries)
      The royal burial chamber of what is today the Collegiate-Basilica of St. Isidoro in
      Leon, Spain, was built and remodeled between the 10th and 13th centuries and in
      the 20th century was renamed the Kings' Pantheon. The burial chamber has 13
      royal tombs that were opened in the presence of the Abbot-Prior of the Collegiate to
      enable a group of scientists to obtain all possible information from the royal remains.
      Several samples were sent to the Parasitology Unit of the Animal Pathology (Animal
      Health) Department at the Veterinary Faculty of Leon (Spain). In all the tombs, eggs
      and remains of nonparasitic mites were observed. In a piece of linen cloth from the
      bottom of 1 tomb, an Anoplocephala perfoliata (horse tape worm) egg was found.
      Furthermore, 4 human mummified bodies were found. In 2 of these, those belonging
      to Infantes Maria and Fernando, Ascaris lumbricoides (human nematode worm)
      eggs were found and in the latter, Trichuris trichiura (human whip worm) eggs were
      found.

21.        MIDDLE-EASTERN MEDICINE


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      21.1. Serefeddin Sabuncuoglu - Turkish Surgeon (15th Century)
      Serefeddin Sabuncuoglu (1385-1468 C.E.) was a Turkish surgeon who lived in the
      Ottoman Empire during the fifteenth century, a time of progressive expansion. When
      in his eighties, he wrote Cerrahiyyetu'l-Haniyye, which means Imperial Surgery. His
      book is the first example of an illustrated surgical textbook in the Turkish-Islamic
      medical literature. The importance of his book rests upon the inclusion of color
      miniatures of the surgical procedures, incisional techniques and instruments, all
      drawn by Sabuncuoglu himself. Only three hand-written copies exist, two of which
      were originally written by the author and are currently exhibited in Paris and
      Istanbul. The book was rediscovered in 1936, but some parts of it are still suspected
      to be missing. At present, the book consists of three chapters divided into 193
      known sections. The sections deal with all fields of surgery including ophthalmology,
      and cite relevant Greek, Arabic and Persian textbooks.

22.        NEPHROLOGY

      22.1. History of Kidney Disease (1st Century C.E.)
      The first book on diseases of the kidneys, titled "Diseases of the Kidneys and
      Bladder," was written by Ruphus of Ephesus at the close of the 1st century C.E..
      Little is known of Rufus of Ephesus, who seems to have attained fame and was
      considered an equal of Hippocrates and Galen. He was highly respected and
      extensively quoted by authors of Byzantine, Arabic and Middle Ages medicine. In
      his description of diseases of the kidneys he made a concerted effort to correlate
      structure and function, and to provide a rational explanation of the altered function of
      the kidneys in disease. While the section of his monograph "On Hardening of the
      Kidneys" is brief, it constitutes the first description of morbid and clinical features of
      the end-stage kidneys. Like many of his contemporaries, Rufus wrote several
      monographs on selected topics and organs. That he chose diseases of the kidneys
      as the subject of one of his monographs makes him especially pertinent to the
      history of nephrology.

      22.2. Richard Bright (1789-1858)
      Richard Bright (1789-1858) discovered that edema and proteinuria are linked with
      renal disease. Friedrich Theodor von Frerichs (1819-1885) performed microscopic
      studies on Bright's disease and wrote the first German textbook of nephrology.
      Frerichs conducted clinical and microscopic studies that led him to conclude that
      Bright's disease is a single pathological entity with many possible causes. Frerichs
      identified three stages through which the condition progresses. Although an
      oversimplification, Frerichs' various stages are reflected in the current notion that
      chronic renal disease, irrespectively of its etiology, relentlessly progresses to end-
      stage renal failure with common features of tubulointerstitial fibrosis and tubular
      atrophy. After writing his monograph, Frerichs never touched on renal disease again
      and is actually better known for his contributions to hepatology. Frerichs put the
      study of renal diseases on the map in Germany and made the novel observation
      that chronic renal diseases follow similar morphological patterns despite multiple
      origins.

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      22.3. Homer Smith Father of Nephrology (1895 - 1962)
      From the 1930s until his death in 1962, Homer Smith was considered one of the
      leaders in the field of renal physiology. Smith played a major role in introducing and
      popularizing renal clearance methods, such as non-invasive methods for the
      measurement of glomerular filtration rate, renal blood flow and tubular transport
      capacity. Dr. Smith also provided insights into the mechanisms of excretion of water
      and electrolytes. Smith was also a superb writer of several inspiring textbooks of
      renal physiology that exerted great and lasting influence on the development of
      renal physiology. Smith's intellectual insights and ability for critical analysis of data
      allowed him to create broad concepts that defined the functional properties of
      glomeruli, tubules and the renal circulation. A distinguishing feature of Smith's
      career was his close contact and collaboration, over many years, with several
      clinicians of his alma mater, New York University. So great was Smiths influence
      and preeminence, that Robert Pitts, in his tribute to Homer Smith in the Memoirs of
      the National Academy of Science, stated that Smiths death brought an end to what
      might be aptly called the Smithian Era of renal physiology.

      22.4. Emerich Ullmann - Kidney Transplantation (1861-1937)
      Emerich Ullmann (1861-1937) is the acknowledged pioneer of kidney
      transplantation. In 1902 he performed experiments with auto-, allo-, and
      xenotransplantations in dogs and sheep. In the same year he unsuccessfully tried to
      perform a human kidney grafting by transplanting a pig kidney to a woman with end-
      stage renal disease. Ullmann also conducted many experiments with other organ
      and tissue transplantations. In fact, he should be regarded as the father of intestinal
      transplantation. Furthermore, he systematically investigated skin, testes, ovary and
      bone transplantation. Moreover, he recorded clinical transplantations and in 1914
      wrote a booklet (which in abridged form was published in English) summarizing
      knowledge on the organ and tissue transplantations of his time. Ullmann was an
      extremely innovative surgeon, who introduced various new surgical techniques. Last
      but not least, he was a broadly educated, literary man and an internationally
      renowned art expert and collector.

23.        NEUROLOGY

      23.1. Babinski

         23.1.1.    Background
      In 1896 Joseph Francois Felix Babinski described for the first time the phenomenon
      of the toes. In his first paper he simply described extension of all toes with noxious
      stimulation of the sole of the foot. It was not until 1898 that he specifically described
      the extension of the hallux with stimulation of the lateral border of the sole. Babinski
      was probably not aware at the time that E. Remak, a German physician, had
      previously described the sign. In his third paper of 1903 Babinski concluded that if
      other authors had described the abnormal reflex before him, they found it
      fortuitously and did not realize its semiologic value. Babinski probably discovered it
      by a combination of chance, careful observation and intuition. He also had in mind


                                               80
practical applications of the sign particularly in the differential diagnosis with hysteria
and in medico-legal areas. Several of his observations and the physiopathological
mechanisms proposed by him are still valid today. He realized since 1896 that the
Babinski reflex was part of the flexor reflex synergy. He observed that several
patients during the first hours of an acute cerebral or spinal insult had absent
extensor reflexes. He realized that most patients with the abnormal reflex had
weakness of the toes and ankles. He found a lack of correlation between
hyperactive myotatic reflexes and the presence of an upgoing hallux. He discovered
that not all patients with hemiplegia or paraplegia had the sign. He thought
erroneously that some normal subjects could have an upgoing toe. His dream of a
practical application of the sign has been fully achieved. The motto of Babinski was
Observatio summa lex. Perhaps there is no better dictum in clinical neurology.

   23.1.2.    100 Year Anniversary (1896-1996)
The year 1996 marked the centenary of Babinski's description of the toe responses
(normal and pathological) after stimulation of the sole of the foot. The upgoing toe
response is normal in the 1st year of life and forms part of the flexion synergy of the
leg, which had been known before 1896. Babinski also recognized the relation
between the toe phenomenon (phenomene des orteils) in older children and adults
and dysfunction of the pyramidal system. Neurologists became so fascinated by toe
responses alone that many competing signs were proposed; most of these
consisted of stimuli at other parts of the leg and were actually part of the same-but
temporarily forgotten-flexion synergy. From 1910 to 1915 Marie and Foix and also
Walshe re-emphasized this relationship and pointed out the analogy with the flexion
reflex of the dog that had been extensively studied by Sherrington; the toe
"extensors" shorten the leg and therefore they are flexors in a physiological sense.
The normal (downward) toe response of the toes does not belong to a more
complex movement, although Babinski originally believed this; it is a
monosegmental skin reflex, akin to abdominal reflexes. Babinski correctly predicted
that dysfunction of the pyramidal tract is not synonymous with a lesion, and that this
dysfunction of the pyramidal system is necessary but not sufficient to produce a
phenomene des orteils.

23.2. Brain Surgery (Late Stone Age)
Brain surgery is perhaps the oldest of the practiced medical arts. There is ample
evidence of brain surgery, dating back to the Neolithic (late Stone Age) period.
Unearthed remains of successful brain operations, as well as surgical implements,
were found in France-- at one of Europe's noted archeological digs. And, the
success rate was remarkable, even circa 7,000 B.C.E. But, pre-historic evidence of
brain surgery was not limited to Europe. Pre-Incan civilization used brain surgery as
an extensive practice as early as 2,000 B.C.E. In Paracas, Peru, a desert strip south
of Lima, archeologic evidence indicates that brain surgery was used extensively.
The treatment was used for mental illnesses, epilepsy, headaches, organic
diseases, osteomylitis, as well as head injuries. Brain surgery was also used for
both spiritual and magical reasons; often, the practice was limited to kings, priests



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and the nobility. Surgical tools in South America were made of both bronze and
man-shaped obsidian (a hard, sharp-edged volcanic rock).

23.3. Carotid Artery Compression (18th Century)
Beginning in the late 18th century, facial flushing and bounding carotid artery pulses
during seizures were seen as evidence that seizures resulted from venous
hyperemia (excess of blood; congestion) of the Central Nervous System (CNS).
Consequently, physicians used digital compression of the carotid artery, and later
carotid ligation, to abort seizures. In the early 1880s, New York neurologist James
Leonard Corning (1855-1923) developed several instruments for carotid artery
compression in the treatment of seizures. These devices included a two-pronged,
fork-like instrument (the "carotid fork") for temporary compression as an abortive
treatment and an adjustable belt-like instrument to encircle the neck (the "carotid
truss") for chronic compression as a prophylactic treatment. Corning's uncontrolled
observations suggested that the abortive treatment decreased the duration of
seizures and that the prophylactic treatment decreased the frequency of seizures.
Corning later combined instrumented carotid artery compression with other devices
to decrease cerebral blood flow, including transcutaneous electrical vagal nerve and
cervical sympathetic stimulation. Observed side effects of treatment included
bradycardia (slowing of the heart), dizziness, and syncope (fainting). Corning's use
of instrumented carotid compression and his precocious application of
transcutaneous electrical vagal nerve stimulation were not widely adopted by
neurologists, and these techniques and devices ultimately were abandoned in the
late 19th century.

23.4. Epilepsy

   23.4.1.   Electrical Theory (1873)
John Hughlings Jackson is widely credited with the first electrical theory of epilepsy
(1873). This theory was subsequently confirmed by the experimental studies of
Hitzig and Ferrier. Hughlings Jackson’s views are summarized in his famous
Lumleian lectures to the Royal College of Physicians in 1890. Robert Bentley Todd,
however, had earlier developed an electrical theory of epilepsy, which he presented
in his own brilliant Lumleian lectures to the Royal College of Physicians in 1849.
Todd was influenced by the electrical discoveries of his contemporary, Michael
Faraday, and thought of the brain as having battery like properties that led to the
sudden discharge of electrical energy (nervous force) in epilepsy. Unlike Hughlings
Jackson, Todd was an anatomist and physiologist as well as a physician, and he did
his own electrical experiments in rabbits to prove his theory. There is no mention of
Todd's Lumleian lectures in Hughlings Jackson's later lectures and writings, nor in
those of Hitzig or Ferrier. Todd's remarkable observations and lectures, and his
electrical theory of epilepsy deserve to be drawn to the attention of the medical and
scientific community.

   23.4.2.   Herodotus and Epilepsy



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Herodotus' account of the mad acts of the Persian king Cambyses II contains one of
the two extant pre-Hippocratic Greek references to epilepsy. This reference helps to
illuminate Greek thinking about epilepsy, and diseases in general, at the time
immediately preceding the publication of the Hippocratic treatise on epilepsy. In his
treatise entitled “On the Sacred Disease, Herodotus attributed Cambyses' erratic
behavior as ruler of Egypt to either the retribution of an aggrieved god or to the fact
that he had the sacred disease. Herodotus considered the possibility that the sacred
disease was a somatic illness, agreeing with later Hippocratic authors that epilepsy
has a natural rather than a divine cause. Archaeological evidence, however,
suggests that Herodotus slanders Cambyses, since there is no corroboration that
the Persian king had epilepsy or any other disease. However, the view of epilepsy
as a somatic disease and uncertainty about the cause of madness shows Herodotus
as a transitional figure between supernatural and naturalistic medical theories.

   23.4.3.   Byzantine Emperor Michael IV (11th Century)
Byzantine Emperor Michael IV, Paphlagon (who reigned from 1034 to 1041 C.E.)
suffered from generalized tonic-clonic epileptic seizures. Byzantine historians and
chroniclers have provided detailed clinical descriptions of the seizures. Expressing
popular opinion, nearly all at that time considered his disease to be a demonic
possession that constituted a form of divine punishment for the emperor's adultery
and acts of murder. In contrast, the Emperor's royal entourage euphemistically
attempted to present this condition as a psychic disease. Interestingly, research into
Byzantine medical texts revealed that physicians, from as early as the 4th century,
and following Hippocratic tradition, believed that epilepsy was primarily a brain-
related disorder and based their treatment on this etiological principle. Therefore,
despite the concept then held by well-educated Byzantine doctors who considered
epilepsy a brain disorder, information indicates the deep prejudices of Paphlagon's
social environment.

   23.4.4.   Joan of Arc and Epilepsy
For centuries, romantics have praised, and historians and scientists have debated,
the mystery of Joan of Arc's exceptional achievements. How could an uneducated
farmer's daughter, raised in harsh isolation in a remote village in medieval France,
find the strength and resolution to alter the course of history. Hypotheses have
ranged from miraculous intervention to creative psychopathy. It has now been
suggested, based on Joan of Arcs own words and the contemporary descriptions of
scholars, that the source of her visions and convictions was in part ecstatic epileptic
auras. If this is true, then Joan of Arc joins the host of creative religious thinkers
suspected or known to have epilepsy, from St. Paul to Mohammed to Dostoevsky.

23.5. Head Injury (1830)
In 1830, the French Military Surgeon Jean-Pierre Gama reported an experiment
planned to unravel the mechanical events caused by head injury. His model was a
round glass flask with a long neck filled with a gelatinous substance that resembled
the consistency of the brain. Thumping the walls of the flask caused the movement
of thin wires embedded in the "brain-like" material, thought to represent the spread

                                        83
of forces within the brain. Gama thought that he could thus observe oscillatory and
vibratory movements of the wires representing the effects of concussion without
visible structural brain lesions. Although it was crudely constructed, entirely
subjective as to evaluation of results, and lacking the essential instrumentation that
only modern technology can provide, this hypothesis-driven pioneer experiment
should be regarded as the first to use the novel approach of physical modeling of
the brain. Even today, this approach has not been fully exploited.

23.6. The Knee Jerk (1875)
The knee jerk was first described by Erb and Westphal in 1875. In subsequent
years, neurologists used direct finger taps and light-weight chest percussion
hammers, but these proved to be inadequate for eliciting muscle stretch reflexes.
The first hammer specially designed for eliciting such reflexes was the triangular
reflex hammer introduced by John Madison Taylor in 1888. Over the next 25 years
several popular reflex hammers were designed, some of which are still in use.
These include the Babinski hammer with a round head fixed perpendicular to the
shaft, and Rabiner's modification where the head can also be attached parallel to
the shaft.

23.7. Nerve Transmission (1822)
The French physiologist Francois Magendie showed, in 1822, that the anterior roots
of the spinal nerves are motor and the posterior sensory. The English anatomist
Charles Bell claimed the discovery, but his claim was based on publications of his
papers in which the wording had been altered to be consistent with Magendie's
findings. Bell also appropriated Herbert Mayo's discoveries of the functions of the
fifth and seventh cranial nerves. Bell repeated his claims in a number of influential
publications, supported by his brothers-in-law John and Alexander Shaw. And for a
century and a half, Bell figured as the discoverer in most references to the subject.
During this period, several reviewers did go back to Bell's original papers, disclosing
Bell's falsifications in the republished texts. But Magendie was not definitely
acknowledged as the discoverer of the function of the spinal nerve roots until
Cranefield's (1974) treatise. Cranefield, and all other reviewers, overlooked
accounts from 1825 by P.W. Lund and F.D. Eschricht. They critically reviewed Bell's
early publications and reached conclusions similar to those of Cranefield concerning
the roles of Bell and Magendie in the discovery of the function of the spinal nerve
roots.

23.8. Neurone Doctrine (1866)
It was Wilhelm His who helped to lay the scientific foundation for the neuron
doctrine. The neurone doctrine is one of the central paradigms of the neurological
sciences and states that neurons are individual units. His' experimental approach,
which was based on the examination of embryological material, is of particular
interest because few investigators at that time were using it. By 1886, His had
compiled a collection of 12 human embryos of various measured lengths and
estimated gestational ages ranging from 2.15 mm to 24 mm, and 2 weeks to 8.5
weeks. He had studied the embryological development of nerve fibers in

                                        84
successively older specimens. For example, he contrasted the young embryo N,
whose nerves stopped only halfway with the distal part of the extremity completely
nerve-free, with the older embryo Zw, in which the nerves had already reached the
root of the fingers, but none were in the territory of the end phalanges. In the 1870s
and 1880s, using a discrete collection of 12 human embryos of consecutively older
ages, His observed the development of nerve fibers and, from this pattern of growth,
eventually suggested that nerve cells were individual units and that the transmission
of impulses was possible without direct continuity between neurons.

23.9. Seizure Treatments (18th Century)
Beginning in the late 18th century, facial flushing and bounding carotid artery pulses
during seizures were seen as evidence that seizures resulted from "venous
hyperaemia" of the central nervous system (CNS). Consequently, physicians used
digital compression of the carotid artery, and later carotid ligation, to abort seizures.
In the early 1880s, New York neurologist James Leonard Corning developed
several instruments for carotid artery compression in the treatment of seizures.
These devices included a two-pronged, fork-like instrument (the "carotid fork") for
temporary compression as an abortive treatment and an adjustable belt-like
instrument to encircle the neck (the "carotid truss") for chronic compression as a
prophylactic treatment. Corning's uncontrolled observations suggested that the
abortive treatment decreased the duration of seizures and that the prophylactic
treatment decreased the frequency of seizures. Corning later combined
instrumented carotid artery compression with other devices to decrease cerebral
blood flow, including transcutaneous electrical vagal nerve and cervical sympathetic
stimulation. Observed side effects of treatment included bradycardia (slowing of the
heart), dizziness, and syncope (fainting). Corning's use of instrumented carotid
compression and his precocious application of transcutaneous electrical vagal nerve
stimulation were not widely adopted by neurologists, and these techniques and
devices ultimately were abandoned in the late 19th century.

23.10.    Lluis Barraquer-Roviralta (1907)
Lluis Barraquer-Roviralta, a Spanish neurologist, described the syndrome of
progressive lipodystrophy, now known as Barraquer's syndrome, in 1907. The main
feature of Barraquer's syndrome is the progressive atrophy of the subcutaneous fat
of the face. Barraquer was also an expert in diseases of the peripheral nervous
system and developed medications to treat tabes dorsalis (locomotor ataxia), a
syphilitic infection of the nerves in which there is progressive degeneration of the
nerve fibers of the spinal cord. Although quite common in the past, the condition is
rarely seen anymore. Barraquer's drawings and photographs of the nervous system
were unparalleled and his iconographic collection helped to define the anatomy and
pathology of numerous neurological diseases. His pictures were featured in the
main neurology textbook of the time and are presently housed in the Museum of
Medical History in Spain. During his career at the University of Barcelona, Barraquer
was well known for his lecturing ability and for training the first neurologists in Spain.
In addition to describing progressive lipodystrophy, Barraquer also was the first to
describe the grasp reflex of the foot, now known as Barraquer's reflex.


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23.11.    Jean-Baptiste Bouillaud (1825)
In 1825, Jean-Baptiste Bouillaud read a paper at the Royal Academy of Medicine in
Paris supporting Franz Gall's theory of a relation between speech and the frontal
lobes. Bouillaud argued that if the frontal lobes are crucial to speech, two conditions
must be satisfied: when the frontal lobes are affected, speech must also be affected;
conversely, when the frontal lobes are spared, speech is also spared. Following
these principles, he tested and argued in support of Gall's theory by analyzing the
data from two neuropathological casebooks (Lallemand, 1820-1823; Rostan, 1820
and 1823). It is now known that Bouillaud was wrong, since the crucial dichotomy is
between the left and right hemispheres and not between the anterior and posterior
areas. What is interesting is that the actual data refute Bouillaud's conclusion.
Bouillaud experiments were replicated recently by reanalyzing the 147 clinical cases
described by Lallemand. There were, of course, some cases with frontal lesions and
speech disorders; other cases, however, had speech disorders with lesions outside
the frontal lobes, and still others had frontal lesions without speech disorders.
Although Bouillaud did not notice it, as expected, almost all patients with speech
disorders had a left hemisphere lesion.

23.12.    Dr. Jules Cotard (1840-1889)
Dr. Jules Cotard (1840-1889) was a Parisian neurologist who first described the
“delire des negations. Cotard's syndrome or Cotard's delusion comprises any one of
a series of delusions ranging from the fixed and unshakable belief that one has lost
organs, blood, or body parts, to believing that one has lost one's soul or is dead. In
its most profound form, the delusion takes the form of a professed belief that one
does not exist. Encountered primarily in psychoses such as schizophrenia and
bipolar disorder, Cotard's syndrome has also been described in organic lesions of
the nondominant temporoparietal cortex as well as in migraine. Cotard's delusion is
the only self-certifiable syndrome of delusional psychosis. Jules Cotard, a Parisian
neurologist and psychiatrist and former military surgeon, was one of the first to
induce cerebral atrophy by the experimental embolization of cerebral arteries in
animals and a pioneer in studies of the clinicopathologic correlates of cerebral
atrophy secondary to perinatal and postnatal pathologic changes. He was the first to
record that unilateral cerebral atrophy in infancy does not necessarily lead to
aphasia and was also the pioneer of studies of altered conscious states in diabetic
hyperglycemia.

23.13.    Samuel Collins - Comparative Neurology (1618-1710)
The concept of comparing the brains of various animals to individual human brains
was launched in the last half of the 17th century in England and was much
influenced by the formation of the European scientific societies and their attempts to
guide naturalist observations into a new systematics. An ambitious attempt to
document this trend in an extensively illustrated work of encyclopedic pretensions
was the singular publication of Samuel Collins (1618-1710), an energetic anatomist
and president of the Royal College of Physicians. His little known 2-volume folio
presentation, written in the vernacular for broad acceptance, contains the seeds of a


                                        86
science of comparative neurology with the largest collection of brain illustrations (as
well as of other organ systems) attempted in his era. Although lacking the
conceptual insight that might derive from a true "comparative" anatomy and an
understanding of the relations of different animals, the handsome engravings
exemplified the new direction of the 'enlightenment' of the scientific revolution and
are discussed in the context of relevant events of this period.

23.14.    Harvey Cushing - Pediatric Neurosurgeon (1869 - 1939)
Development of posterior fossa surgery remains Harvey Cushing's hallmark
contribution to pediatric neurosurgery. During the era before Cushing, posterior
fossa (brainstem glioma) lesions were considered inoperable, and only osseous
decompressive surgery was offered. The evolution of Cushing's surgical expertise
from subtemporal decompressions (removal of a piece of the cranium, usually in the
subtemporal region, with incision of the dura, to relieve intracranial pressure) to total
extirpation of vascular fourth ventricular tumors, combined with a dramatic decrease
in his operative mortality rate, reflects the maturation of modern neurosurgical
techniques. A comprehensive review of the medical records of Cushing's pediatric
patients treated between 1912 and 1932 revealed that procedures such as lateral
ventricular puncture (to decrease cerebellar herniation), transvermian approach to
midline tumors, and electrocoagulation were the key factors punctuating the path to
his pioneering achievements in posterior fossa surgery. The outcome of such
operations was improved by his recognition of the importance of tumor mural nodule
in cyst recurrence, as well as elucidation of the histogenesis of pediatric posterior
fossa tumors to tailor treatment including radiotherapy.

23.15.    Freud and Tourette's Syndrome (1890 – 1911)
A number of observers have taken Freud to task for failing to diagnose Frau Emmy
von N.'s (1888-9) involuntary tics and vocalizations and Daniel Paul Schreber's
(1911) coprolalia (cursing or filthy mouth) and convulsive tics as Tourette's
syndrome. None of Freud's critics, however, has placed Freud's understanding of
motor and vocal tics in historical context. None seems aware of the contests over
the classification of tic symptoms in the 1880's and 1890's, nor do they appreciate
the extent to which Charcot and Gilles de la Tourette had conceded that motor and
vocal tics, as well as coprolalia, could also appear as symptoms of hysteria. By
1893 (when Freud first wrote out his case of Frau Emmy von N.), both Gilles de la
Tourette and Charcot had defended themselves against Guinon's claim that
conculsive tics were always a symptom of hysteria by distinguishing those tic
symptoms that should be classified as "maladie des tics" from those that
accompanied hysteria. Yet Charcot and Gilles de la Tourette had agreed by 1890
that tic symptoms were possible outcomes of either maladie des tics or of hysteria.
What separated those afflicted with "hysteria", were particular inherited factors and
whether or not the patient could be cured of tics and vocalizations. Thus, within
Charcotian terms, Freud was hardly obligated to conclude that his ticcing and
cursing patients should have been diagnosed with maladie des tics de Gilles de la
Tourette.



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23.16.    Sir Victor Horsley (1857 – 1916) - A Pioneer in Neurosurgery
Immortalized in surgical history for the introduction of "antiseptic wax," Sir Victor
Horsley played a pivotal role in shaping the face of standard neurosurgical practice.
His contributions include the first laminectomy for spinal neoplasm, the first carotid
ligation for cerebral aneurysm, the curved skin flap, the transcranial approach to the
pituitary gland, intradural division of the trigeminal nerve root for trigeminal
neuralgia, and surface marking of the cerebral cortex. As a tireless scientist, Sir
Victor was a significant player in discovering the cure for myxedema, the eradication
of rabies from England, and the invention of the Horsley-Clarke stereotactic frame.
As a pathologist, Horsley performed research on bacteria and edema and founded
the Journal of Pathology. Horsley's kindness, humility, and generous spirit endeared
him to patients, colleagues, and students. Born to privilege, he was nonetheless
dedicated to improving the lot of the common man and directed his efforts toward
the suffrage of women, medical reform, and free health care for the working class.
Knighted in 1902 for his many contributions to medicine, Sir Victor met an untimely
death during World War I from heat stroke at the age of 59. An iconoclast of keen
intellect, unlimited energy, and consummate skill, his life and work justify his epitaph
as a "pioneer of neurological surgery."

23.17.    William Williams Keen –Neurosurgeon (1837-1932)
William Williams Keen was the catalyst for the advent of neurosurgery in the United
States. Keen served in the Civil War and collaborated with Silas Weir Mitchell in
studying injuries sustained to the nervous system. These studies culminated in the
publication in 1864 of "Gunshot Wounds and Other Injuries of the Nerves and Reflex
Paralysis," which first described causalgia (a burning pain often associated with skin
changes in the hand or foot, caused by peripheral nerve injury), reflex sympathetic
dystrophy (a neurological syndrome characterized by severe burning pain,
pathological changes in bone and skin, excessive sweating, tissue swelling and
extreme sensitivity to touch), and secondary paralysis. Keen’s most monumental
accomplishment undoubtedly was being the first surgeon in the United States to
successfully remove a primary brain tumor (1887) and have the patient survive for
more than 30 years. As the editor of "Surgery, Its Principles and Practice," Keen
invited Harvey Cushing to write the section on surgery of the head, which propelled
Cushing to international recognition and provided a foothold for the new specialty of
neurosurgery. Although Keen was a general surgeon, he had a special interest in
the nervous system. He treated patients with trigeminal neuralgia, performed cortical
excisions for patients with epilepsy, and devised the procedure of posterior upper
cervical root sections for spasmodic torticollis (movement disorder of the head). He
was the first surgeon to perform and advocate ventricular punctures. Keen served
as a consultant and surgeon to both Grover Cleveland and Franklin Delano
Roosevelt.

23.18.    Wilder Penfield - Sensory Map
The sensory map in humans was originally charted by the Canadian neurosurgeon
Wilder Penfield in the 1930s. Before operating on patients who suffered from


                                         88
epilepsy, Penfield stimulated different parts of their brains with electrodes to locate
the cells that set off their attacks. He could do this while the patients were awake,
since the brain does not feel what is happening to it. In this way, Penfield soon
learned exactly where each part of the body that was touched or moved was
represented in the brain. He then showed it in his famous "homunculus" cartoons of
the somatosensory and motor areas. The brain's map of the body extends along a
vertical strip of cerebral cortex near the center of the skull. The cortex-a large,
deeply wrinkled sheet of neurons, or nerve cells, on the surface of the brain's two
hemispheres-governs all our sensations, movements, and thoughts.

23.19.    Robert Remak (1815-1865) – Embryologist/Neurologist
Robert Remak was born in 1815 in Prussia (now Poland). He was a German
embryologist and neurologist who, in 1842, discovered and named the three germ
layers of the early embryo: the ectoderm, the mesoderm, and the endoderm. He
also discovered nonmedullated nerve fibers (1838) and the nerve cells in the heart
(1844) called Remak's ganglia, and he was a pioneer in the use of electrotherapy for
the treatment of nervous diseases. Remak studied under the eminent physiologist
Johannes M’ler at the University of Berlin and earned his M.D. degree (1838) with
an important dissertation on the fine structure of nerve tissue. Barred from teaching
by Prussian law, which closed that profession to Jews, he continued his research as
an unpaid assistant in M’ler's laboratory and supported himself by his medical
practice. In 1843 Remak petitioned directly to Friedrich Wilhelm IV for a teaching
position, but he was refused. That November he entered the laboratory of Johann
Lukas Schlein at the Charit Hospital, Berlin, where he continued his research on
nerve tissue and also began his investigations into the role of the germ layers in the
development of tissues and organs. In 1847, having by then acquired considerable
eminence, Remak finally obtained a lectureship at the University of Berlin. He was
promoted to assistant professor in 1859 in belated, though quite inadequate,
recognition of his extraordinary body of neurological and embryological research.

23.20.    Charles Scott Sherrington (1857-1952) - The Synapse
Sir Charles Scott Sherrington (1857-1952), a British physiologist, was awarded the
1932 Nobel Prize in physiology or medicine for his fundamental contributions to the
understanding of the functions of the central nervous system. While in 1897
Sherrington adopted the name synapse, the bridge between nerves, the concept of
the synapse emerged over a period of 2400 years. The early history was dominated
by Aristotle's concept of vital pneuma, which was thought to be derived from the
ether which fills all space. It is then taken in by the lungs, synthesized in the heart,
and then conducted via blood to the muscles. Vital pneuma then initiated the final
phase of the muscle's psyche, which was contraction leading to locomotion.
Aristotle's ideas had to be modified with the discovery by Galen and his students
(2nd and 3rd centuries C.E.) that nerves arising from the brain and spinal cord are
necessary for the initiation of muscle contraction. Aristotlean theory was modified so
that the vital pneuma delivered to the brain was converted to psychic pneuma,
which was then conducted along nerves to the muscles. About 1300 years later,
Descartes rejected the idea that organs and muscles possess a psyche. Rather, he


                                         89
emphasized that mechanical explanations must be sought when determining the
function of a muscle. He argued, in his corpuscular theory, that fine particles derived
from the blood, which he called animal spirits, were conducted and transmitted
along nerves to the muscle. Later, Galvani (b.1737) showed that animal spirits were
not corpuscular but electrical. In the 19th century, Matteucci, du Bois-Reymond and
Helmholtz, took Galvani's discoveries and showed that nerves possess a potential
across their walls that could give rise to a propagating transient potential change
which was transmitted to muscles with a finite velocity. It was, however, not until the
early part of the 20th century that a conceptual scheme for the synapse involving
transmitters and receptors was developed.

23.21.    Robert Bentley Todd - Father of Epilepsy (1809-1860)
Robert Bentley Todd (1809-1860) was a clinical scientist as well as Professor of
Physiology and Morbid Anatomy, with a special interest in the nervous system. At
Kings College, Todd met Michael Faraday (1791-1867), the greatest electrical
scientist of all time, at the nearby Royal Institution. On the basis of his own clinical
and experimental studies and his cutting-edge knowledge of neuroanatomy,
neurophysiology, neuropathology, and electrical science, Todd brilliantly developed
his concepts of the electrical basis of brain activity and of epilepsy, in particular.
Using a microscope, Todd perceived each nerve vesicle and its related fibers
(neuron in later terminology) as distinct entities for the generation of nervous polarity
(force). He also elucidated electrical transmission in the white nerve fibers
throughout the nervous system by unknown molecular mechanisms. In epilepsy,
Todd identified an increase in electrical tension, especially in the grey matter of the
hemispheres, leading to periodic, sudden explosive discharges, based on Faraday's
concept of disruptive discharges. Todd was the United Kingdom's first outstanding
neurologist and neuroscientist before these disciplines existed. Influenced by
Faraday, he proposed and confirmed the electrical basis of nervous discharges in
epilepsy more than 20 years ahead of Jackson, Ferrier, and Hitzig.




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      23.22.     Thomas Willis (1621-1675) - Founder of Modern Clinical
               Neuroscience
      Thomas Willis (1621-1675) is regarded as a founder of modern clinical
      neuroscience. He conceived the word "neurology" and left a body of work that
      defined mid-seventeenth-century medicine. Recent interpretations of Willis's work
      have led to a growing appreciation of his significant contributions to pediatric
      neurology, a specialty founded properly some three centuries after his death. Willis
      fused astute history taking and clinical observation (sometimes supported by
      subsequent post-mortem studies) into a structured medical intervention. Willis's
      practice was state of the art, being based on acceptance of Harvey, a traditional
      Galenic infrastructure, iatrochemistry and Gassendi's "psychology". Although Willis's
      discoveries became a cornerstone of modern medical science, his medical practice
      did not lead to any therapeutic advances. However, up to the mid-eighteenth
      century his works were internationally accepted for their practical usefulness. The
      corpus of material left by Willis affords a fascinating insight into the clinical rationale
      of a seventeenth century physician in his management of pediatric cases.

24.        ONCOLOGY

      24.1. Early Report of Cancer in a Child (1564-1617)
      Cancer in a young child is unusual and has always aroused curiosity. Proptosis and
      an enormous, rapidly growing unilateral tumor in a 3-year-old boy, prompted Pieter
      Pauw (1564-1617), a 16th-century anatomist, to perform an autopsy. His published
      notes from the autopsy were rediscovered in the 19th century, first by the German
      ophthalmologist and historian Julius Hirschberg and then by Edwin B. Dunphy, from
      Boston, who suggested that the child suffered from retinoblastoma, an interpretation
      that has held. Critical translation of the original Latin text suggests that an orbital
      tumor, such as embryonal rhabdomyosarcoma, would equally well explain Pauw's
      observations.

      24.2. Roswell Park, M.D. (1852-1914)
      Roswell Park, M.D., (1852-1914) is remembered for founding the world's first cancer
      institute a century ago, named The Roswell Park Cancer Institute. However, Dr.
      Park's accomplishments as a pioneer American neurosurgeon have been
      overlooked. After Park was appointed as Chair of Surgery at the University of
      Buffalo in 1884, he became the first American surgeon precisely to localize and
      remove a posttraumatic epileptic focus in the absence of external scars. Park
      introduced American physicians and surgeons to David Ferrier's research on
      localization of cerebral cortical function and Victor Horsley's techniques for
      extirpating epileptic foci. In 1895, Park became the first American surgeon to
      successfully treat spina bifida. In the same year, he wrote the first American
      monograph on surgery of the head. Park's case reports of successful operations on
      patients deemed almost incurable reveal boldness and ingenuity.

25.        ORTHOPEDICS



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      25.1. Osteogenesis Imperfecta (1844-1849)
      Osteogenesis imperfecta (OI) or Vrolik's syndrome is a heterogeneous group of
      inherited conditions arising from a variety of biochemical and morphological collagen
      defects. It was Willem Vrolik, Professor of Anatomy, Pathological Anatomy and
      Zoology at the Athenaeum Illustre (University of Amsterdam), who described in his
      Tabulae ad illustrandam embryogenes in hominis et mammalium, naturalem tam
      abnormem (1844-1849), a newborn infant with numerous fractures and
      hydrocephalus. In the Tabulae, Vrolik used in the heading of Plate 91 the term
      Osteogenesis imperfecta (in Dutch: gebrekkige beenwording). Vrolik also mentioned
      that the infant lived three days and that both the parents were suffering from lues
      universalis at the time of birth. On examination, the whole skeleton appeared poorly
      mineralized. The fairly large skull exhibited a broad and high forehead, large
      fontanels, frontal and temporal bossing, shallow orbits, and a protruding occiput.
      The calvaria consisted of many Wormian bones. The tubular bones, although of
      normal length and only slightly curved, were very thin, as were the ribs. All the
      skeletal structures showed one or more fractures and many fractures showed callus
      formation. Willem Vrolik was one of the first to realize that many skeletal dysplasias
      were not the result of a postnatal acquired disease, such as "rickets" or
      "osteomalacia" as many of his contemporaries believed. He thought that it might be
      due to insufficient intrinsic "generative energy." He substantiated this by stating that
      in this specimen, a primary impairment of ossification is present and not a
      secondary degeneration. The descriptions given by Willem Vrolik in some of the
      specimens generated the term Osteogenesis imperfecta, and the eponym Vrolik's
      syndrome, for this genetic disorder characterized by increased fragility.

26.        PATHOLOGY

      26.1. Forensic Entomology (13th Century to Present)
      Apart from an early case report from China (13th century) and later artistic
      contributions, the first observations on insects and other arthropods as forensic
      indicators were documented in Germany and France during mass exhumations in
      the late 1880s by Reinhard and Hofmann. After the French publication of Megnin's
      popular book on the applied aspects of forensic entomology, the concept quickly
      spread to Canada and the US. At the time, it was recognized that the lack of
      systematic observations of forensically important insects stood in the way of their
      use as indicators of postmortem interval. General advances in insect taxonomy, and
      ecology helped close this gap over the following decades. Many early case reports
      dealt with alleged child homicides, including the suspected use of sulphuric acid. In
      this context, it was shown that ants, cockroaches, and freshwater arthropods could
      produce postmortem artifacts suggestive of child abuse. After the World Wars, few
      forensic entomology cases entered the scientific literature. From the 1960s to the
      1980s, Leclecq and Nuorteva were primarily responsible for maintaining the method
      in Central Europe, with a focus on case work. Since then, basic research in the US,
      Russia and Canada has opened the way to the routine use of entomology in
      forensic investigations.



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26.2. "Jake Walk" - A Toxicological Tragedy (1930)
In 1930, thousands of cases of muscle pain, weakness of upper and lower
extremities, and minimal sensory impairment occurred in the United States. The
illness was caused by the consumption of an adulterated Jamaica ginger extract
("Jake"). Jake was an illicit beverage then popularly used in the Southern and
Midwestern United States to circumvent prohibition statutes. An additive, tri-ortho-
cresyl phosphate, caused severe, and only partially reversible damage to the spinal
cord and peripheral nervous tissue. Victims with resultant gait impairment,
sometimes permanent, were said to have the "Jake Leg" or "Jake Walk." Twelve
commercial phonographic recordings made between 1928 and 1934 by southern
rural artists, white and black, refer to Jake or Jake-induced infirmity. These reveal
preepidemic cultural familiarity with Jake, and the later, postepidemic performances
reflect a whimsical, even cynical, cultural attitude that those with "Jake Leg" were
suffering the wages of sin and should not be regarded as objects of pity or
sympathy.

26.3. Lead Exposure (Ancient to Modern Times
Lead concentration and isotope ratio data were determined from the tooth enamel of
77 individuals buried in England and spanning approximately 5,000 years from the
Neolithic era until the 16th century. Whereas other tissues may be affected by
diagenesis (physical and chemical changes) in the burial environment, the lead
concentration of tooth enamel is directly related to childhood exposure. This record
is preserved post-mortem and over archaeological time. Tooth enamel lead
concentrations in the prehistoric period appear to be variable within the range 0.04
to approximately 0.4 ppm (parts per million), with occasional higher levels. The
Romano-British and medieval periods show a marked increase in lead exposures
with enamel concentrations reaching up to approximately 40 ppm. These exposures
would today be associated with industrial pollution. Exposures appear to be highly
variable compared with modern people, with many medieval individuals having very
low enamel lead concentrations comparable with prehistoric people. The data
suggest that the maximum concentrations associated with 'non-technological'
exposure at any period are approximately 0.5-1.0 ppm, similar to that reported for
modern people in England.

26.4. Lead Poisoning Killed the Crew of the Franklin Expedition? (1845)
In 1845, the Franklin expedition left London with 2 ships and 134 men on board in
an attempt to find the route through the Northwest Passage. The ships were built
with state-of-the-art technology for their day, but provisioned with supplies from the
lowest bidder. After taking on fresh provisions in the Whalefish Islands, off the coast
of Greenland, the entire crew was never heard from again. Graves found on remote
Beechey Island indicate that three able-bodied seamen died during the first winter.
A note written on a ship's log, later found in a cairn, indicate that the expedition's
leader, Sir John Franklin, died during the second winter entrapped on the ice, by
which time 24 men had also perished. The remaining crew failed in their attempt to
walk out of the Arctic by an overland route. In 1981 Owen Beattie, from the


                                        93
University of Alberta, exhumed the remains of the sailors from the three graves on
Beechey Island. Elevated lead levels were found in all three sailors. While lead
poisoning has been a leading theory of the cause of the crew's deaths, blamed on
the crudely tinned provisions the ships carried with them from England, chronic lead
exposure may only have weakened the crew, not necessarily killed them. One of
three exhumed sailors also had in his intestine the spores of an unspecified
Clostridium species. The theory is that Botulism, type E, which is endemic in the
Arctic, may have been responsible for the deaths.

26.5. Vegetable Poisons and Death (1812)
The following was excerpted from the first edition of the New England Journal of
Medicine (NEJM 1;January 1812):
Mr. Brodie, author of experiments on the influence of the brain on the heart, had
communicated some very interesting experiments and observations on the different
modes in which death is produced by certain vegetable poisons. The observations
are as follows:
1. Alcohol, the essential oil of almonds, the juice of arconite, the empyreumatic oil
   of tobacco, and the woorara (a poison with which the Indians of Guiana arm the
   points of their arrows.), act as poisons by destroying the functions of the brain.
   Universal death takes place because respiration is under the influence of the
   brain, and ceases when its functions are destroyed.
2. The infusion of tobacco, when injected into the intestine, and upas antiar, a latex
   extract of the tree Antisaris toxicaria, when applied to a wound, have the power
   of stopping the heart and making it insensible to the stimulus of blood.
3. There is reason to believe that the poisons in these experiments, when applied
   internally, produce their effects through the medium of the nerves without being
   absorbed into the circulation.
4. When the woorara is applied to a wound, it produces its effects on the brain by
   entering the circulation through the divided blood vessels.
5. When an animal is apparently dead from the influence of a poison which acts by
   destroying the functions of the brain, in some instances it may be made to
   recover if respiration is artificially produced and continued for a certain length of
   time.

26.6. Tobacco’s Harmful Effects In History (10444 - 1600s)
It is well-known that tobacco smoking causes cancer of lip, tongue, tonsil and other
parts of the mouth, lung cancer, chronic bronchitis, coronary artery diseases and
emphysema. Historically, during the early 1600s, contemporary rulers, emperor
Jahangir of India James I of England and Shah Abbas I of Persia noticed the
harmful effects of tobacco and tried to stop this practice. Khalil Pasha issued a
prohibitory decree against smoking tobacco and he announced that anybody caught
smoking would have his lips cut and eyes taken out. In 1044, Russia also passed
certain regulations against smoking. In India, in the late 1600s, Guru Govind Singh


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      prohibited tobacco smoking for the members of the Sikh community. He said "Wine
      is bad; Indian hemp (bhang) destroyth one generation; but tobacco destroyth all
      generations'.

      26.7. Rudolf Virchow (821 – 1902)
      In 1858, Rudolf Virchow, the professor of pathology in Berlin University, published
      the book "Cellular Pathology". In this compendium of his lectures, Virchow
      introduced the use of microscopy for the study of human diseases. To a major
      extent, Virchow was helpful to the disciplines of veterinary medicine and pathology.
      Virchow, a scholarly physician, respected veterinary research, supported
      governmental veterinary education, and provided a role model for the veterinarians
      who were drafting control legislation of contagious diseases in livestock.

      26.8. Russian Medicine (18th Century)
      Among the innovations introduced during the dynamic reign of Peter the Great, in
      his attempt to bring Russia in line with countries in Western Europe, was the
      foundation of the Moscow Hospital School in 1707. Peter the Great entrusted the
      direction of the school to the Dutch physician and surgeon, Nicolas Bidloo. Bidloo
      dedicated himself to his students and to the organization of the school. He was also
      an excellent teacher as well as an expert in anatomy. The large number of surgical
      instruments listed in a catalogue drawn up when the hospital was damaged by fire in
      1738 testify to the quantity and variety of surgical procedures carried out at the
      hospital. Equal importance was given in course work to both theory and medical
      practice, and surgery was considered on a par with medicine at a time when
      surgeons in most European countries were considered to be of less importance.
      The high standards of the Moscow Hospital School soon won it great renown and
      later medical schools in Russia were modeled after it.

27.        PSYCHIATRY

      27.1. Amnesia (1892)
      Pierre Janet, in his famous paper (1892) on anterograde amnesia, addressed the
      theme of the disintegration of the human personality. Janet showed that the
      weakened personality, such as after a traumatic event, may lose the power to
      assimilate memories of current events. For example, after a severe shock, not only
      could a retrograde amnesia (a blotting out from memory from some period before
      the accident) occur, but also a continued or anterograde amnesia (an inability to
      remember events occurring after the accident). Janet detailed the circumstances of
      a very interesting case of amnesia resulting from an attack of hysteria, brought on
      by the shock of bad news. The patient, 'Mrs. D.', had wholly lost all memory of
      events that occurred during the month and a half before her attack, and since that
      time she had only been able to remember for a few moments what was going on
      around her. Janet demonstrated that memories which appear not to be formed are
      in fact formed. He showed that they exist somewhere in the patient's mind with the
      full vividness of ordinary recollections, and that they may spontaneously crop up in
      dreams, or may be called out by hypnotic suggestion, or by other methods.


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27.2. Bipolar Disorders (100 C.E.)
Perhaps the first person who described mania and melancholia as two different
phenomenological states of one and the same disease, was the Greek physician of
the 1st century C.E., Aretaeus of Cappadocia. Emil Kraepelin, however, in 1899,
unified all types of affective disorders in “manic-depressive insanity. In spite of some
opposition, Kraepelin's unitary concept was adopted worldwide. In the 1960s,
however, the rebirth of bipolar disorders took place through the publications of Jules
Angst, Carlo Perris, and George Winokur, who independently showed that there
exist clinical, familial and course characteristics validating the distinction between
unipolar and bipolar disorders. In addition, they verified several of the corresponding
opinions of the Wernicke-Kleist-Leonhard school. The concept of unipolar and
bipolar disorders has further advanced in the last three decades. Landmark
developments include the renaissance of Kraepelin's mixed states and of
Kahlbaum's and Hecker's cyclothymia and related affective temperaments, the
concept of soft bipolar spectrum (Akiskal), and the distinction of schizoaffective
disorders into unipolar and bipolar forms.

27.3. Mental Illness (19th Century)
Prior to 1800, insane persons often lived on the streets or were incarcerated in
asylums, jails, or prisons. The 19th century witnessed progression in the
understanding of psychosis, and the hospital management of psychotic patients
began. While Kraepelin in Europe described the symptoms of what would later be
called schizophrenia, Meyer developed humanistic treatment for the illness in the
United States. The early 20th century treatments for schizophrenia included insulin
coma, metrazol shock, electro-convulsive therapy, and frontal leukotomy.
Neuroleptic medications were first used in the early 1950s. Deinstitutionalization,
beginning in the 1960s, resulted in medicated, stable schizophrenics being released
from state hospitals. However, lack of stable living arrangements, misuse of funds,
poor medical follow-up, and drug use resulted in deterioration of a large segment of
this outpatient schizophrenic population.

27.4. Rorschach Test (1884-1922)
Hermann Rorschach (1884-1922) was a Swiss Psychiatrist who is best known for
devising the inkblot test that bears his name. By 1918, Rorschach had started to
experiment with the interpretation of inkblots by showing 15 accidental inkblots to
patients and asking them, "What might this be?" Rorschach published the results of
his studies on 300 mental patients and 100 normal subjects in the monograph
Psychodiagnostik in 1921. By this time, the number of inkblots had been reduced to
ten carefully selected images. Although ignored at first, today this work is regarded
as one of the great classics of psychiatry and psychology. But Hermann Rorschach
himself never experienced its success. He had difficulties finding a publisher, and
died of complications from appendicitis before he could properly test and evaluate
his invention. The Rorschach test was especially popular as a diagnostic tool in the
1950s. It later fell out of favor, criticized for its susceptibility to subjective
interpretation on the part of the evaluator. More recently, new comprehensive


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      scoring systems have been developed, resulting in improvements in standardization
      and norms.

      27.5. Schizophrenia (1911)
      Eugen Bleuler, in 1911, renamed the group of mental disorders with poor prognosis,
      which Emil Kraepelin had called "dementia praecox," "group of schizophrenias."
      Bleuler was a passionate and very experienced clinician. He lived with his patients,
      taking care of them and writing down his observations. Methodologically he was an
      empiricist and an eclecticist with a wide reading knowledge. Bleuler saw the main
      symptoms of schizophrenia being manifested in an impaired association of ideas, in
      disordered affectivity, in marked ambivalence and autism. For him these so-called
      pathological phenomena actually seemed to be only exaggerations of normal
      psychic functions. As a result, he viewed only quantitative, not qualitative
      differences between schizophrenia and normal psychic processes. In etiology as
      well as in therapy, Bleuler took into account psychological and neurophysiological
      mechanisms, thus combining organicism and dynamic psychiatry and coming very
      close to modern concepts, e.g. the one of stress and vulnerability. Bleuler's main
      merit is the stressing on an idiographic understanding of the patient and a plausible
      and subtle explanation of schizophrenia which helped to reduce the alienation of the
      affected persons.

28.        SURGERY

      28.1. Brain Surgery (7,000 B.C.E. – 900 C.E._
      Brain surgery is perhaps the oldest of the practiced medical arts. There is ample
      evidence of brain surgery, dating back to the Neolithic (late Stone Age) period.
      Unearthed remains of successful brain operations, as well as surgical implements,
      have been found in France, circa 7,000 B.C.E. Apparently, the success rate was
      remarkable. Africa showed evidence of brain surgery as early as 3,000 B.C.E.,
      documented in papyrus writings found in Egypt. Pre-historic evidence of brain
      surgery was not limited to Europe. Pre-Incan civilization used brain surgery as an
      extensive practice as early as 2,000 B.C.E.. In Paracas, Peru, south of Lima,
      archeologic evidence indicates that brain surgery was used extensively for the
      treatment of mental illnesses, epilepsy, headaches, organic diseases, osteomylitis,
      as well as head injuries. Surgical tools were made of both bronze and man-shaped
      obsidian (a hard, sharp-edged volcanic rock). Ancient Rome in the first century C.E.
      had its brain surgeon star, Aulus Cornelius Celsus. Asia was home to many talented
      brain surgeons: Galenus of Pergamon, born in Turkey, and the physicians of
      Byzance such as Oribasius (4th century) and Paul of Aegina. An Islamic school of
      brain surgery also flourished from 800 to 1200 C.E.. Abu Bekr Muhammed el Razi
      (852 to 932), was perhaps the greatest of Islamic brain surgeons. A second Islamic
      brain surgeon, Abu l'Qluasim Khalaf, lived and practiced in Cordoba, Spain, and
      was one of the great influences on Western brain surgery.

      28.2. Cataract Surgery (5th century B.C.E.)



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The earliest written reference to cataract surgery is found in Sanskrit manuscripts
dating from the 5th century B.C.E. It is believed that these writings were by the
Hindu surgeon Susruta who practiced a type of cataract surgery known as couching
or reclination. In couching, cataractous lens are displaced away from the pupil to lie
in the vitreous cavity in the back of the eye. This displacement of the lens enables
the patient to see better. However, vision is still blurred because of the unavailability
of corrective lenses. As recently as the middle of this century, couching was still
practiced in Egypt, India, and Tibet. In the Western world, recent excavations in
Babylonia (Iraq), Greece, and Egypt have uncovered bronze instruments that would
have been appropriate for cataract surgery. The first written description of the
cataract and its treatment in the West appears in 29 C.E. in De Medicinae, the work
of the Latin encyclopedist Celsus. In it, Celsus describes in this work the practice of
needling, or discission, of cataracts, a technique in which the cataract is broken up
into smaller particles, thereby facilitating their absorption. Interestingly, Hippocrates
does not refer to cataract surgery in his writings. Galen, the pivotal medical figure of
antiquity whose theories went unchallenged for more than 1,500 years, erroneously
believed that the lens rather than the retina was the seat of vision, and that its
removal would cause blindness. History also records the use of bloodletting,
antiphlogistics (agents to counteract inflammation and fever), and mercury to
prevent or dissolve cataracts, all of which were unsuccessful.

28.3. Laparoscopic Surgery (1901 to Present)
Laparoscopic surgery was initially introduced at the beginning of this century by
Dimitri Ott, Georg Kelling and Hans Christian Jacobeus. Von Ott inspected the
abdominal cavity of a pregnant women in 1901 and afterwards Georg Kelling
performed a procedure, called "koelioscopie." In the same year Jacobeus published
his first report of what he called "Laparothorakoskopie." In the following years
several authors in Europe and in the United States performed laparoscopic
procedures for diagnostic purposes. It was only with the introduction of the rod-lens
optical system and of the cold light fiber-glass illumination that laparoscopy became
more popular especially in gynecology departments. At that time, laparoscopy in
general surgery was mainly performed for the diagnosis of liver disorders and
abdominal trauma. In the 1980's, Lukichev and Muhe performed laparoscopic
cholecystectomy in humans. These rudimentary techniques did not receive the
attention they probably deserved and increasing interest in laparoscopy among
general surgeons developed only after the French gynecologist Mouret performed,
in 1987, the first acknowledged laparoscopic cholecystectomy by means of four
trocars.




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29.        VACCINES

      29.1. First Global Vaccination Occurred in 1803
      When he realized that the Spanish colonies in the Americas were being devastated
      by epidemics of smallpox resulting in thousands of deaths, Charles IV, King of
      Spain, sent one of his court's physicians to apply the recently discovered vaccine.
      Francisco Xavier de Balmis and a team that included three assistants, two
      surgeons, and three nurses, sailed from Spain on November 30. 1803. They
      vaccinated more than 100,000 people from the Caribbean Islands and South,
      Central, and North America, reaching up to San Antonio, Texas, and then traveled
      to the Philippines, Macao, Canton, and Santa Elena Island, landing back in Cadiz on
      September 7, 1806. During his journey, Balmis instructed local physicians on how to
      prepare, preserve, and apply the vaccine, while collecting rare biologic specimens.
      On the 200th anniversary of their sailing, recognition was given to this group for
      conducting what was the first global vaccination campaign that reached Texas and
      California.

      29.2. Emil von Behring – (1854-1917) – Diptheria and Tetanus
      Emil von Behring, the founder of Behringwerke, developed the first effective serum
      against diphtheria and tetanus. As a result, in 1901, von Behring was awarded the
      first Nobel Prize in Medicine. The "Children’s Angel of Death," a 19th century
      analogy for diphtheria, claimed more than 50,000 victims each year, with one of
      every two children dying. For the first time, in 1893, it was possible to treat the
      illness with a therapy that was developed by von Behring. To continue the
      development of lifesaving medicines, Behring founded Behringwerke in Marburg,
      Germany in 1904. A decade later, in 1913, he produced a vaccine which provided
      lasting protection against the once deadly diphtheria. These major contributions to
      the global community earned Emil von Behring the honorary title ‘Children’s
      Saviour’. In December 1890, an article appeared in the Deutschen Medizinischen
      Wochenschrift (German Medical Weekly), entitled "On the Occurrence of Immunity
      to Diphtheria and Tetanus in Animals." The article was co-authored by Behring and
      his Japanese colleague, Shibasaburo Kitasato. The publication opened the door on
      the emerging science of immunology and elevated Emil von Behring to the status of
      an internationally renowned scientist.

      29.3. Small Pox

        29.3.1.    Canadian Experience (1798 – 1962)
      Edward Jenner's first treatise in 1798 described how he used cowpox material to
      provide immunity to the related smallpox virus. He sent this treatise and some
      cowpox material to his classmate John Clinch in Trinity, Newfoundland, who gave
      the first smallpox vaccinations in North America. Dissemination of the new
      technique, despite violent criticism, was rapid throughout Europe and the United
      States. Within a few years of its discovery, vaccination was instrumental in
      controlling smallpox epidemics among aboriginal people at remote trading posts of
      the Hudson's Bay Company. Arm-to-arm transfer at 8-day intervals was common


                                            99
      through most of the 19th century. Vaccination and quarantine eliminated endemic
      smallpox throughout Canada by 1946. The last case, in Toronto in 1962, came from
      Brazil.

         29.3.2.   Vaccination in 1830's - Maybe We Should Take Note
      During the late eighteenth and early nineteenth centuries the Hudson's Bay
      Company served as a de facto public health agency across western Canada.
      Among its biggest challenges was combating the smallpox epidemics that
      periodically threatened the Aboriginal people of the region. Initially, the Company's
      employees turned to quarantine over variolation (inoculation of a susceptible person
      with material from a vesicle of an infected person) in order to prevent the spread of
      the disease to Hudson Bay in the summer of 1782. Although well thought-out,
      ultimately this policy proved unsuccessful. Within thirty years the HBC had turned to
      the newly discovered vaccination, a strategy that was to prove far more effective in
      fighting the disease. By the late 1830s the Company was able to mount an effective
      vaccination campaign that covered much of western Canada.

         29.3.3.   Vaccination - How Long Does It Last?
      While historically, more than half of the US population has received the smallpox
      vaccine, it is unknown what fraction is still protected against infection and disease.
      Residual protection and age-dependent case-fatality ratios have therefore been
      widely neglected in the current bioterrorism debate. As a result, data collected in
      1902-1903 data from Liverpool, United Kingdom, and from reintroductions of the
      disease to Europe in 1950-1971, were analyzed to estimate to what degree
      vaccinated cases were protected against developing severe or fatal disease, as well
      as how quickly this protection waned over time. Protection against severe and fatal
      disease was lost at the rate of 1.41% per year, corresponding to a half-life of 49.2
      years (95% confidence interval: 42.0, 57.3), and protection against fatal disease
      alone declined 0.363% per year. Thus, even 70 years after primary vaccination,
      77.6% of cases are still protected (95% confidence interval: 66.6, 85.4). Protection
      against severe disease should therefore extend for many decades after a single
      vaccination, and protection against death from smallpox may even be lifelong for the
      majority of vaccinees. This protection should greatly reduce the number of severe
      and fatal cases of disease expected in a bioterrorist attack, but residual protection
      may also increase the risk that some previously vaccinated cases who develop mild
      disease may remain unrecognized longer, while moving around freely and
      disseminating the infection.

30.        WARS

      30.1. Iliad (8th Century B.C.E.)

         30.1.1.   Battlefield Exacerbated Dysentery
      The earliest account of disease in Greek literature appears in the opening episode
      of Homer's Iliad which was composed sometime in the 8th century B.C.E. The god
      Apollo sent a plague among the Greek army before Troy in punishment for


                                             100
Agamemnon's insulting the priest Chryses when he came to ransom his captured
daughter. According to Homer, at the onset of the plague, Apollo only shot his
arrows at mules and dogs in the camp and then later at the Greek soldiers
themselves (Iliad I.9ff). What Homer describes is a highly communicable disease
with acute fever, sudden in onset and rapidly fatal, such as easily might attack an
army. After the Greeks appeased Apollo with sacrifices and by the return of the girl,
they set about cleansing the camp by throwing "defilements" into the sea. This
suggests that part of the disease was a severe dysentery exacerbated by battlefield
conditions.

   30.1.2.   Wound Management
Of the two epic poems attributed to Homer, the Iliad and the Odyssey, the Iliad
contains the more information concerning the treatment of injuries. Within the text of
this poem, Homer mentions nearly 150 different wounds. Most of these wounds are
described with surprising anatomical accuracy. For instance, in the Iliad, Harpalion,
a prince allied with the Trojans, is struck from behind by an enemy arrow. Homer
explains that this was a fatal wound, for although the arrow entered near the right
buttock, it sliced through the body, missed the pelvic and pubic bones, and hit the
bladder. Wound after wound is described in a similar fashion. Spears and arrows
strike specific internal organs according to their point of entry and trajectory. Homer
also seems to have had an appreciation of which kinds of wounds were lethal.
Wounds to the arms and legs were painful but not deadly, while all of the 31
different head wounds were lethal. Beyond the description of wounds, Homer also
recorded the care given to an injured warrior. Generally speaking, medical care
focused on the comfort of the wounded man and not on treating the wound itself.
Among the warriors, however, there were a few who were considered to be
specialists in the art of healing through means of herbal remedies and bandaging.
One of these doctors was Machaon, the son of the legendary healer Asclepius.
When Machaon was wounded, he was treated with a cup of hot wine sprinkled with
grated goat cheese and barley.

30.2. US Civil War

   30.2.1.   Lack of Medical Care - Major Cause of Death
While the work of Koch and Pasteur was just starting when the Civil War began in
April 1861, American physicians had little knowledge of the cause and prevention of
disease and infection. The Army Medical Department, which was responsible for the
care of the sick and wounded in the North, was unprepared. The staff of 90 doctors
was experienced in dealing with the health problems of small military outposts, but
had no idea of how to deal with large-scale medical and logistical problems. Two
soldiers died of disease (dysentery, diarrhea, typhoid, and malaria) for every one
killed in battle. Soldiers from small rural areas suffered from childhood diseases
such as measles and mumps because they lacked immunity. To remedy this, the
government created the U.S. Sanitary Commission. The commission was directed
by Frederick Law Olmstead who emphasized the virtues of clean water, good food,
and fresh air. Despite the efforts of the Sanitary Commission, some 560,000


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      soldiers died from disease. The second major cause of death was battlefield
      injuries, totaling around 200,000. The overwhelming number of wounded created
      problems in removing them from the battlefield. As late as 1862 there was no
      ambulance corps. Doctors in the field hospitals also had no notion of antiseptic
      surgery, resulting in extremely high death rates from post-operative infections.

         30.2.2.    The Hospital Ship (1862)
      It has often been said that the Civil War hastened the development of modern
      medicine in the US, mainly, because conditions during the war were so unsanitary
      that disease, even when treated, became a very serious problem. Among the many
      medical innovations that occurred during the Civil War was the first U.S. Navy
      hospital ship, the St. Philip, which entered service in 1862. About 620,000 men,
      360,000 Northerners and 260,000 Southerners, died during the Civil War. That
      number exceeds the total number of fatalities in all other American wars. In about a
      third of those who died on either side, the causes were battle wounds and
      subsequent infections. Physicians, nurses and volunteers all tried to treat the
      wounded within 48 hours.

31.        WOMEN IN MEDICINE

      31.1. Agnodice – A Women Doctor in Ancient Greece
      Agnodice is a figure often mentioned in the histories of the medical profession, but
      her story is largely unfamiliar to Classicists. She is credited with achieving the role of
      physician, although it was forbidden to her by law. It is highly unlikely that she was a
      veritable historical figure in third century Athens. More likely, she belongs to the
      realm of myth and folk tale. Her story comes to us through Hyginus, a Latin author
      of the first century C.E.. Since Agnodice desired to learn medicine, she cut her hair,
      donned the clothes of a man and became a student of Herophilos. After she learned
      medicine, she heard a woman crying while in labor and went to her assistance. The
      woman, thinking she was a man, refused her help, but Agnodice lifted up her
      clothes and revealed herself to be a woman and was thus able to treat her patient.
      When the male doctors found that their services were not wanted by women, they
      began to accuse Agnodice, saying that she had seduced the women patients and
      then accused the women patients of feigning illness in order to get visits from
      Agnodice. When she was brought before the law court, the men began to condemn
      Agnodice. Agnodice once again lifted her tunic to show that she was indeed a
      woman. The male doctors began to accuse her all the more vehemently for breaking
      the law forbidding women to study medicine. At this point the wives of the leading
      men arrived saying “you men are not spouses but enemies since you are
      condemning her who discovered health for us.” Then the Athenians amended the
      law so that freeborn women could study medicine.

      31.2. Clara Barton - Florence Nightingale (1823-1912)
      Clara Barton was 39 years old before she became involved in Civil War
      humanitarian activities. Prior to that time, three factors shaped her life. The first
      factor, phrenology, gave her philosophical principles to live by, especially "Know


                                               102
Thyself." The second factor was her experience of gender discrimination on her first
two jobs which strengthened her for living in a male dominated Victorian era. The
third factor was her psychohygienic therapy for her long term nervous condition
which changed her approach to mental illness. With this background, Barton went
on to gain world-wide acclaim. During the Civil War, she was revered as the
American Florence Nightingale, although she was not a nurse. At age 55, Barton
first embarked on the lengthy struggle to found the American Red Cross. She was
president of the Red Cross for 23 years and rendered aid and comfort at a host of
national and international calamities. On April 12, 1912, she died at age 90.

31.3. Mary Ann Bickerdyke - Woman Healer in the Civil War (1817-1901)
Mary Ann Bickerdyke, nurse, herbalist, and humanitarian, stood out as a singular
figure during the American Civil War and afterward. She advocated nutrition and
herbal medicines at a time when "heroic," if futile, treatments were often the rule.
Her compassion toward ill soldiers was legendary and provided her with the
nickname "Mother." Nevertheless, she did not hesitate to stand up to the
bureaucratic and occasionally incompetent physician administrators who opposed
her. Working in an arena typically off limits for women, she exceeded the bounds
proscribed for her gender during the 19th century as a naturopathic physician,
humanitarian, and social reformer.

31.4. Dorcas Hager Padget - Medical Illustrator (1906-1973)
Dorcas Hager Padget, a pioneer in the fields of neurosurgical illustration and
neuroembryology. Padget trained as a medical illustrator in the Johns Hopkins
School of Medicine's Department of Art as Applied to Medicine under Max Brodel.
She began her career working for Walter Dandy as his medical artist, gaining
worldwide recognition for her neurosurgical illustrations. With Dandy's
encouragement, Hager Padget undertook her own scientific research, studying
neurodevelopment and aneurysm formation in the circle of Willis by using human
embryos from the world-renowned Carnegie Collection. She made lasting
contributions to the field of neuroembryology, publishing the first major work on
neurodevelopment of the cerebral arterial and venous systems. Following Dandy's
death in 1946, Hager Padget began a full-time career as a scientific researcher, first
at the Department of Embryology at the Carnegie Institution of Washington in
Baltimore and later at the University of Maryland School of Medicine. She continued
to make contributions to the field of congenital malformations of the brain and spine,
coining the term "neuroschisis" to describe a possible mechanism of neural tube
damage leading to the creation of a myelomeningocele.

31.5. Dorothy Reed - Hodgkin's Disease (1902)
In 1902, Dorothy Reed, at the age of 28, wrote her paper on Hodgkin's disease. Her
biography reveals the difficult lives of women entering the male-dominated field of
medicine and medical research. Her historic paper on Hodgkin's disease is
remarkable for its brilliant observations and concise scientific reasoning.
Nevertheless, she was told that as a woman she could not hope for a career as an
academic pathologist. Motivated by the loss of her firstborn, she began a study of

                                       103
infant mortality, an interest that lasted throughout her career. In 1937, her efforts
were rewarded when Madison, WI received recognition for having the lowest infant
mortality of any city in the United States. Reading Reed's paper on Hodgkin's
disease, it is clear that her observations go far beyond a description of a specific
cell. Her presentation of macroscopic and microscopic features is remarkable for the
distinction between "young" and "old" growths: Reed saw Hodgkin's disease as a
process, rather than the spreading of a cancer. She was the first to note that those
most commonly affected are boys or young adults, especially those whose general
health before the disease had been excellent. Reed was also the first to note anergy
(skin reaction) to tuberculin. Dorothy Reed defined Hodgkin's disease in relation to
tuberculosis, described its pathologic features, and offered comments on its
pathogenesis, epidemiology, and immunology that still deserve to be discussed.

31.6. Mary Grant Seacole - Jamaican Medicine Woman (19th Century)
Mary Grant Seacole was born in 1805, in Kingston, Jamaica, to a Jamaican
doctress (medicine woman) and a Scottish naval officer. Later Seacole, herself
became a doctress, nursing British soldiers during epidemics of cholera, dysentery,
and yellow fever in Jamaica, Cuba, and Panama. After refusals by both the British
government and Florence Nightingale to be allowed to practice in Scutari, she
financed her own way to the scene of the Crimean War to serve both the comfort
and medical needs of the wounded soldiers. At night, Seacole worked side by side
with Nightingale at Scutari as a volunteer nurse. Seacole's fame grew
proportionately after she was seen helping wounded soldiers on the battlefields
even while the battles were still raging. Seacole died on May 14, 1881, in London.
One hundred years later, many members of the London black community, a few
members of the Nurses Association of Jamaica and the Friends of Mary Seacole
marched to her grave, honoring her as one of the greatest women of all times. Mary
Grant Seacole rose above the barriers of racial prejudice and demonstrated the
determinism, compassion, and caring that have became the hallmark of nurse
practitioners.




                                       104
                                     INDEX


Abbas, Ali ibn, 61, 100                    Bronze Age, 23
Abstinence, 67                             Brunton, Lauder, 39
Agnodice, 108                              Bubonic Plague, 58, 69, 70
Alchemy, 10, 58                            Buck, Pearl, 24
Alcohol, 13, 67                            Byzantine, 12, 43, 84, 88
Ali ibn Abbas, 60                          Cacao, 10
Amnesia, 101                               Cachexia, 53
Amputation, 60                             Caesarean Section, 20
Anesthesia, 29, 41, 54, 65                 Calliandra anomala, 10
Anorexia, 50, 53                           Cancer, 12, 31, 35, 42, 55, 63, 97, 100, 110
Anthrax, 34, 68, 69, 74                    Carrasquilla, Juan, 77
Antibiotic, 34                             Castrati, 54
Appendicitis, 58, 102                      Cataract Surgery, 103
Aristotle, 16, 18, 49, 95                  Cataracts, 20
Artemisia, 21                              Celsius, 34, 35
Arterial Pulse, 29                         Celsus, Cornelius, 20, 61, 103
Arthritis, 34                              Chagas Disease, 71, 72
Ascaris, 51                                Charles Scott Sherrington, 95
Asclepius, 16, 107                         China, 12, 24, 33, 63, 71, 98
Ashipu, 23                                 Chiron, 17
Aspirin, 34                                Chocolate, 10
Asylums, 42, 48, 50, 63, 102               Cholera, 34, 59, 63, 72, 73, 74, 110
Aztec, 10, 76                              Chopin, Frederic, 56
Babesiosis, 79                             Circumcision, 81
Babinski, 86, 89                           Civil War, 31, 47, 59, 66, 94, 107, 108, 109
Badianus Codex, 10                         Club Foot, 14
Banting, 54                                Copper Age, 22
Barraquer's Syndrome, 91                   Corning, James Leonard, 90
Barrough, Philip, 55                       Cotard, Jules, 92
Barton, Clara, 109                         Crookes Tube, 65
Baumes, Jean Baptiste Thimotee, 45         Cropper, John, 46
Bayliss, 53                                Cushing, Harvey, 44, 92, 94
Bean, James Baxter, 31                     Cushing's Disease, 42
Beaumont, William, 55                      Cushing's syndrome, 55
Benivieni, Antonio, 55                     Cyrene, 21
Best, Charles, 54                          Cystic Fibrosis, 56
Bill, Joseph H., 61                        Dante, 24
Bipolar Disorders, 101                     de Senac, Jean-Baptiste, 29
Birth Control, 21, 24                      Deaf, 42, 52
Black Death, 70, 71, 74                    Debridement, 32, 36
Bowditch, Henry Ingersoll, 56              Delphi, 22
Boxing Boys, 22, 23                        Dentistry, 30
Bright, Richard, 35, 43, 85                Diabetes, 40, 54
Bright's Disease, 85                       Diabetes Mellitus, 40, 54

                                     105
Digitalis, 30                                          Greece, 20, 43, 62, 70, 104, 108
Diodorus Siculus, 13                                   Gynecology, 67, 104
Dioscorides, 17                                        Handwashing, 37
DNA, 23, 71, 72                                        Hantavirus, 74
Dorcas Hager Padget, 109                               Harrower, Henry R., 44
Dorothy Reed, 110                                      Harvard Medical School, 56
Duchenne Muscular Dystrophy, 42                        Harvey, William, 28, 29
Dwarfism, 41                                           Head Lice, 75
Ear, 42                                                Healer, 24, 64, 107
Eclampsia, 43                                          Heart, 10, 17, 27, 28, 29, 30, 44, 45, 49, 53,
Edward Jenner, 105                                        61, 72, 87, 91, 95, 99, 100
Ehrlich, Paul, 59, 79                                  Heart Disease, 27, 30, 44, 45, 72
Emil von Behring, 105                                  Heliopolis, 13
Emmerich, Rudolf, 34                                   Hemophilia, 52
English Sweating Disease, 74                           Hemorrhagic Fever, 76
Ephemera, 63                                           Herbs, 10, 16, 33, 43, 64, 82
Epilepsy, 10, 21, 25, 51, 87, 88, 89, 94, 96,          Hering, Constantin, 39
  103                                                  Hermes, 21
Erasistratus, 17, 18                                   Hermione, 12
Ethics, 63                                             Herodotus, 13, 14, 88
Etruscan, 20, 21, 30                                   Herophilos, 49
Eye Disease, 20                                        Herophilus, 17, 18
Fat, 39, 44, 50, 91                                    Herz, Marcus, 64
Fever, 10, 11, 29, 37, 62, 63, 70, 73, 75, 78,         Hippocrates, 15, 18, 19, 34, 41, 61, 79, 82,
  80, 104, 107, 110                                       83, 84, 104
Fistula, 55                                            Hippocratic Oath, 63, 64
Fleas, 71, 77, 78                                      His, Wilhelm, 90
Fleming, Alexander, 39, 50                             Hodgkin's Disease, 110
Flexner, Abraham, 65                                   Holmes, Oliver Wendell, 56
Florentine Codex, 10                                   Hooke, Robert, 26, 27
Florey, Howard Walter, 39, 50                          Hospital, 31, 37, 40, 48, 50, 51, 64, 66, 67,
Fluoroscope, 40                                           73, 82, 83, 101, 102, 108
Fluoroscopy, 65                                        Hospital Ship, 108
Forensic Entomology, 98                                Humors, 10
Fourth Disease, 75                                     Ibn-i Nafis, 60
Franklin, Ben, 66                                      Iliad, 61, 106, 107
Galen, 17, 18, 37, 50, 60, 61, 82, 84, 95, 104         Imhotep, 14
Gallaudet, Thomas Hopkins, 42                          India, 12, 31, 33, 63, 100, 103
Gastric Juice, 55, 60                                  Influenza, 73, 74, 75
George III, 52                                         Jake Walk, 98
Germ Theory, 59                                        Jaundice, 45, 76
Gershwin, George, 24                                   Jefferson, Thomas, 66
Gladiator, 21                                          Jones, Henry Bence, 35
Glass Harmonica, 11                                    Kabbalah, 58
Golgi, Camillo, 26                                     Kedfinger, 64
Gout, 11, 58                                           Keen, William Williams, 94


                                                 106
Kidney Disease, 84                    Newton, Isaac, 10, 35
Kidney Stones, 11                     Nicholas II, 52
Koch, 57, 59, 68, 79, 107             Nightshade, 12
Laparoscopic Surgery, 104             Nitroglycerine, 39
Laxative, 14                          Noma, 31
Lead, 98                              Nostradamus, 58
Lead Poisoning, 99                    Nurses, 64, 67, 105, 108
Leeches, 11                           Odyssey, 107
Leprosy, 77, 81                       Ophthalmology, 20
Licorice, 12                          Opium, 21, 22, 38, 82
Lincoln, Abraham, 57, 65              Osteogenesis Imperfecta, 97
Lister, Joseph, 57                    Padua, 41, 56, 60, 82
Louis XIV, 51                         Padua University, 41
Lyme Disease, 78                      Papanicolaou, 35
Macular Edema, 45, 46                 Parkinson, James, 58
Magendie, Francois, 90                Parkinson's Disease, 58
Maimonides, Moses, 64                 Pasteur, Louis, 34, 46, 50, 57, 58, 59, 68, 74,
Malaria, 46, 72, 73, 80, 107             107
Manuscripts, 83                       Pathology, 14, 15, 18, 26, 47, 56, 58, 81, 91,
Mary Ann Bickerdyke, 109                 100
Matas, Rudolph, 29                    Paulus, 61
Maya, 10                              Pellagra, 47, 48
Measles, 75                           Penfield, Wilder, 94
Medical Dducation, 56                 Penicillin, 31, 39, 50
Medical Education, 65, 66, 82         Pennyroyal, 21, 22
Medicinal Plants, 13                  Per Ankh, 13
Meige, Henri, 62                      Periodontal Disease, 32, 81
Memphis, 13                           Pharmacology, 16, 17, 18, 39, 44
Mental Illness, 102                   Pierre Janet, 101
Mercury, 27, 104                      Pitt, William, 52
Mering, 38, 54                        Plato, 16, 19, 20
Merman, Ethel, 24                     Plenck, Joseph, 33
Merrick, Joseph, 48                   Pliny, 13
Mesopotamia, 23, 81                   Poison, 12, 30, 100
Metchnikoff, Elie, 46, 59             Polio, 14
Midwife, 66, 67, 81                   Porphyria, 52
Minkowski, 54                         Prout, William, 35, 59
Mobitz, Woldemar, 29                  Psychosomatic, 12
Morphine, 13, 38                      Puerperal Fever, 50
Movement Disorders, 62                Queen Victoria, 52
Mummy, 14, 15, 22                     Rees, George Owen, 35
Myasthenia Gravis, 47                 Remak, Robert, 95
Myrrh, 13, 21, 32                     Robert Bentley Todd, 96
Nerve Transmission, 89                Roentgen, 40, 65
Neurofibromatosis, 48                 Roman, 17, 18, 20, 21, 31, 33, 61, 62, 64,
Neurone Doctrine, 90                     68, 69, 81


                                107
Rome, 18, 19, 20, 54, 62, 70, 81, 103         Stomatitis, 31
Roosevelt, Franklin D., 53                    Strabo, 13
Rorschach Test, 102                           Surgery, 19, 22, 28, 29, 32, 40, 41, 42, 50,
Roswell Park, 97                                54, 55, 57, 61, 65, 82, 83, 84, 87, 92, 93,
Rudolf Virchow, 100                             94, 97, 101, 103, 104, 108
Russian Medicine, 100                         Synapse, 95, 96
Sabuncuoglu, Serefeddin, 84                   Tetralogy of Fallot, 27
Saint Vitus' Dance, 62                        Texas Fever, 78
Samuel Collins, 92                            Thomas Willis, 96
Scarlet Fever, 78                             Thoracotomy, 61
Schistosoma haematobium, 15                   Thyroidectomy, 54, 55
Schistosomiasis, 15                           Tobacco, 100
Schizophrenia, 92, 102, 103                   Toothpaste, 32, 33
Scurvy, 49, 50                                Toothworm, 32, 33
Seacole, Mary Grant, 110                      Tourette's Syndrome, 93
Seizure Treatments, 90                        Trichinella, 51
Semmelweis, 37, 50                            Tuberculosis, 11, 15, 38, 40, 56, 59, 74, 79,
Semmelweis, Ignaz Philipp, 37                   110
Seneb, 41                                     Typhoid Fever, 80
Senhouse Kirkes, William, 28                  Ulcer, 51
Silphium, 21                                  Vaccines, 105
Sims, James Marion, 67, 68                    van Gogh, Vincent, 25
Sitophobia, 50                                van Leeuwenhoek, Anton, 26, 27
Sleep Apnea, 25                               Vegetable Poisons, 99
Small Pox, 105                                Vertigo, 43, 51
Smith, Homer, 85                              Vesalius, Andreas, 56, 60
Snow, John, 73                                Victor Horsley, 93
Soranus, 66                                   Waksman, Selman, 50
Sozodont Tooth Powder, 13                     Wars, 106
Spain, 10, 80, 84, 91, 103, 105               Washington, George, 52
Spanish Flu, 74                               Women in Medicine, 108
Starling, 53                                  Wound Management, 107
Stevenson, Robert Louis, 25                   X-rays, 40, 65
Stokes, William, 27                           Yellow Fever, 80




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