What'sNew In EducatIOn,Research
and Community Service Or Pe ter Temple -Sm ith (centr e) and mlc ro- .
su rgeon Mr Graeme Southwic k (rig h t) att emp t to
co rrec t male toterttt tv by mic ro-surgery . The
2-81 tech nique enable s the m to by-pass a blockage
in the epid idymis by joining the vas de fere ns
(diagram rig ht) directly to th e minute ep idi dym is
duct . The at tending nurse is Sis ter Ronnie Ho b
lSSN 0159-950 day.
Phot o: Terry Martin. Diagram : Mrs Sue Sim pson .
~""=:--- ~f~~5 ':; :I~nl ~~o
New hope on male
ce t e r e ns
vas defe rens store sperm prior to ejaculation .
Dur ing their passage dow n the epididymis
the sperm undergo a maturation process.
MONASH rellearchers are developing becoming active and fert ile.
mlcro-surglcel and diagnostic techniques Dr Peter Temple-Smith. of the Monash down the epididymis and his sperm were ac
wh ich could lead to Improved treatment of anatomy department. and micro-su rgeon. Mr t ively motile and appear structuralty mature.
llome typell of Infertility In men. Gra8me Southwick, using rabbits , have Because of the low level of the jo in there is a
It is estimated that one in 10 couples have developed a micro -surg ical technique Which good chance that the sperm will be fertile .
an infertili ty problem . In about 40 per cent of enables them to by-pass the blockage in the The continued post -operative absence of
cases the infert ility is due to the ma le. One epididym is by joining the vas deferens direct sperm in the other men does not neceasarily
man in 26 is infert ile, and, from research at ly to the minute epididymis duct. mean that their operat ions were unsucces
Mona sh, it seems that one in 35 or 40 is ac Using single duct microsurgery they have sful. Some past clin ical observations Indicate
tually sterile. achieved a 90 per cent success rate in that sperm may not appear in the ejaculete
The Monash research, wh ich Is being done rabbits. All 90 per cent had healthy young. unt il 12- 1B month s afte r the anastomosis
in conjunction w ith the Infertility Clinic at In conjunction w ith Professor David de has been made, especially if the vas has bean
Prince Henry's Hospital, is concerned ma inly Kretser. they are now beginn ing to use th is joi ned to the head of the epididymis.
w ith a type of male infertility in wh ich sperm techn ique in men who have an obstruction The Mo nash team hope that the ir research
are produced in the testes , but are unab le to with in the epididymis and are infertile. using the rabbit w ill shed some light on this
pass into the vas deferens, the sperm's exit De Kretser says the by-pass operation, aspect of the operetion.
route , beceuse of a blockage In the called an anastomosis, has been done before " Obviously, if t he join la made at higher
epididym is. as a normal surgica l procedu re, but with a levels, the prognosis is not as good, " de
The epididym is lies behind t he testes and success rate of less than five per cent. Kretser says, " since sperm need to pass
consists of a coiled system of 10- 15 t iny Results were poor, he says. because the down the tract to mature and it Is more
ducts wh ich lead to 8 single convoluted duct vas deferens was joined to the whole difficult to join tha vas deferens to the smaller
wh ich, in turn , leads into the vas deferens. epididym is, not J t to a single duct.
UB diameter ducts. "
The epididym is and the first portion of the Southwick and Temple-Smith 's micro The diagnostic method whi ch enables the
surg ical techn ique has now been teated at Monash team to ident ify patients unsuitable
The Avenue Hospi tal on about one dozen for the obstru ct ion-reversal operat ion arose
M'ONASH REVl'EW'is produced four times men from the Infertility Clinic at Prince from the discovery that some men have nor
yearly by the Information Offrca, Monash Henry's Hosp ital. mal sperm counts but their sperm are "quite
University. Wellington Road. Clayton, vsc So far only one of t hese men has produ ced inact ive" . The same men suffer from a
toria. 3 16 8 . Inquiries should be addressed to
the Editor. c/o the Information Office. a heaIthy sperm count after the operat ion. In respiratory disease called bronch iectasis .
t his case the loin was made about half way
Regisle red 1 pos llng as
a pcnoorcat. Cateqory B Co ntinu ed overlea f
MONASH REVIEW JUNE
MONASH art historian Memory Hol
loway has been commissioned by the
National Gallery of Victoria to produce a
book on Its small but fine collection of
Picasso etchings. which are rarely seen by
The book, which is expected to be
publ ished later th is year , w ill bring the 22
etchings and other engravings together for
permanent display .
The prints, stored in the Prints and
Drawings Room at the National Gallery , can Monash art hist orian Memory Holloway (ce ntre)
conduct s a tutorial on Picas so at th e National
only be shown occasionally because of the ir Galle ry. She has be en com missione d by the
frag ility. They are very sensit ive to light and re-valuation of Picasso , who is regardad by Gallery to produc e a book on its tin e but rarely
m any art ists and art histo rians as the art ist of se en Pica sso etc hin g s. Some of the etchin gs
could be ser iously damaged if put o n are pictured abo ve.
permanent display. the century because of his innovation, artistic Phot o: Ric k Crompton.
Holloway says the book wi ll enab le many techn ique and infl uence on modern art.
peop le, who might not otherwise have the This renewed interest in Picasso reached
opportunity , to enjoy the etch ings , wh ich it s peak in 1979 with a huge exhibition in
represent the finest Picasso collect ion in Paris of the art ist's works, donated by his
fam ily to the Frenc h nat ion in lieu of death Holl ow ay saw both exh ibit ions . The suc
Australia. The only other major Picasso
duties. cess of the exhibit ions and the renewed
wo rks in Austra lian galleries are a painting in
SUbsequen tly the works were sent to New interest in Picasso wh ich they generated,
the Queensland National Gallery and a
York for a large Picasso retrospective before gave her the idea of producing a permanent
recent ly acqu ired paint ing in the NSW gal
being returned for perm anent hous ing in a record , in book form , of the V ictor ian
Paris museum. colle ct ion .
Publication of the book is part of a general
The earliest etching in the National Gallery
of Victoria's Picasso collect io n is dated 1904.
The last one was done in 1973.
Malei n f ertiiit Y Conti nued from Page 1 The 1904 etching, called " The Frugal
Meal", depicts a poverty-stricken man and
woman sitting in a cafe.
Holloway says the etch ing was done
" If you examine the teils of the sperm of team plans to examine cil ia from the nasal Picasso dur ing his Blue Period, when , dogg e"
these men end the cilia from their resp iratory epithelium of the patient to see If It is abnor by poverty and failure, he began to paint in
surfaces under the microscope, you w ill find mal. melancholic, predominantly blue tones.
the same abnormality:' de Kretser says. " If the nasal cilia lack dyne in arms, " de The subject matter of the 1904 etching
"A sperm tail has nine doublet tubules Kretser says, " cilia in the epididymis w ill underl ines Picasso 's compassion for society's
which run the ent ire length of the tall ." he probably lack them also and w ilt be unable to outcasts, a concern wh ich was to appea r
says. "I n cross -sect ion , they look like the d ial propel the sperm down the tube . time and again in his art .
of a telephone. "ln that case, there is no point in Ten of the Nat ional Gallery's etc hings, she
" In normal sperm there are tiny arms, attempting to reverse the obstruction. The says, are from t he famous Vollard Sui te, a
called dyne in arms , which extend from each sperm would remain im mot ile even if the collection of 100 engravings and etch ings
of these m icro -tubule pairs . W ithout these obstruction were reversed. " w hich Picasso did over a 1O-year per iod fro m
arms the sperm cannot become motile. As well as cond uct ing further research on 1937 for publ isher and art dea ler Ambroise
" These arms are missing from the sperm human subjects, the Monash team Is Volla rd.
of men In whom the sperm are inactive. They continuing its research on rabb its because of " The etch ings were executed in exchange
are missing also from the respiratory ci lia , the ir fecundity and the sim ilar ity of the ir for some paintings that Picasso wanted: ' she
which also serve a locomotive function , reproductive systems to humans. says.
sweep ing mucus and debr is out of the In these exper iments, the vas deferens will " They are very evocative and sensual
resp iratory passages." be jo ined et various locations in the body and pieces. done with utter ease. I th ink th is is
Some men who have an obstruction in the head of the animal's epididymis in an attempt largely related to the fact thet by th is time
epididymis also suffe r from bronchiectasis. to perfect the techn ique and to determine the Picasso had left his ballerina w ife Olga , who
The Monash team is working on the distance down the tube that the sperm has to wa s socially very ambitious, and had met a
hypothesis that In these cases the travel to become mature. Present indications woman called Marte-Therese Walter.
obstruction Is a "plug" of sperm which is are that it is not very far. " He seems to have been very happy with
unable to move because the cilia that nor The research is being funded by the Marie-Therese. It was a very relaxed and
mally propel it down the epididym is leck National Health and Medical Research Coun peaceful time for Picasso . His happiness ap-
dynein arms and are therefore immotite. cil. Monash University and the World Health
Before carrying out further operations, the Organ isation. Contin ued on Page 3
MONASH REVIEW 2 JUNE
MONASH researchers at the Queen
Victoria Medical Centre are developing
techniques for the freezing and
preservation of human embryos,
The work, which has been approved by the
hospital 's ethics committee, is aimed at
improving the success rate in the Monash-led
in vitro fert ilisation program . .:..:tE~lIIl1t ;~ . . . . - -,
The Mona sh team , led by Professor Carl The wo rld 's first in vi tro twins. A m anda (le ft) an d Step hen Mays.
Photo: Chr is Barham. Copyright: Daily Mail, London. ANG Ltd.
Wood, has already announ ced the birth of
the world's first in vitro twins, Amanda and bleeding . Uterine bleeding occurs in about 15 and then plunged into liqu id nitrogen. Its
sphen Mays, who were born at the Queen per cent of patients, he says, and is not temperature then is minus 196 degrees C. At
icto ria Medical Centre early this month . pecul iar to mothers undergoing the In vitro that temperature all metabolic processes
Stephen underwent surgery for a heart
procedure . It is " feirly common" in normal stop and the embryo can be kept frozen In
defect. Six babies have now been born in the
program as a result of fertilisation of the pregnancy. defin itely . as far as is known .
moth er's egg outside the womb. and a birth The embryo will not implant in the womb " The only thing we 've been concerned
is expected. on average, each month until the if there is bleeding. he says. So embryo about is the effect of background radiation
end of the year. transfer has to be delayed to a suitable cycle . which might damage the cells ," Trounson
The work on embryo freezing is being The alternative to freezing the embryo for says. " But research by Dr David Whit·
done by Dr Alan Trounson, a lecturer in the later transfer is to collect another egg by tlngham on mouse embryos suggests that
Monash department of obstetrics and laparoscopv . which would mean an extra this is no problem. "
gynaecology, and Mrs Linda Mohr. a operation for the mother. with no guarantee To thaw the embryo, the procedure is
research assistant. . that conditions would be right the next time. reversed.
With the consent of the parents, they have Another situation in which problems can Trounson says a number of normal,
successfully frozen a dozen embryos , all of arise is when the mother becomes ill. healthy progeny have been born to mice and
which appeared to be normal on thawing. Another factor which complicates the cattle , as a result of implantation of frozen
Two of the embryos were transferred back problem is the use of the ertificial hormones. embryos. But, in cows. the embryos do not
into the mother's womb, but no pregnan cy clomiphene and human chorionic seem to be viable unless they are frozen at
resulted . gonadotrophin (HCGJ to induce ovulation. A the blestocyst stage. By then the growing
Trounson says the freezing techn iques are side effect is that invariably two or more eggs embryo is a bell of 120-150 cells
being developed to give the team "a little are produced . surround ing a central fluid-filled cavity.
more elasticity in its work on In vitro fer Tha fact that there are two or more ripe If a healthy human embryo could be
tilisation " . eggs increases the chances of growing an grown in a nutritive madium to that stage,
A number of situations can arise in which ambryo . but it also creates an ethical then frozen, and later transferred back to the
"5 desirable to delay transfer of the embryo problem . What do you do with the excess womb. there would be no problem in
ck into the mother's womb until the next embryos? If the embryos are not transferred achieving pregnancies from frozen embryos,
cycle, he says. beck into the womb or used for further Trounson says.
One situation is where there is uterine research, they have to be discarded . But viable human blastocysts cannot yet
" A fter lengthy discussions, " Trounson be grown outside the womb, he says. The
Picasso says, " t he hospital's research and ethics
committee recommended that. provided
parents give their informed consent, normal
embryo has to be transferred at the eight-cell
stage, or, at the earliest. the four-cell stage.
The human embryos et the Queen Victoria
Co nnn ued Ir o m Pag e 2
excess embryos should be preserved by Medical Centre are being frozen at the four
pears to be reflected in his work in this period freezing for possible re-implentation in the and eight-cell stage.
which was prolific and very creative. " future rather than being discarded . " W e believe that humen embryos will
Holloway says there are also several The technique which Trounson is using to prove easy to freeze." Trounson says. " They
lithog raphs and a very fine drawing in the preserve ambryos at the Queen Victoria look as though they survive well. In terms of
Victorian collection. The drawing belongs to Medical Centre is one wh ich he and Or damage, our frozen human embryos look
Picasso's Cubist period , when he and the Willadsen Steen developed et Cambridge more like mouse embryos than cow embryos .
French painter Georges Braque attempted to University in 1976 while conducting research " The problem is we haven't done enough
look at an object from many different angles on the freezing of cattle embryos. yet to work out the optimum method of
and build up a 3-dimensional image in paint The embryo is first "passaged" through freezing. and we will have to transfer at least
by reducing forms to simple planes, using a three or four solutions containing. in 15 healthy thawed-out embryos to the womb
very small color range - virtually black and increasing concentration. a chemical called a before we can expect a pregnancy .
wh ite. cryo -protectant. This chemical. either "After all, we used more than 300
Some of Picasso's work is difficult to glycerol or dimethy sulphox ide, enables the embryos to get the procedure working for
understand, she says. But what he is often embryo cells to survive freezing . cattle. and other researchers used thousands
trying to do is to dissect a figure into its The solut ion containing the embryo is of embryos to get it working for mice."
various parts and to present perception of en cooled from room temperature to minus six Trounson presented the results of his
object in its totelity - not only what we see degrees C at which stage ice crystals start to research to the recent 3rd World Congress on
at a particular moment. but also what we form . It is then slowly cooled in a Human Reproduction In Berlin. Where he was
don't see but know is there . programmable freezer to minus 80 degrees C one of three major lecturers.
MONASH REVIEW 3 JUNE
way of life
TWO boy scouts Investigating a cave at
Springfield Gorge. near LoncefleJd, last
year, discovered an old Aboriginal burial
Inside the cave was the dessicated body of
a young woman enclosed in a net bag.
Archaeologists believe the woman 's body
was placed in the cave about 300 years ago.
Working in conjunction with the Vlctorlen
Archaeological Survey and the National
Museum . Monash botan ist Dr Beth Gott
has now identified the fibres used to make
and tie up the bag. Three hundred years ago the body ot an
A painstaking examination of the largely aboriginal woman was pla ced in a bag in this
intect bag has shown that the flax used as a cave near t.en cettetd. Monash bot anist Beth
Gott (le ft) has identified the fibres used to mak e
tie was made from a plant called DlaneUa and tie up the bag . The blue flax lily (Inset) was
revolute (the blue flax lily) . The main part of used 8S 8 tie .
the bag appears to have been made from the
inner bark of tha wattle. Gott says it began to disappear with the
Gott works in the Monash botany introduction of sheep and cattle which ate
department on a grant from the Australian not only the leaves of the plant but also its
Inst itute of Aboriginal Studies. roots . which were very close to the surface .
From the plant ramains at an "Who can blame the Aborigines for raiding
archaeological site in the Western District. farmers ' fields for potatoes?" she asks.
she has also established that 19.000 years By the time the first Europeans arrived the
ago - at the height of the glacial period in Aborigines had lived in the Western District
southern Austral ia when Australia was linked for 40,000 years at least and had achieved a
to Tasmania by a land bridge and the climate balance between population and resources .
generally was bitterly cold and dry - there How did they manage this? It was not due
was a good fresh water stream in thet part of to starvation.
the Western District. at least. Gott says some clues are emerging from
The stream would have provided a good research in Africa , where it has been shown
food and water supply for the local from analysis of blood samples that fre
Aborigines. There is a tendency also. she says. to think quency of suckling appears to determine
Gott infers the existence of the streem that. because the Aborigines were a whether a woman conceives or not . W ith I
from deposits of seeds of the weter plant stoneage people , and didn't engage in almost continuous breastfeeding practised .. ,
Mvrlophyllum as well as seeds of a species farming. they had an inferior diet and hunter gatherers. it seems, a hormone is
of Pimelee, Plmlllllll plIuclflorll. which she lifestyle. produced which, in effect, prevents ovulation,
retrieved from the archaeological site. She believes the use of fire and the " Hunter gatherers suckle children
believed. on the basis of carbon dating. to be gathering practices of the Aborig inal women whenever the child requires it. not every four
about 19.000 years old. were a type of farm ing , improving the growth hours as European women do, but. perhaps .
This particular Pimelea. which is of food plants which they used. every 20 minutes:' Gatt says. " This elmost
associated with mountain streams , is not " The evidence from anthropological continuous suckling produces a hormone
found today in the Western District . It is studies shows that the hunter gatherers live which basically prevents ovulation,
found only in mountain areas of eastern Vic very well :' she says. " The Aborig ines, before " If the frequency of suckling is stretched
toria , the Europeans came. had plenty of animal to as much as four hours. the hormone Is ap
" It is remarkable that after being buried in protein. as well as roots , seeds and fru it as a parently not produced or is not produced
the mud for 19 ,000 years the Pimelea seeds food source. regularly ."
were quite recognisable: ' she says. " The Western District was full of swamps. This frequency of suckling. Gott believes.
It is only now , as evidence accumulates which are ecologi cally very productive. There could be one of the reasons for the
from archaeological sites, Gott says. that we were water birds . the eggs of water birds , Aborigines' success in balanc ing population
are beginning to understand the complex yabbles . eels, fish and fresh water mussels. and resources.
nature of the Abor igines' way of life. " W e tend to forget how many swamp s It could also hold the key to why the
"We tend to think of them as being part of there were in the Western Dist rict. So many Aborigines did not engage in agriculture as
the eco-system , but not affecting it very have been c o m p l e t e l y drained for we practise it .
much : ' she says. agriculture ," Go tt says there are a number of
" This is a very wrong impression. The One of the staple foods of the Aborigines anthropologists who believe that a people
Aborigines regularly used fire as a tool. They at the time of the arrival of the first only turn to agriculture when they are forced
used controlled burning to bring up fresh Europeans was murnong. a dandelion-like to do so by population pressures.
plants, open up the country, attract animals plant with a yellow flower, whi ch, Gott says. This was not necessary for the Aborigines
to an area for hunting. or drive them to other was then found allover the Western District. who had managed to keep population and
areas." It has now almost disappeared. resources in balance .
MON A ~H REVIEW 4 JUNE
Analysis of pollen samples taken by Dr A. Pete r
Kershaw (tneet) from this crater lake on the
Atherton Tableland shows a dramatic change in
the Australian landscape over the past 120,000
years . The predominance 01 eucalypts today
may be due partly to the use of fire by the
today in areas drier than those occupied by
tropical rainforest. but Is only found in
sma ll patches i n north -eastern
• From 38.000 to 10.000 years ago there
was a dramatic change . Araucarla dry
forest was replaced by Iclerophylt
wood land. The emergence of the eucalypts
as the dominant vegetation coinc ided with
a decrease in rainfa ll and a sharp increase
in charcoa l particles.
• From 10.000 years ago almost to the
present. much of tha Atherton Tableland
was re-occupied by trop ical rainforest un
der increased rainfall levels.
Recent changes In vegetation - caused
by the activ ities of European settlement
are indicated in the topmost sedlmant
samples by the presence of pollen derived
from introduced waed species. Thera Is also
Aborigines may have increased charcoal.
The decline of Araucarla forest 38 .000
yaars ago was associated with a decrease in
changed our landscape rainfall . but from evidence of sea-level
changes. Kershaw says. it is likely that similar
dry periods occurred prior to that.
The question arises: Why did Araucarla
forest. which must have covered extensive
ABORIGINAL man may have been and a sim ilar increase in the charcoal curve. areas between tropica l ra inforest and
responsible. at least In part. for the However. the pollen record et Lake sclerophyll vegetation prior to 38 .000 years
proliferation of eucalypt forests which George is not as deta iled as that of the ago. manage to survive these earlier dry
dominate the Australian landscape today. Atherton Tableland. wh ich. because of Its periods and yet suffer so drast ically In the last
Ana lysis of pollen samples from the high t em perat ures and heavy rainfall . one7
Atherton Tableland in nort h Queensland by contains a rich variety of vegetation types The answer. Kershaw believes. probably
Dr A . Peter Kershaw. of the Monash including rainfo rest comparable in diversity lies in the int roducti on of the additional fac
geography department. shows a dramatic with any to be found in the world's tropics. tor. Abo riginal man. who is known to have
changa in the Australian lendscape over the Kershaw obta inad cores of accumulated been present in Austral ia for at least 36 .000
past 120.000 years. organic mata rial from several locations in years.
Much of the change appears to be dua to sediments that had accumu lated in volcan ic He may. through his activ ities. have
variat ions in climate . but the dom inence of crater lakes inland from Cairns. increased the level of burning to a point
lerophyll vegetation. indicated by tha high The cores were taken to a depth of 46 crit ical to the survival of this fire-sensitive
lues of Cesuerlna and Eucalyptul pollen metres . and have permitted pollen " map vegetation. already under stress from the
in the pollen record. begins about 38.000 ping" over a lengt hy period . decline in rainfall.
years ago. By then . it Is believed. the " Pollen extracted from the cores was Although the impact of the Aborigines on
Aborigines had arrived in Australia . orig inally derived from plants surrounding the the environment was significant. the max
The emergenca of the sclerophylls - par lake: ' Kershaw expla ins. " Therefore the imum fir ing of forests does not appear to
ticularly the fira -tolerant Eucalyptus - as pollen composition of each sample Is a have occurred until the arrival of the
the dominant vegetation coincldas w ith a raflection of the natu re of the vegetation Europeans.
decrease in rainfall and a massive increase in growing around the lake at the time of the The Lake George research shows that
charcoal particles - an indication of the sample 's eccumu lation. charcoal revels after the arrival of the
increased prevalence of fire . " Variati ons in the pollen from sample to Europeans initially reached more thsn 3~
Kershaw believes that the "sharp Increase sample record changes in the vegetation times that of the highest level in the
in the charcoal curve" . wh ich has been from time to time ." Aboriginal period and more than 16 times
mainta ined to the present day. Indicates that Kershaw has Identi fi ed four dist inct the peak levels of natura l fires In the earlier
the increase in fires at th is time was due periods from the pollen racord In this region inter-glecials.
largely to the activitias of man - the use of over t he past 120.000 years: Ke rshaw 's work . wh ich has been
fira by Abo rig ines for hunt ing and easier • From 120.000 to 80.000 yeare ago. cont inu ing for 10 years. Is partly aimed at
trave l. rainforest angiospe rms (flowering plants) providing an hlatorlcel perspect ive for people
Tha role of Abor iginal man in chang ing the - sim ilar to those composing the comp lex Invol ved In the management of forut
landscape of Australia Is supported also by trop ical rainforest existing over much of resources.
research at Lake Gaorge in NSW . wh ich the Athe rton Tableland today - were "If you have an understanding of the
pushes the pollen record back even further dom inan t. At that time the cllmata was natu re and clluses of vegetation changss
to about 360.000 vears ego. probab ly very similar to that of today . w ith in an area: ' he says. " It provides a
The Lake George research. by Aus tralian • From 80 ,000 to 38 .000 years ago. realist ic basis for edoptlon of management
Nat ional University pollen enalyst Dr G. Araucarls forest con taining abundant strateg ies wh ich w ill allow the survlval of
Singh, shows a similar amergance of the gymnosperms (conifers) covared much of desired commun ities In the long term ."
Eucalyptus as the dom inant vegeta tion in the Tableland . This vegetat ion type occurs The resaarch has been supoorted by
ralat ivaly recant tlmee of the late Quaternary extens ivelv in south-eastern Queensland ARGC and Monesh Special Resesrch Funds.
MON ASH REVIEW 5 JUNE
chloramphenicol resistance is encoded on a
Antibiotic resistance plasmid. All the " Golden Staph " strains
examined were resistant to methicillin. Some
were resistant as well to either gentamicin or
chloramphenicol. Others were resistant to
both of the antibiotics.
Bacteria often cont ain several plasmids of
varying size. The "Golden Staph " strains
isolated from the Royal Children's Hospital
contained. in some cases, three plasmids
one encoding resistance to chloram phenico l,
one to gentamicin. and a th ird, whose
THE emergence of bacterial strains function has not been deciphered.
resistant to almost every usable antibiotic " W e expect to find further examples of
is causing grave concern in many plasm id-born antibiotic resistance in both S ,
Melbourne hospitals, according to Monash Aureus and S. Epidermldis," 5kurray says.
microbiologist, Dr Ron Skurray. An important part of the research is the
He says strains of Staphylococcus attempt to understand how antibioti c
Aureus. commonly known as " Go lden resistant pla sm ids originated and how the
Staph", the most dangerous member of the resistance is transferred to other strains.
staphylococcal group, are now resistant to One possib ility is that antibiotic resistance
pen icillin, ampicillin, methicillin. cephalothin. may have been introduced into the plasmid
kanamycin , gentamicin. tobramycin , co on a transposon, a small piece of DNA which
trimoxazole. chloramphenicol. tetracycline has the ability to insert itself at specific points
and erythromycin. on a plasmid; Melbourne staphylococcal
As well. several strains isolated from , ~ lL· ~<. strains are being examined for transpose
patients at Prince Henry's and St Vincent's Ph ,D. student Bruce Lyon loads "Golden by Skurray and May.
Hospitals have shown resistance to fus idic Staph " plasmid DNA on to an agarose gel for Skurray believes that in the case of
analy sis. Mon ash mIcro-b iologists Dr Ron Sk ur
acid and rifampi cin , two of the th ree ray and Or John May are attempllng to estab lish staphylococci. resistance. once established in
remain ing antibi ot ics available for use. the genetic basis for (he rapid emergence and the plasmid, is transferred from one
spread of mull/pie antibiotic resistance, which Is
" T h e only remaining antibiotic. caus ing concern in Melbourne tiosottets. bacter ium to another either by transduction
vancomycin. now forms the mainstay of Phot o: Rick Cromp ton . or transformation.
treatment in many hospital units and , while In transduction. the bacterium is invaded
not yet reported, resistence to th is antibiotic resistance is transferred among staphvlococ by a bacteriophage. a bacteria-attacking
may emerge," he says. cal stra ins. virus , wh ich incorporates a small portion of
Skurray and Dr John May, senior lec The research is being conducted in the bacterial DNA within itself and escapes
coll aboration w ith Dr Tim Humphrey, of with it when it causes the bacteria to burst
turers in the Monash mi crobiology depart
ment. are attempting to establish the genetic Prince Henry's Renal Unit and Dr John open.
basis for this rapid emergence and spread of Andrew, Director of Microbiology at St The bacterial DNA is introduced into other
multiple antibiotic -resistance as an aid to Vincent's Hospital. bacteria when the virus subsequently infects
more rational use of ant ibiotics. Skurray says ant ibiotic resistance can be them. The introduced DNA may include the
Recent studies at several Melbourne encoded either on the main chromosome of antibiotic resistance. The Monash team is
hospitals underline the gravity of the the staphylococcus, or on a small , cir cular screening "Golden Staph " stra ins for
situation. A study in the renal unit at Prince piece of DNA (genetic material) called a transdu cing-type bacteriophages.
Henry's Hosp ital has shown that approx plasmid. which can be obtained in the Transformation, the second method, is the
imately 250 days of hospitalisation from laboratory separate from the chromosome. uptake of " n aked" DNA by a bacterium.
peritonit is in ambulatory dialysis patients can As well as contain ing genes for the ir own When a bacterium dies it bursts open, spilling
be blamed on antibiot ic-resistant maintenance, plasm ids can carry genes for a out its DNA. including the plasmid. which
staphylococci. number of properties besides ant ibiotic may be taken up by nearby bacteria.
At St Vincent's Hospital 50 patients a day . resistance . These in clude resistance to heavy
Skurray says there is a third method .
on average . are either infected by multiple metals. toxins, and, in some cases, genes
transfer. a sexual -type of transfer called
resistant " Go lden Staph" or harbor it as car which enable the plasmid to be transferred to conjugation, which occurs in Escherichia
riers. Furthermore, it is estimated that in ma other closely related bacteria. coli, a bacterium which inhab its the human
jor Melbourne hospitals approximetely 70 Recent studies by Skurray and May of gut.
patients a day are unable to be discharged " Golden Staph" isolated from the Royal It was thought that in thi s method. DNA
because they are " Go lden Staph" carriers , Children 's Hosp ital show that gentamicin and was transferred through a tube -like stru cture
" In addition to the difficulties associated called a pilus, on the su rface of " donor"
with the specialised nurs ing of these patients bacteria which attaches to the " female"
necessary to prevent cross-infection," Skur during conjugation.
ray says. " the economic burden imposed by It is now believed that the pilus is more
bed occupancy is estimated to be approx like a grappling hook, Skurray says, It
imately $1 million per year in Melbourne." interacts with a receptor on the surface of the
Skurray's and May's research is eimed at: recipient cell. then retracts, drawing the two
• Identifying the way in which antibiotic bacteria into close contact. A bridge is
resistance is encoded in S. Aureus and also formed. and a single strand of plasmid DNA
in S. Epldermidls . The latter is a less is transferred across.
dangerous relative of the "Golden Staph" Conjugation is common in enteric
and is commonly found on the skin . S. bacteria, Skurray says, but it has never been
Epidermldls has also shown a disturbing observed in staphylococci.
tendency to develop multiple antibiotic "U ndersta nding how antibiotic resistance
resistance and it may act as a gene pool to is spread and how resistance to different an
spread resistance emong the more invasive tibiotics is linked should help in establishing a
" Golden Staph" strains. more rational approach to the use of an
• Establishing patterns of linked tib ion cs," he says.
resistance to several antibiotics, end " It should also be possible to monitor the
• Examin ing the way in which antibiotic Dr Ron Skurray emergence and spread of resistance to
MONASH REVIEW 6 JUNE
Continued from Page 6
newly-developed antibiotics through our
Enzyme 'marker' aids
Parallel to the "Golden Staph" research,
Skurray is using recombinant DNA
technology (genetic engineering) to explore
the genetics of part of the "F factor", the
plasmid in E. Coli. which is responsible for
" A considerable amount is known about
conjugation in E. Coli and the genes involved MONASH researchers at the Alfred
are well characterised. However, the part we Hospital have made an important advance
are examining is genetically uncharted," he in the management of patients suHaring
says. from tho blood disorder. non -Hodgkins
H is group has cut the " F factor" region of
interest into small fragments using restriction
enzymes, chemicals which slice DNA at
They have identified a biochemical
" marker" in the lymph glands and blood of !
specific sites . these patients which enables them to predict Clinical Associate Professor M. 8. Van der
the degree of "aggressiveness " of the Weyden (right) and Dr T. E. Gan in the process of
The fragments have been cloned on to a purifying the enzyme, foetaf thymidine k inase .
series of plasmid vectors and inserted into E. disease and choose the most suitable The enzyme serves as a "marker" which
Coli bacteria. Smaller pieces will be cloned treatment. enables them to predIct the degree of "ag
gressiveness " of the blood disorder, non
on to other plasmid vectors, and the genetic Non-Hodgkins Lymphoma is marked by Hodgkins Lymphoma.
and biochemical properties of the "F factor" proliferation of lymphocytes (white blood Photo: Rick Crompton.
' ·qgments will be determined. cells) and enlargement and "distortion" of
with the best prognosis is "diffuse well
the lymph glands .
differentiated lymphocytic lymphoma".
In some ways . it is similar to Hodgkins
Patients with this form of lymphoma, who
Disease. but the type of lymphocyte affected
have the " adult" type of the enzyme, live a
Gentamicin plasmid is different and the age of onset differs also.
long time. Van der Weyden says. " They can
Hodgkins Disease usually strikes young
Chromosom e have a normal life-span if the disease can be
people in the 15-30 age group or the elderly.
controlled by chemotherapy and
Non-Hodgkins lymphoma is a disease of
radiotherapy." he says.
Chloramphenicol plasmid middle and later life .
At the other end of the scale are patients
(Form 1) The biochemical " marker" isolated by the
with diffuse histocytic lymphoma who have a
Monash team , Clinical Associate Professor
more "prol iferative and prognostically
M .B. Van der Weyden, Drs P. H. Ellims
unfavorable disease". These patients have
and T. E. Gan. is an enzyme , thymidine
the " foetal" form of the enzyme.
kinase. which is involved in the multiplication
There is a whole gradation between. Some
pat ients, with the " adult" form of the
If thymidine kinase is present in an "adult"
enzyme, need not be treated at all. They need
form in the lymph glands and lymphocytes of
Cryptic plasmid only be watched in case the disease starts to
patients suffering from non-Hodgkins
proliferate and the " adult" form of the
Lymphoma. it is an indication that the
Agarose gel, after staining and illumination with enzyme is transformed into the "foetal" form.
ultraviolet light, shows bands of "Gorden tumour is slow-growing and may not even
The Monash team has studied 45 patients
Staph " DNA , with ptssmtds, which carry genes need treatment.
for resistance to various antIbIotics. The strain at the Alfred and Prince Henry 's Hospitals
(left) was Isofated from a patient at the Royar
If it is present in the "foetal" form. it
over the past five years. The team has found
Children's Hospital; (r ight) from Prince Henry's indicates that the tumour is fast -growing and
HospItal. that . while it is not possible to form a
intensive radiotherapy and chemotherapy is
prognosis on " established parameters" . such
These cloned fragments have been used needed.
as age . symptoms or bone marrow
probes to unravel the role of messenger Van der Weyden and his colleagues have
involvement. it is possible when the patients
RNA (mRNA) in the "F factor" fragment. developed a simple test, which can be done
are divided into groups accord ing to the
mRNA is involved in the manufacture of in any biochemical laboratory. to detect the
presence of either the " adult" or "foetal"
protein and the Monash team has shown that presence of this enzyme in its differing forms.
forms of the enzyme in their lymph glands
mRNA is made from this region. They are The " adult " form utilises adenosine
and blood sera.
now looking at proteins corresponding to the triphosphate (ATP) and cytidine triphosphate
The team found that the group with the
mRNA. in its metabolism. The "foetal" form , which
"adult" form of thymidine kinase had a mean
Skurray stresses that there is no danger indic ates a rapidly developing disease ,
survival rate in excess of 400 weeks . Where
from the genetic engineering techniques that utilises only ATP.
the "foetal" form of the enzyme was present
he is using to map the " F factor" genes. " W e have demonstrated that there is a
in the serum or lymphocytes, the mean sur
" W hat we are doing is nothing more then progressive increase in activity of the
vival rate was one year.
what has occurred previously in nature." he enzyme. thym idine kinase. as you go from
The Monash team has found that the
says. " W e are not making any hybrid bacteria patients with a slowly progressing to a rapid
enzyme " marker" is a valuable aid also in the
or creating any combinations that don 't ly progressing form of the disease ," Van der
management of chronic lymphocytic
already exist. Furthermore, the E. Coil strain Weyden says.
leukaemia . a slowly-developing form of
we are using for cloning is so enfeebled that The problem of diagnosis and treatment of
leukaemia which occurs in older people .
it can only exist for a short time in the human non -Hodgkins Lymphoma is complicated by
the fact that there are different forms of the Because of the slowly-developing nature
of the disease . the age of onset and the
" W e are not using recombinant DNA disease.
unpleasant side -effects of modern
technology in our work on staphylococci, and Two major sub-groups have been
chemotherapy . some doctors have
we have no plans to use it until we know identified by histological techniques: nodular
questioned the need for treatment of chronic
more about the plasm ids and the genes they non-Hodgkins lymphoma, in which the
carry." disease is usually disseminated but is slowly
But the Monash team has identified two
The staphylococcus and " F factor" progressing , and diffuse non-Hodgkins
sub-groups of the disease : one , in which the
research is being funded by Monash Special lymphoma, in which it is localised but has a
" adult" form of thymidine kinase is present,
Research funds and the Australian Research " highly proliferative capacity."
Grants Committee. The form of non-Hodgkins lymphoma Con tin ue d overleaf
MONASH REVIEW 7 JUNE
Physiologist Dr Magda Weiss (r ight), ess ist ed by
Hormone technical officer Mrs Val Ford, s ep arati ng
adrenal zones of the brusti-teited p ossum. She
has found thal lh e female possum has a special
zone In the adrenal cortex with a different hor
clues to mone pattern to that of adult males and im
mature an imals.
Photo: Rick Crompton .
tals ," Weiss says, " w ould seem to be a more
marsupial appropriate adaptation, enabling the animal
to adjust more rapidly to env ironmental
evolution A puzzling feature to emerge from the
research is the discovery that there is a sex
and age difference with regard to an enzyme
AT one time the placental animals which metabolises and inactivates steroids.
the dominant mammalian species - were This enzyme , called a reducing enzyme, is
thought to be more advanced on the usually found only in the liver . In the possum
evolutionary tree than the marsupials. hormones [steroids} which are involved in it is found also in the adrenal gland of the
The marsup ials ware considered ancestral salt metabolism and the metabolism of adult female.
to the placentals, energy reserves. Its activity is very high in the adult female
The present opinion among evolutionary Weiss's team found that while the bas ic possum : it is almost absent in the male pos
biologists is that this is most unlikely. They adreno-cortical funct ions of the marsupials sum and it is neglig ibly low in immature
favor the view that marsupials and placentals were similar to those of placental mammals, animals of both sexes.
have d iverged from a common ancestry. there were considerable differences Weiss says it has long been known that
In this view, many of the peculiarities of regarding the properties and activities of the the possum is unique among species in that
marsupials are specialisations wh ich have enzymes involved in hormone synthesis and the female'S adrenal cortex, unlike that of t ~
evolved in isolation . They a re not in the responses of the hormones to the male , possesses an additional ar c
characteristi cs that were formerly present in body 's various regulatory systems. composed of specific cells referred to as the
the ancestry of placentaIs. Some of the endocrine features were special zone. This special zone is also absent
The most striking difference between mar peculiar to marsupials as a class, such as the in the adrenals of immature possums.
sup ial and placental mammals is in the way synthesis of unique steroids , but there were " The special zone varies in size during the
tha embryo develops. also significant interspecies differences. reproductive cycle , pregnancy and lactation,"
The marsupial embryo is born in a very Because the adaptations appeared to be Weiss says. " At times it can occupy as much
immature form and completes its most marked in the brush -tailed possum , she as 75 percent of the total VOlume of the
development in the mother's pouch. has used this marsupial to explain her gland ."
In placental animals , on the other hand . findings. Weiss and her team dissected the special
the foetus is nourished in the uterus, through "In the early stages of our investigations zone from the cortex proper to determine
the placenta , until development is far we discovered that the adrenal venous blood
steroid synthesis. A remarkable picture
advanced. of the possum contained numerous unusual emerged.
Monash physiologist Dr Magda Weiss. st eroids :' she says. " Som e of these steroids Wh ile the steroid pattern of the cortex
assisted by technical officer Mrs V. L, Ford we re intermediates in the biosynthetic proper was sim ilar in the female possum to
and postgraduate students, has now pathway. One stero id (Z1-deoxycortisol) is that of adult males and immature animals,
discovered endocrine differences between not found in healthy placental mammals, but the pattern in the special zone was not. It
marsupials and placentals wh ich are just as it has been found in patients with a specif ic produced reduced steroids.
striking, and are important in understanding enzyme deficiency. "lt is obvious that the female possum has
the marsupial's evolution and adaptation to "This discovery prompted us to undertake undergone a unique type of adaptation: '
its environment . Har findings are the result of in-depth investigations into the properties of Weiss says. "A specific area of the adrenal
15 years research on marsupials . the enzyme systems involved in steroid syn cortex has developed in the female which has
Weiss and her team studied the thesis ." the capacity to metabolise the steroid
functioning of the marsupial's adrenal cortex, Weiss found that unlike normal placental formed by the cortex proper .
the outer part of a gland, which , in mammals, mammals wh ich have multiple enzyme " The enzyme responsible may be involved
is related to the animal's ability to adjust to systems. each of which acts on a specific in the adrenal control of steroid synthesis and
environmental change. steroid substrate [substance], the possum 's inactivation."
The adrenals are small glands located adrenal enzymes are "non-substrate One of her future tasks will be to elucidate
above the kidneys. They are composed of an specific". They act on any steroid substance the rote of the enzyme .
inner part. called the medulla, and an outer supplied to it . "Experimental data so far suggests that
part, called the cortex. The cortex is essential Weiss believes the multiple enzyme there is an involvement of the ovaries in the
for the maintenance of life since it produces systems of the placental mammals give them control of the size of the zone:' she says.
an advantage over the marsupials, enabling " Our research is aiming in that direction.
finer control of biosynthesis, as well as an in
Lymphoma dividual response to regulatory systems, and
prov iding a safeguard if one of the enzymes
"A more difficult task however will be to
find out what could be the physiological role
of these reduced steroids which are
Continued from Page 7 becomes defective. synthesised only in the adult female pos
Placental mammals, apparently, also have sum.
and the other, in which the "foetal" form of an advantage in their react ion to en Weiss says some features of the adreno
the enzyme is present. vironmental stress . cortical function of the possum seem
When the "adult" form is present, the Stress usually induces a rapid rise in the " inferior" in the evolutionary sense and soma
disease is relatively dormant. Where the synthesis of steroids. Cortisol is a well-known are difficult to explain.
" foetal" form is present it is rapid in "stress" steroid. Increased quantities of cor She believes however that they probably
developmant. and, according to Van der tisol are found in the blood plasma and urine have a " definit e selective value" which has
Weyden , needs early and intensive of people subjected to stress . enabled the marsupials to survive in
treatment. Weiss found that in the possum the rate of conjunction with placenta Is under similar en
The Monash research has been published steroid synthesis was only one hundredth to vironmental conditions.
in Cancer Research and was funded by the one thousandth that of placental mammals The research is funded by an ARGC grant.
Anti-Cancer Council of Victoria and the and that during stress the rise was sluggish
National Health and Med ical Research Coun and of lesser magnitude than in placenta Is. Pnn ted by Stand ard Newspapers for
cil. "The faster stress response of the placen MonaSh University
MONASH REVIEW B JUNE