Chocolate Astrobiology AIDS 25 Years On

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Issue 5    Lent 2006                                         

                                                     The search for alien life

AIDS: 25 Years On
Past, present and future

Why do we love it?

                   • Grapefruit • Dr Hypothesis •
                • Probiotics • Quantum Computers •
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Issue 5
Lent 2006

Feature s
             Quantum Calculations
             Tristan Farrow introduces the computers of the future.................................................................                10
             DNA Damage and Repair
             Zoe Smeaton highlights a Cambridge scientist s efforts to revolutionize cancer treatment..                                            12
             Chocolate s Chemical Charm
             Dhara Thakerar explains the science of chocolate...........................................................................           13
             Are We Really Alone?
             Gemma Simpson explores the universe for possible signs of life.................................................                       14
             Probiotics: More Pros than Cons?
             Louise Woodley on the benefits of ingesting live bio-cultures.......................................................                  16
             The Sixth Sense
             Juliette McGregor uncovers the artwork we never knew we could see, Haidinger s Brush..                                                18
             Citrus Paradisi
             Chi Ngai Chan examines the link between grapefruit juice and Viagra.......................................                            19
  Regulars   Editorial .............................................................................................................................. 03
             Cambridge News ............................................................................................................. 04
             Focus ................................................................................................................................... 06
             On the Cover ................................................................................................................... 20
             A Day in the Life of... ...................................................................................................... 21
             Away from the Bench ..................................................................................................... 22
             Initiatives ............................................................................................................................ 23
             History ............................................................................................................................... 24
             Arts and Reviews .............................................................................................................26
             Dr Hypothesis .................................................................................................................. 28

             The cover shows a carbon nanotube with magnetic Cobalt-Palladium crystals at the end.The magnetic field it induces
             has been mapped by taking an electron hologram with a Transmission Electron Microscope.The colours correspond
             to the direction and intensity of the field, and field lines have been overlaid.Taken by Ed Simpson, High-Resolution
             Electron Microscopy, Department of Materials Science and Metallurgy.To find out more, turn to page 20.
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                                                                                                                 Issue 5: Lent 2006
                                                                                                                 Produced by CUSP &
                                                                      From                                            Published by
                                                                                                                Varsity Publications Ltd
                                                                 The Editor                                   Editor: Tamzin Gristwood
Welcome to the fifth edition of BlueSci.         have turned to scientists in their attempts               Managing Editor: Louise Woodley
   Did you over-indulge in festive choco-        to save historic pipe-organs across Europe.               Submissions Editor: Ewan Smith
lates this holiday season? If so, you can ease      Of course, the much-loved DR HYPOTH-
those feelings of guilt by reading about the     ESIS is back on page 28 to answer your sci-
                                                                                                           Business Manager: Chris Adams
science behind the reported health bene-         ence-related questions. In addition, new                       Design and Production
fits of chocolate in CHOCOLATE’S CHEMI-          for issue 5, the good doctor has a logic
CAL CHARM. If this whets your appetite for       puzzle for you—to get those grey cells                            Production Manager:
more food-related science, on page 19,           working! The solution is available on our                            Jonathan Zwart
Chi Ngai Chan highlights the startling           website,, where you can                              Pictures Editor:
effects of grapefruit juice on drug metab-       also find extra articles.                                               Sasha Krol
olism, and in PROBIOTICS: MORE PROS                 Once again, we were impressed by the                             Production Team:
THAN CONS? we question just how bene-            quality of submissions we received for                    Sheena Gordon, Jon Heras, Ryan Roark,
ficial those ‘friendly bacteria’ really are.     issue 5, from students and post-docs across                   Helen Stimpson,Tom Walters
   To coincide with the 25th anniversary of      the University. If you feel you have what it
the first recorded case of AIDS, our regular     takes to write for BlueSci, or you wish to                            Section Editors
FOCUS section examines the current status        get involved in editing or producing the                               News Editor:
of HIV and AIDS research, and looks              magazine, we would love to hear from                                  Fiona McCahey
ahead at what the next 25 years may yield.       you: either email or                       News and Events Team:
   In ARE WE REALLY ALONE?, Gemma                visit BlueSci Online for more details.                       Laura Blackburn, William Davies,
Simpson turns to the field of astrobiology          I hope you enjoy reading issue 5.                      Michael Marshall, Richard van Noorden,
to look for evidence of alien life-forms,                                                                                Emily Tweed
while in PROBLEMS IN THE PIPELINE, Mark                                      Tamzin Gristwood                               Focus:
Turner explains why organ enthusiasts                                      Tamzin Gristwood, Jonathan Zwart
                                                                                                            Laura Blackburn, Margaret Olszewski,
                                                                                                                Bojana Popovic, Ewan Smith
                                                                                                                       On the Cover:
                                                                                                                        Victoria Leung
                                                                                                                   A Day in the Life o f :
                                                                                                                       Louise Woodley
                                                                                                           Away from the Bench and Initiatives:
                                                                                                                        Kathryn Holt
                                                                                                                     Varsha Jagadesham
                                                     From                                                            Arts and Reviews:
                                                                                                                       Owain Vaughan
                                       The Managing Editor                                                             Dr Hypothesis:
                                                                                                                          Rob Young
Happy New Year! Things have been very            positive feedback, as well as learning about                     Lizzie Fellowes-Freeman
busy for BlueSci over the past few months.       other science communication projects
                                                                                                                      CUSP Chairman:
Our first birthday party was a big suc-          across Europe. See for
                                                                                                                         Bj rn Ha§ler
cess—many thanks to all who came. Partly         some photos and videos of our stand!
as a result of this, Nicola Buckley, one of         Finally, this issue sees the addition to                             ISSN 1748-6920
the Cambridge Science Festival coordina-         BlueSci Online of our news and events                        
tors, has set up an informal science out-        service, which will be updated fortnightly
reach group which has since met to discuss       with Cambridge science stories, as well as
how we can unify our efforts to reach out        having a comprehensive listing of science-
to local schools. If you would like to join      related events. Please bookmark our web-                          Varsity Publications Ltd
us,    please      contact    Nicola     at      site and remember to check                       11/12 Trumpington Street                         regularly for what’s going on.
  BlueSci was also represented as part of           Have a scientifically enlightening 2006!                       Cambridge, CB2 1QA
our parent society CUSP at the                                                                                       Tel: 01223 353422
Communicating European Research con-                                          Louise Woodley                         Fax: 01223 352913
ference (CER2005) in Brussels in                                       
November. We received some extremely                                                                      
                                                                                                     BlueSci is published by Varsity Publications Ltd and printed by
  Next issue: 28 April 2006                                                                        Cambridge Printing Park. All copyright is the exclusive property of
                                                                                                   Varsity Publications Ltd. No part of this publication may be repro-
  Submissions Deadline: 5pm, 20 February 2006                                                       duced, stored in a retrieval system or transmitted in any form or
                                                                                                      by any means, without the prior permission of the publisher.                                                      luesci                                                                                   03
Cambridge News
                                                                    Cambridge News
                                Cambridge’s Computers and CERN                                            WHOLEheart
                                Since 2001, the University of Cambridge has been one of 19                How does the food you eat affect your health? If you would like
                                UK universities collaborating with the European Organization              to find out, researchers at the MRC Dunn Human Nutrition
                                for Nuclear Research (CERN) to construct the GridPP—a vast                Unit in Cambridge are currently recruiting for WHOLEheart,
                                computing grid built to handle the extensive amount of data               a study into the effect of carbohydrates on the body, including
                                that will be produced by CERN’s new particle accelerator, the             blood cholesterol levels and heart health. Scientists at the Unit
                                Large Hadron Collider (LHC).                                              work on all aspects of human nutrition, from the health of our
                                   The LHC is expected to be ready in 2007. It is being built in          bones to nutritional epidemiology.With around 200 studies on
                                a circular underground tunnel, 27 kilometres in circumference,            the go at any one time, the Unit relies on an army of volunteers
                                straddling the Swiss and French borders. When completed, it               to help determine if we really are what we eat. In collaboration
                                will be the largest particle accelerator in the world and will be         with other organisations such as the Food Standards Agency and
                                used to replicate conditions similar to those present shortly after       the EU the Unit also works to reduce public confusion by pro-
                                the Big Bang. It is hoped that it will resolve many outstanding           viding sound nutritional advice to the media, food industry,
                                questions in particle physics, such as whether the hypothetical           government, and health professionals. In collaboration with the
                                Higgs boson actually exists. If it does, it would aid the under-          University of Newcastle, the WHOLEheart study will run
                                standing of why fundamental particles—such as quarks and neu-             through to February 2007. “We hope that we will be able to
                                trinos—have the masses they do.                                           develop a positive public health message to inform people what
                                   The University of Cambridge has been a key collaborator in             they should be eating” says Katherine Chan, who is recruiting
                                the construction of the GridPP. Rather than build a dedicated             for the project. If you are interested, contact katherine.chan@mrc-
                                supercomputer to deal with the 10 million gigabytes of data that or 01223 437660 for more information. LB
                                the LHC is expected to produce each year, a distributed Grid is
                                being constructed. Over 100,000 PCs around the world are
                                being linked together to form the Grid PP; of these, 1000 are in            Do you want to meet a qualified nutritionist? As part of
                                the UK. The Cambridge effort is being headed by Professor                   Cambridge Science Week, you will have the chance to meet
                                Janet Carter of the Cavendish’s High Energy Physics group.                  a panel of qualified nutritionists for no nonsense, simple
                                MM                                                                          advice on what to eat. 5 pm, Saturday 18 March 2006,
                                                                                  Michaelhouse Café.

                                Cambridge University Scientific Society – Michaelmas 2005 Talks
                                Professor Sandra Chapman: Art Meets              between the hostile climate and beautiful-      that have captured many an imagination,
                                Science in Antarctica                            ly unspoilt landscape. We were treated to       yet which under the surface, are often
                                An astrophysicist by training, Professor         the most charming of travelogues from a         opaque. Professor Michael Green, widely
                                Sandra Chapman demonstrated her fine             truly unique personality, whose insight         known for sparking the First Superstring
                                hand for art and keen eye for photography        into the interplay of science and art was       Revolution in 1984, presented the Society
                                in a talk with a difference. Last year, she      delightfully refreshing.                        with a wonderfully clear introduction to
                                realised her dreams of travelling to                                                             string theory, from its beginnings as a
                                Antarctica by circling the continent             Professor Tom Mullin: Patterns in the           mathematical convenience to the cutting-
                                aboard a research ship. During her expe-         Sand (pictured)                                 edge of today and its far-reaching implica-
                                dition, she masterfully captured the bril-       Introduced as the world record holder for       tions. Let us all be grateful that of the 26
                                liant blue of ice caves, the pale pink of dis-   stacking the greatest number of upside-         dimensions he described, it seems we need
                                tant mountains, and the connection               down pendulums, Professor Tom Mullin            only negotiate four.
                                                                                 attracted a huge crowd.The segregation of                                     Cong Cong Bo
                                                                                 granular mixtures is relevant not only to
                                                                                 physicists, geologists and engineers, but
                                                                                 also lovers of muesli: the Walnut Effect         All talks are held in the Pharmacology
                                                                                 explains why shaking your cereal box ver-        Lecture Theatre, Tennis Court Road.
                                                                                 tically will make the fruit rise, while shak-    More details are available on our web
                                                                                 ing the box horizontally will make it sink.      site have a great line-
                                                                                 Professor Mullin is internationally              up of speakers for next term, including:
                                                                                 acclaimed for his work on the application        Pioneering embryologist Dame Anne
                                                                                 of modern mathematical ideas to chaos            McLaren of the Wellcome Trust and
                                                                                 and complicated flows. He has most               Cancer Research UK Gurdon
                                                                                 recently investigated the flow of granular       Institute, speaking on human cloning;
                                                                                 materials such as sugar and poppy seeds,         Cosmologist Dr Martin Bucher of
                                                                                 revealing a rich variety of novel and            Université Paris-Sud, discussing dark
                                                                                 intriguing phenomena.                            energy; Psychologist Dr Peter
                                                                                                                                  Thompson, Director of the Visual
                                                                                 Professor Michael Green FRS: String              Perception Library and originator of
                 Cong Cong Bo

                                                                                 theory: Unifying Particles, Forces and           the Thatcher Illusion; Accomplished
                                                                                 Space-time                                       botanist Professor Peter Crane, Director
                                                                                 Quantum physics. String theory.That oh-          of Kew Gardens.
                                                                                 so-elusive grand unified theory. All topics

                                 Congratulations to one of the Bluesci news team, Dr William Davies, for winning first prize in the National Brain
                                 Science Writing Prize. His winning article Battle for the Brain can be viewed at

      04                                                                                       luesci                                                         Lent 2006
                                                                                                                                                                         C a m b r i d g e N ew s
             Matangini Project
             Around 200 million people worldwide suffer from schistoso-
             miasis, a debilitating and sometimes fatal disease caused by par-
             asitic worms which affect many parts of the body, particularly
             the liver, intestine and bladder.The Matangini project has been
             set up by the Department of Pathology’s Schistosomiasis
             Research Group to give something back to the communities
             in which they study the immunology and epidemiology of the
             disease.“After each survey, we have a whip round to buy some-
             thing for the community where we were studying” says Dr
             Mark Booth, who helped found the project. “However we
             wanted to find a more sustainable way of raising income for
             these communities.” One of the initiatives of the Matangini
             Project is a photo-gifts website, selling products containing

                                                                                                                                                         John Hillier
             African photos taken by Dr Booth.The first community proj-
             ect will be to dig a borehole with a pump in a community in
             Kenya, providing clean water free from water-borne diseases
             including schistosomiasis for over 2000 people. “Our next
             project is to raise money for a container fishing boat for a        Piggyback Volcanoes
             community in Uganda” he says.The group has studied some of
             these communities for over 30 years and often treats children       Young volcanoes in French Polynesia, in the south-central
             of the people who were involved in the study when it first          Pacific Ocean, could form by ‘piggybacking’ on older, otherwise
             began. Using a multidisciplinary approach, the group is             unrelated volcanoes, according to new research by Dr John
             researching many aspects of schistosomiasis, including trying to    Hillier in the Department of Earth Sciences. He has created four
             find out why some people are more seriously affected than           new maps of the Pacific Ocean that illustrate where volcanoes
             others by the disease. LB                                           have erupted in the last 160 million years. To do this, he dated
                                                                                 2700 of the approximately 50,000 large volcanoes in the Pacific
              To support the Matangini project, visit and   using a map of gravity variations, which was derived by measur-
                                      ing the sea-surface height, and seafloor depth from ship-based
                                                                                 sonar measurements. The height of each volcano was found
                                                                                 using MiMIC, an algorithim that Dr Hillier developed during
                                                                                 his PhD.The height of a volcano, when compared to the gravi-
                                                                                 tational pull of the volcanic mass, relates to the age of the vol-
                                                                                 cano. Using this method, ten times more volcanoes have been
                                                                                 dated than by collecting rock samples. In some notable volcanic
                                                                                 chains, neighbouring volcanoes are separated in age by tens of
                                                                                 millions of years.“Generally, neighbouring volcanoes are expect-
                                                                                 ed to be of a similar age,” explained Hillier.“Hawaii, for instance,
                                                                                 is the youngest island of a chain of volcanoes which get older to
                                                                                 the northwest implying that the Pacific tectonic plate is passing
                                                                                 over a source of molten rock.” However, his results show young
                                                                                 and old volcanoes alternating in chains such as the Cook-Austral
                                                                                 Islands. Both the young and old volcano age groups exhibit an
                                                                                 age progression along the chain, indicating a causal link between
                                                                                 the formation of the volcanoes at different times. “These more
Mark Booth

                                                                                 complex eruption patterns are an excellent window into why
                                                                                 the Earth melts and how the molten rock forces its way through
                                                                                 the tectonic plate to the surface,” explained Hillier. FM

             Why Darwin proves that your undergraduate years are the most important
             It is widely believed that the seeds for                                                   of his collaborators on the herbarium and
             Charles Darwin’s theory of evolution were                                                  also arranged his place on HMS Beagle.
             sown during his famous trip on HMS                                                         Professor Parker and colleagues have found
             Beagle. However, new research by Professor                                                 evidence to suggest that on HMS Beagle
             John Parker, Director of the Botanic                                                       Darwin began looking at plants and ani-
             Garden at the University of Cambridge,                                                     mals using the conceptual framework he
             and colleagues suggests that Darwin’s evo-                                                 had absorbed from Henslow. Though
             lutionary thinking may have had its foun-                                                  Darwin’s assumptions were later to change,
             dations in the teaching he received during                                                 Henslow’s instruction was a vital influence
             his undergraduate years (1829–1831). In                                                    in his noting of species variety. It formed
             their article in Nature, the researchers                                                   the basis for his eventual understanding
             explain that one of Darwin’s lecturers dur-                                                that varieties are in fact ‘new-forming’ (i.e.
             ing that time was the botanist John                                                        evolving) species. “It’s a great example of
             Henslow, who is famous for his rigorous                                                    how influential teaching can be in forming
             and extensive research into the nature of                                                  the mind of the undergraduate. This
             plant species. He assembled a herbarium of                                                 undergraduate teaching certainly launched
             over 10,000 plants and organised them                                                      Darwin with the ability to think for him-
             uniquely in order to emphasize variation                                                   self about the nature of species” said Parker.
             within species—though believing, as                                                        RN
             everyone else did, that species were created                                                             Nature, 436: 643–645 (2005)
             and stable. Henslow enlisted Darwin as one                                                                     

                                                  luesci                                                                                      05

                     AIDS: Past, Present and Future
        2006 marks the 25th anniversary of the first recorded case of AIDS. Emily Tweed delves into
        the early social impact of the disease. Opposite, find out exactly how HIV operates. Over the
        page, we sketch the effect HIV is having on society today and Collette Altaparmakova looks
        at the prospects for future research.

        The year is 1981 and the US Centers            drug users, and later in haemophiliacs—         remembers,“There was a lot of sentiment
        for Disease Control and Prevention             people with a disorder in blood clotting        in the early eighties that pandemics were
        (CDC) publish an article by doctors in         who require regular blood transfusions.         not possible in this day and age.”
        New York and Los Angeles reporting a           Scientists at the US National Institutes of        Reports began to filter in of similar
        cluster of unusual diseases among              Health (NIH) began to suspect that an           cases across the world, first in Europe and
        young gay men. The men have unex-              infectious agent, transmitted by blood or       then in Africa, where the disease was
        plained defects in their immune sys-           sexual contact, was to blame.                   known as ‘slim’ due to the extreme
        tem making them susceptible to rare              The spread of the disease to groups           weight loss that occurs in its later stages.
        forms of pneumonia, cancer and fun-            beyond the gay population marked a              This was a time of great public fear. So
        gal infection. Clinicians and scientists       turning point in terms of its public per-       little was known about HIV that confu-
        alike are baffled, and theories abound         ception.As Harold Jaffe of the CDC later        sion was widespread. In the US, a young
        as to the origin of what seems to be           remarked,“Up until then it was entirely a       haemophiliac who contracted HIV
        an entirely new disease.                       gay epidemic, and it was easy for the aver-     through a blood transfusion was banned
           Twenty-five years on, and this disease is   age person to say ‘So what?’ Now every-         from school, whilst in the UK firemen
        estimated to have killed more than 25

        million people. Acquired Immune
        Deficiency Syndrome (AIDS), caused by                           A young haemophiliac who contracted
        the Human Immunodeficiency Virus
        (HIV), is one of the greatest threats to                           HIV through a blood transfusion
        global public health of our time. The                                 was banned from school
        United Nations estimate that 40.3 mil-
        lion people worldwide are currently liv-
        ing with HIV; 4.9 million new infections
        occurred in 2005 alone. In this issue,
        Focus looks at different aspects of the
        AIDS pandemic and the science behind
                                                       one could relate.” The disease revealed
                                                       previously hidden prejudices within soci-
                                                       ety and formed a key rallying point for
                                                                                                       were prohibited from giving the kiss of
                                                                                                       life for fear of contagion.As The New York
                                                                                                       Times reported, “In many parts of the
        the fight against HIV.                         the emerging gay rights movement.               world there is anxiety, bafflement, a sense
           The disease was initially known as             By the mid-1980s, the HIV virus had          that something has to be done—although
        GRID (Gay-Related Immune Disorder).            been independently isolated by Luc              no one knows what.”
        Some epidemiologists speculated that it        Montagnier at the Institut Pasteur in              Since those early years, the world has
        was caused by use of the drug amyl             France and Robert Gallo at the National         seen the pandemic spiral out of control.
        nitrate, common in the gay clubbing            Cancer Institute in the US. Two forms           One of the reasons why the disease has
        scene.The first significant clue to the true   were later characterized: HIV–1,                spread so effectively is that there is a long
        nature of the illness was the discovery of     accounting for the majority of infections       delay between infection with HIV and
        similar symptoms in a group of injecting       worldwide, and HIV–2, largely confined          the appearance of symptoms. The slow
                                                       to West Africa. HIV is now believed to be       onset of full-blown AIDS means that
         ¥ In 2005, there were an estimated            derived from a similar virus in primates—       people may be HIV-positive yet feel
         40.3 million people living with HIV           Simian Immunodeficiency Virus (SIV)—            healthy and hence unwittingly spread the
         worldwide                                     which is thought to have ‘jumped’ into          virus to others.
         ¥There were an estimated 4.9 million          humans early in the twentieth century via          From its origins in Africa and initial
         new HIV infections in 2005                    the bushmeat trade in West Africa. This         identification in the US, HIV has spread
         ¥15—24 year olds now account for half         type of cross-species transfer is responsible   throughout the globe, with major new
         of all new HIV infections more than           for some of the most serious new infec-         epidemics occurring in Eastern Europe
         6000 become infected every day                tious diseases of recent times, including       and South-East Asia. There is currently
         ¥ By December 2005, women account-            hantavirus, Lassa fever and variant CJD.        no vaccine for HIV, though several candi-
         ed for 46% of HIV infected adults             The possibility of a similar transfer from      dates are undergoing trials, and no cure.
         worldwide, and 57% of the total in            animals to humans is the cause of the cur-         The past 25 years have seen a huge
         sub-Saharan Africa                            rent concern surrounding avian influenza.       increase in our understanding of HIV
         ¥ Of the total number of HIV infected            At that time, emerging infections were       and AIDS, with thousands of papers
         people worldwide, 95% live in the             not perceived as a threat to public health.     published on the subject each year.
         developing world                              The success of antibiotics and vaccines         However, much remains unknown, and
         ¥ By December 2004, an estimated              over the past decades had created an            the real challenge lies in converting the
         58,300 UK adults were living with HIV,        atmosphere of complacency in which the          fruits of this research into practical
         of which 19,700 (34%) were unaware            era of infectious disease—in the developed      measures for prevention and treatment
         of their infection                            world, at least—was believed to be over. In     for the millions living with this disease
         ¥ In the UK, the lifetime treatment           1969, the US Surgeon General had told           around the world.
         cost of caring for someone who is HIV         the nation that it was time to “close the
         positive is estimated to be between           book on infectious diseases”, and as            Emily Tweed is a third year Natural Scientist
         £135,000 and £181,000                         William Blattner, a researcher at NIH,                              specializing in Pathology

  06                                                                 luesci                                                          Lent 2006
   RNA genome                                Capsid
                                                                       Viruses cannot reproduce without a host cell.Although HIV can infect a vari-
                                                                       ety of human cells, it primarily infects vital components of the immune system
                                                                       such as CD4+ T-cells and macrophages. HIV infection results in a progressive
                                                                       loss of CD4+ T-cells.The rate of loss, linked to an increase in viral load, is used
                                                                       to determine the stage of infection. When enough CD4+ T-cells have been
                                                                       destroyed, the immune system becomes severely compromised, leading to the
                                                                       onset of AIDS. Most problems faced by AIDS patients are due to the failure of
                                                                       their immune systems to protect against opportunistic infections and cancers.

                                                                  Enzymes: reverse transcriptase, integrase, protease

                                                                                                                                                                          Equinox Graphics
 Viral membrane                                                Surface proteins: gp120, gp41

2. Viral Penetration After binding to CD4, gp120 undergoes a                                  1.Viral Attachment Occurs via binding of specific proteins
conformational change. This exposes gp41, as well as a previously                             (gp120 and gp41) on the viral surface to receptors on the cell
inaccessible looped region of gp120 that can bind to the chemokine
receptor.The exposed gp41 directs the fusion of the viral membrane                            surface. The cell surface receptors CD4 and a chemokine
with the host, allowing the HIV capsid to be injected into the cell.                          receptor (CXCR4) allow HIV to attach to CD4+ T-cells.

3. Uncoating
Inside the cell, the
capsid is partially
                                                                            2                                          1
dissolved to release
the viral genetic
information, RNA.

4. Reverse Trans-                                                                                                                                 8. Budding Specific
cription HIV s sin-                                                                                                                               HIV proteins inter-
gle-stranded RNA is                                                                                                                               act with the host
converted to dou-                                                                                                                                 cell membrane. The
ble-stranded DNA
                                                                   4                      5                                                       newly     assembled
(around 9000 base                                                                                                                                 capsid merges with
pairs    long)     by                                                                                                                             the host membrane
reverse transcrip-                                                                                              7                                 to form a new viral
tase, an enzyme                                                                                                                                   membrane. The HIV
common to all                                                                                                                                     particles        are
retroviruses.                                                                                 6                                                   released into circu-
Reverse transcrip-                                                                                                                                lation where they
tion is highly error                                                                                                                              can infect new
prone making muta-                                                                                                         8                      hosts. This cycle
tions, such as those                                                                                                                              results in the death
leading to drug                                                                                                                                   of the CD4+ T-cell
resistance,     likely                                                                                                                            host by an unknown
during this step.                                                                                                                                 mechanism.

5. Integration The newly synthesized HIV DNA is
                                                                        6. Protein Synthesis When the infected cell is acti-                      7. Viral Assembly
transported across the nuclear membrane into the
                                                                        vated to fight infection, the provirus instructs the                      The new viral sub-
nucleus, which stores the host genomic DNA. Inside
                                                                        host cell to synthesize the encoded HIV products.                         units are transported
the nucleus, HIV integrase directs cleavage at both
                                                                        These include RNA, which will become the genetic                          to the host cell mem-
ends of the HIV DNA and insertion into the host
                                                                        material for new viruses, reverse transcriptase, inte-                    brane for assembly
DNA.The integrated viral DNA (the provirus) now
                                                                        grase and protease, and HIV s structural components.                      into viruses.
awaits activation.

        Retrovirus: an RNA virus of the family Retroviridae, characterized by oncogenicity and the possession of reverse transcriptase.
        Chemokines: a group of small secreted proteins whose major function is to attract white blood cells to sites of inflammation.
        Macrophage: a phagocytic cell, widely distributed throughout the body, which is involved in many aspects of immune function and regulation.
        T-cell: a type of white blood cell involved in activating and directing other immune cells. CD4+ T-cells are T-cells that express the cell surface protein
        CD4 (cluster of differentiation 4).

                   In Africa...                         HIV Transmission                          ...and in the UK
              ub-Saharan Africa accounts for

                                                                                                 n November 2005, the Sunday
              25.8 million (64%) of HIV             Sexual                                       papers reported the story of a
              infections worldwide, despite         ¥ The majority of HIV infections             man miraculously cured of HIV.
        housing only 10% of the world s             occur through unprotected sexual         Andrew Stimpson had apparently
        population.                                 acts.                                    tested HIV positive in 2002, but a
           The impact of the epidemic in                                                     year later his test results were
        Africa is far different from that           ¥ The probability of transmission
                                                    varies depending on the sexual act       negative. If his story is true, it will
        found in many developed countries.                                                   be a first. But hardly any precise
        With infection rates in several             involved: 1/1000—1/10,000 for recep-
                                                    tive vaginal sex, 1/8000 for insertive   information about his case has
        countries exceeding 20%, HIV/AIDS                                                    been made public and most
        poses a serious threat to the future        vaginal sex, 1/1000 in the case of       experts are treating the case with
        security and stability of Africa. By        insertive anal sex, and 1/100—1/30       scepticism.
        crowding out other conditions, dou-         for receptive anal sex.                     The media tends to concentrate
        bling bed occupancy rates and sig-          ¥ Oral sex is not without risk;          on such extreme cases, but the real-
        nificantly increasing demand for            numerous studies have demonstrat-        ity of life with HIV is different.
        public health care services, the AIDS       ed that oral sex can result in trans-    Around two-thirds of people diag-
        epidemic has increased the burden           mission of HIV. However, the risk of     nosed with HIV in the UK are tak-
        of disease on the healthcare servic-        transmission is much lower than          ing anti-HIV medication. While
        es by up to sevenfold. Already              that from anal or vaginal sex.           more and more people are able to
        under-resourced systems, such as            ¥ Sexually transmitted infections        take just two or three pills a day,
        health, education and commerce,             (STIs) increase the risk of HIV infec-   some have to swallow as many as
        are further troubled by worker ill-         tion as they cause disruption of the     30. The dull routine of doing this at
        ness and death rates among trained          normal epithelial barriers. STIs also    precise times, day in, day out, is
        personnel. High levels of stigma            increase risk as they result in an       often accompanied by unpleasant
        impede prevention efforts and life-         accumulation of HIV-infected or          side-effects like diarrhoea, nausea
        saving antiretroviral drugs (ARVs)          HIV-susceptible cells (lymphocytes       and depression. Little wonder that
        are cost prohibitive for all but a few.                                              many people are not always able to
           As the majority of those who are         and macrophages) in semen and
                                                    vaginal secretions.                      adhere to their drug-regime. As a
        infected are in their most produc-                                                   result, the treatment is less effective
        tive years when they fall sick (aged        ¥ During sexual acts, only condoms
                                                    (both male and female) can reduce        and drug resistant HIV develops.
        20—40), their family is often left                                                      When this happens, treatment
        without any income. In two-thirds           the chances of infection with HIV.
                                                                                             needs to be switched to other
        of Zambian families in which the            ¥ Recent reports suggest that male       drugs, to which the virus is not
        father died, monthly disposable             circumcision can reduce HIV trans-       resistant. At present there are 19
        income fell by over 80%. Infected           mission. However, UNAIDS believes        licensed drugs in five different
        individuals often return home to            it is premature to recommend this        classes, with each class attacking
        die, forcing family members to give         as a preventative measure.               HIV in a different way. People with
        up work in order to provide care.                                                    HIV who have already been
        Afterwards, they must care for the          Blood or Blood Product                   through several different combina-
        children left behind. By 2010, esti-        ¥This mode of transmission is par-       tions urgently need the develop-
        mates suggest the number of                 ticularly important for intravenous      ment of new drugs.
        orphans in sub-Saharan Africa will          drug users, haemophiliacs and recip-        There are now 58,000 people
        exceed 18 million.                          ients of blood transfusions and          living with HIV in the UK this is
           There are signs of hope, however.        other blood products.                    more than ever before. A positive
        In Uganda, Zimbabwe, and Kenya,             ¥ Since October 1985, all blood          but partial explanation of this
        infection rates appear to be declin-        donations in the UK have been            unhappy reality is that, despite the
        ing. In other countries there are           screened for HIV antibodies.             disadvantages of combination
        some signs that prevention and                                                       therapy, it is extremely effective.
        political leadership are starting to        However, this is not the case in many
                                                    countries; the World Health              Indeed, since its introduction in
        break down the stigma that sur-                                                      1996, the number of deaths
        rounds the disease. Over the past           Organisation (WHO) estimates that
                                                    5—10% of HIV infections worldwide        caused by AIDS has dropped by
        few years, negotiations with phar-                                                   over 80%. Many people who began
        maceutical companies have resulted          result from transfusion of unsafe
                                                                                             combination therapy in 1996 are
        in lower costs for African countries.       blood or blood products.                 still thriving today. Nonetheless, a
        This provides perhaps the most                                                       recent Dutch study found that
        hope, as it has enabled some coun-          Mother-to-child                          men with HIV aged 25 are five
        tries to start rolling out ARVs to          ¥ In the absence of treatment, there     times more likely to die in any
        those most in need. However,                is a 15—30% risk of transmission         given year than HIV negative men
        already high infection rates, poverty,      from mother to child during preg-        of the same age.
        weak infrastructure, and impover-           nancy, labour and delivery.                 In the absence of a miracle cure,
        ished governments mean that there           ¥ Where antiretroviral drugs are         an effective response to HIV will
        is still a lot of work to be done. It       available, combined         with    a    involve ongoing scientific and
        also means that for the foreseeable         Caesarean section, the chance of         behavioural research, political
        future, HIV infection is still a death      transmission is reduced to 1%.           action, increased resources and
        sentence for most Africans.                 ¥ Breastfeeding increases the risk of    changes in attitudes.
                                  Jennifer Gibson   HIV transmission by 10—15%.                                      Roger Pebody
                  Centre of International Studies                                                            Terrence Higgins Trust

  08                                                           luesci                                                   Lent 2006
                                                                                                                                                                                                                                Fo c u s
                                                                                                            The Future’s Bright
                                                                               As a result of extensive research into          Pfizer that binds to the host cell              individual. Abstaining from ‘risky’ behav-
                                                                               HIV and AIDS over the past 25 years,            chemokine receptor is in phase II trials.       iour, or the use of condoms, are the only
                                                                               drugs have been developed that—at                  Our increasing understanding of the          ways to prevent sexual transmission.There
                                                                               least in wealthy countries—enable peo-          HIV life-cycle continues to reveal novel        are, however, a number of cultural and
                                                                               ple to survive for many years with few,         targets for the development of new classes      social constraints on these approaches.This
                                                                               if any, symptoms. This is a far cry from        of drugs. For example, Merck                    is a particular problem in developing
                                                                               the early days of the AIDS pandemic             Pharmaceuticals has started human studies       countries, where women—who account
                                                                               when it was only possible to treat the          with L-870,810, a new agent that inhibits       for 57% of adult HIV/AIDS cases in sub-
                                                                               side-effects of the disease.                    the enzyme integrase that is essential for      Saharan Africa—are often not in a position
                                                                                  Currently, anti-retroviral drugs fall into   the integration of HIV DNA into the host        to insist on ‘safe-sex’ practices (i.e.
                                                                               three main classes: (i) Nucleoside reverse      genome.Also under investigation, the inte-      monogamy and the use of condoms). To
                                                                               transcriptase inhibitors. These are non-        grase inhibitor V-165, a pyranodipyrimi-        tackle this issue, there is a large interna-
                                                                               functional ‘building blocks’ that are insert-   dine, has shown the highest anti-viral          tional effort to develop microbicides,
                                                                               ed into the newly synthesized viral DNA         activity in test-tube studies to date. The      products that, in a gel, cream, film or sup-
                                                                               and terminate its synthesis; (ii) Non-          capsid protein HIV-1, critical for matura-      pository form, could be applied topically
                                                                               nucleoside reverse transcriptase inhibitors.    tion of newly synthesized viral particles, is   to prevent HIV transmission. On 1
                                                                               Drugs which block HIV replication by            another target for drugs. Panacos               December 2005, World AIDS Day, the
                                                                               targeting the viral reverse transcriptase       Pharmaceuticals is working on the matu-         international commitment to the develop-
                                                                               enzyme, necessary for the synthesis of                                                          ment of microbicides was demonstrated by
                                                                               DNA from RNA; (iii) Protease inhibitors.                                                        announcements from four European gov-
                                                                               Drugs that block the action of the HIV
                                                                               protease enzyme, necessary for processing
                                                                               newly synthesized viral proteins.
                                                                                  One reason why HIV is so hard to treat
                                                                               is its ability to mutate its genome quickly.
                                                                                                                               “        An HIV vaccine is
                                                                                                                                        the Holy Grail of
                                                                                                                                          AIDS research
                                                                                                                                                                               ernments totaling nearly US $30 million
                                                                                                                                                                               in new funding for the International
                                                                                                                                                                               Partnership for Microbicides, including
                                                                                                                                                                               £7.5 million over three years pledged by
                                                                                                                                                                               the British government. There are five
                                                                               This is due to the high error rate of DNA
                                                                               synthesis by reverse transcriptase, estimated
                                                                               to be as high as one in every 2000–4000
                                                                               base pairs (making two to five new muta-
                                                                               tions each time the virus replicates). This
                                                                               leads to fast acquisition of drug resistance
                                                                                                                               ration inhibitor PA-457, a derivative of
                                                                                                                               betulinic acid, a cheap by-product of the
                                                                                                                               paper industry.
                                                                                                                                  However, prevention is better than cure,
                                                                                                                                                                               microbicides in large-scale efficacy trials,
                                                                                                                                                                               and many more at various stages of testing.

                                                                               and the development of a huge number of         and a vaccine against HIV remains the
                                                                               different strains of the virus. Therefore,      ‘Holy Grail’ of AIDS research. More than
                                                                               anti-retroviral drugs must be used within       100 different HIV vaccines have been
                                                                               strict treatment regimes, known as Highly       tried in animals and humans but scientists
                                                                               Active         Anti-Retroviral       Therapy    have yet to produce an effective vaccine
                                                                               (HAART), normally involving simultane-          against HIV. The rapid mutation rate of
                                                                               ous treatment with three or four drugs of       HIV makes it a formidable enemy.
                                                                               different classes, changing to new drugs as     Another difficulty for vaccine develop-
                                                                               resistance appears.Thus there is a continu-     ment is that HIV particles effectively mask
                                                                               al pressure for new anti-retroviral drugs,      their outside coat proteins so that infection
                                                                               especially those targeting additional stages    does not stimulate a strong antibody
                                                                               of the viral life-cycle.                        response. Scientists have, however, had
                                                                                  In 2003, the first anti-retroviral drug to   more success in the development of vac-         It is hoped that microbicides will be avail-
                                                                               fall outside of the three existing classes      cines that stimulate a T-cell response: the     able in five to seven years.
                                                                               became available. The drug Fuzeon               immune system attacks cells infected with          The past 25 years have seen huge
                                                                               inhibits fusion of the virus with the host      HIV rather than the virus particle itself.      changes in the prevention and treatment
                                                                               cell membrane. Structural changes on the           The leading vaccine candidate is manu-       of AIDS, particularly in the developed
                                                                               surface of the virus following binding to       factured by Merck. It uses a disabled ver-      world. Halting the pandemic, however,
Scanning electron micrographs of HIV in cultured lymphocytes by C. Goldsmith

                                                                               the host cell enable the glycoprotein gp41      sion of a common cold virus, adenovirus,        will involve continued development of
                                                                               to insert into the host membrane, causing       to carry three synthetically produced HIV       new and affordable treatments, alongside
                                                                               fusion (see page 7 for a more detailed          genes into the body (gag, pol and env).         increased prevention of infection. The
                                                                               description). Fuzeon interacts with gp41        The immune system is tricked into think-        development of a vaccine, still some
                                                                               to block the fusion process. Additional         ing that the whole virus has entered the        years in the future, is likely to be essen-
                                                                               fusion inhibitors are undergoing clinical       body and initiates an immune response.          tial if HIV and AIDS are to be eradicat-
                                                                               trials. For example, a drug produced by         Early phase II trials have given very posi-     ed completely.
                                                                                                                               tive data: over 75% of participants devel-
                                                                                                                               oped a T-cell response to HIV and the             Collette Altaparmakova is a PhD student in
                                                                                                                               level of response was similar to that seen                        the Department of Pathology
                                                                                                                               for other successful T-cell vaccines, for
                                                                                                                               example the smallpox vaccine.
                                                                                                                                  Despite some recently encouraging         
                                                                                                                               results, most scientists believe it will be    
                                                                                                                               several years before an effective HIV vac-      
                                                                                                                               cine becomes available. Along with a con-      
                                                                                                                               certed international effort to develop a    
                                                                                                                               vaccine, a number of other prevention     
                                                                                                                               strategies are also being investigated.         
                                                                                                                                  Most new HIV infections are a result of      
                                                                                                                               unprotected sex with an HIV positive

                                                                                                                         luesci                                                                       09
                Tristan Farrow introduces the computers of the future
                Energy is the source of life and all the     mined by two things: the value of the
                information contained in the universe.       input bit(s) and the type of operation
                This is because, like mass, information      performed. Computers are remarkably
                is not an abstract concept but a tangi-      simple—there are only four basic logical
                ble quantity. Einstein showed in his         operations, known as AND, NOT, OR
                famous equation, E=mc2, that mass and        and XOR, that they perform to manip-
                energy are interchangeable entities; the     ulate bits rapidly.
                same can be said for energy and infor-         The increase in speed and memory of
                mation. Energy and information are           computers over the last few decades has
                inextricably linked—an idea first            been relentless as engineers have been
                recognised in the mid-1980s by Rolf          able to pack more and more transistors
                Landauer, a researcher at IBM. It costs      onto a single microchip. However, a limit
                energy to produce information, and           on this expansion is looming, possibly 20
                energy is released when information is       years from now. As the scale of circuits
                destroyed. In the same way that mass         becomes ever smaller, the building blocks
                can be measured, information can also        no longer obey the classical macroscopic
                be measured and manipulated. Pocket          rules of physics, but start to obey a com-
                calculators, abacus machines and             pletely different set of rules—those of
                human brains do this all the time!           quantum mechanics—which govern the
                Information cannot live disembodied          microscopic world of atoms and sub-
                and so has to be encoded in a host,          atomic particles.
                physical medium; meaning that infor-           Imagine designing the smallest com-
                mation is subject to the physical laws       puter imaginable. Instead of transistors,
                governing the host object.                   we could use single atoms with two dis-

                “     A quantum computer can perform a
                       calculation in a single step where a
                      classical computer needs many more
                   The building unit of information in
                ubiquitous digital or binary computers is
                the ‘bit’.This can have two arbitrary val-
                                                             tinct energy levels to represent our bina-
                                                             ry state, a.k.a. zero or one. As in the case
                                                             of the transistor, zero could represent the
                ues, zero or one, which can represent any    atom in its non-excited or ground state,
                given physical system with two distinct      while one could represent the atom in its
                states, for example, an electric circuit     excited state. We could encode the atom
                switch.We can assign ‘zero’ when the cir-    with a zero or a one by using a well
                cuit switch is open and ‘one’ when it is     aimed laser pulse to switch the atom
                closed.The binary computer is essential-     between its ground and excited state. We
                ly a very large network of such switch-      could use this as the basic building block
                es—called transistors—that pump input        for the ultimately miniaturised computer
                strings of zeroes and ones through a         in the same way that transistors are used
                series of logical operations to produce an   in microchips.
                output string of zeroes and ones, which         There is a twist, however. Because
                represents the answer.A logical operation    atoms and other small building blocks in
                is a rule for manipulating the binary val-   nature obey the laws of quantum
                ues. Each operation takes an input of        mechanics, quantum objects, such as our
                either one or two bits, and produces a       atom, can happily exist in the ground and
                single output bit whose value is deter-      excited states at the same time. Where
                                                                                                            Jonathan Zwart

10                           luesci                                                       Lent 2006
the classical transistor could encode a sin-
gle bit, either a zero or a one, our atom
can encode both zero and one at the
same time. As unbelievable as it may
sound, if zero meant that the atom were
red and one meant that it were blue, the
                                                 “         Quantum computers are much
                                                          more than another benchmark of
consequence of the principle means that
it can be both red and blue simultaneous-                       speed and memory
ly! In the quantum world, this is known
as a ‘coherent superposition’ of two states.
The phenomena at the quantum scale are
no less real than those in the macroscop-
ic world; this qualitatively new unit of
                                                 details over the internet, say, the informa-
                                                 tion you are transmitting is jumbled by an
                                                 encryption key, known only to the recip-
                                                                                                a fraction of the time it would take the
                                                                                                most powerful classical machines.
                                                                                                   Writing new quantum algorithms is
information in which both zero and one           ient. The key is a very long number            complicated because devising these rules
coexist in a superposition is called the         obtained by multiplying two smaller            requires the invention of new logical
‘quantum bit’, or ‘qubit’ for short.             numbers, which allows the recipient to         operations that take into account the
   It becomes apparent that a system com-        reverse the jumble into useful informa-        superpositions of many states, rather than
posed of two atoms, i.e. two qubits, allows      tion. In modern cryptographic codes,           individual bits. And, since the output of a
us to encode four possible numbers (rep-         cracking the key involves factorising the      quantum computer is also a superposition
resented by zero-zero, one-one, zero-one,        very long number, i.e. decomposing it          of all the possible answers, an additional
one-zero) at the same time, compared to          into the smaller numbers that were orig-       challenge is to ensure that the ‘correct’
only two for the classical system with two       inally multiplied to obtain it. Any eaves-     answer is picked from that output.
transistors. With three qubits we have           dropper would have to be very deter-              Nobody knows what form a working
nine numbers stored simultaneously               mined to crack the code as factorising         quantum computer might take. Some
compared to three classically, with four         long numbers is an extremely hard prob-        argue that the difficulties facing pioneers
qubits we have 16 numbers and with 300           lem, even for computers.                       are so phenomenal that a working quan-
qubits we have as many numbers as there             When we multiply or divide two num-         tum machine that rivals desktops is wish-
are atoms in the universe! The memory            bers, we resort mechanically to a set of       ful     thinking. Challenges         facing
of a quantum computer increases much             rules called an algorithm. As the numbers      researchers include the preparation of
faster than that of its classical counterpart.   we are multiplying grow bigger, the time       qubits, the read-out of output qubits and
The rule is that N qubits, or atoms in the       needed to perform the operation grows          the devising of quantum algorithms. One
system, encode 2N numbers. In other              longer, but not that much longer, because      of the more intimidating problems to be
words, owing to the in-built ability to          the multiplication algorithm is efficient.     solved is how to cope with the extreme
store and process information ‘in parallel’,     The increase in difficulty is said to be       fragility of the state superposition that
a quantum computer can perform a cal-            ‘polynomial’.The problem with factoris-        form the qubits. Unless a qubit is
culation in a single step, while a classical     ing is that we know of no efficient rule       extremely well separated from interac-
computer needs many more.                        for the operation so with each extra digit     tions with the outside environment, it
   The      unusually        named      ‘Blue    added to the number being factorised,          collapses into a single state and dissipates
Mountain’ and ‘ASCI Q’ are the world’s           the time required for each operation           information in a process known as ‘deco-
two most powerful classical supercom-            increases exponentially. The problem is        herence’. As the number of qubits
puters, based at the Los Alamos                  exponentially hard. Classical computers        increases, it becomes harder to keep the
Laboratories in the United States, where         struggle with factorisation due to the         system safe from decoherence effects.
they simulate nuclear explosions. As             algorithms they use to solve it. This             These difficulties have not deterred
astounding as it may sound, a quantum            weakness is exploited by modern crypto-        enterprising researchers. A number of
computer consisting of only 13 atoms             graphic codes, which rely on the inabili-      groups around the world are already test-
could outclass Blue Mountain.                    ty of an eavesdropper to easily factorise      ing embryonic working quantum
   Quantum computers are much more               numbers over 150 digits long—a problem         devices. In 2001, Isaac Chuang and his
than yet another benchmark of speed and          that would stretch even the most power-        team at IBM successfully factorised the
memory. A more profound reason as to             ful computers and could take many              number 15 using a seven-qubit quantum
why they are a new kind of device is that        months to complete.                            computer running Shor’s quantum algo-
they are fundamentally different in the             In 1994 Peter Shor, a researcher at the     rithm. The device consisted of a liquid
way they perform logical operations.             Bell laboratories, came up with a quan-        which contained five fluorine atoms and
Classical computers use classical algo-          tum algorithm—a new set of rules—to            two carbon atoms, which were encoded
rithms—each a series of logical opera-           factorise large numbers in about the same      using radio pulses tuned by nuclear mag-
tions. For quantum computers, we would           time it would take a classical machine to      netic resonance. The scope for using the
have to devise unique quantum algo-              run simple multiplications or divisions.To     Shor algorithm for code breaking has not
rithms, which have no classical counter-         highlight the fundamental difference           gone unnoticed by governments, who
part for they would have to take account         between quantum and classical algo-            became interested and immediately
of the qubits which have the value zero          rithms, a quantum computer with atoms          increased funding. Whether or not code
and one at the same time.                        flipping state at a rate of one each sec-      breaking computers are built, however,
   Quantum algorithms may one day find           ond—an eternity by the standards of even       potential applications of quantum com-
applications in the field of code cracking.      humble desktops—could still produce an         puters are vast.Whilst classical computers
When you are sending your credit card            answer to a problem like factorisation in      struggle to predict the weather, quantum
                                                                                                machines could excel at simulating the

“       Information has to be encoded in a
           physical host, meaning that it is
                                                                                                Earth’s ecosystem, modelling the effects
                                                                                                of medicines on the human body and
                                                                                                possibly identify protein interactions.The
                                                                                                possibilities are boundless. But, for our
                                                                                                small text processing demands we should
                                                                                                probably just stick to laptops… for the
                                                                                                time being anyway.
              subject to physical laws

                                                                                                     Tristan Farrow is a PhD student at the
                                                                                                                      Cavendish Laboratory                                                     luesci                                                                     11
                                                                                                                     Recent research into DNA damage
                                                                                                                  repair pathways has lead to the develop-
                                                                                                                  ment of drugs that increase the effective-
                                                                                                                  ness of radiotherapy by further hinder-
                                                                                                                  ing DNA repair systems. Several of these
                                                                                                                  drugs have been developed by Kudos
                                                                                                                  Pharmaceuticals, who recently initiated
                                                                                                                  a phase I clinical trial in patients to
                                                                                                                  establish a safe, tolerable dose of a drug
                                                                                                                  called a PARP-inhibitor. PARP is a
                                                                                                                  DNA damage detection protein.
                                                                                                                  Therefore, inhibiting PARP using a
                                                                                                                  drug renders a major DNA repair path-
                                                                                                                  way non-functional.
                                                                                                                     “If you treat normal cells with a
                                                                                                                  PARP-inhibitor to knock out this repair
                                                                                                                  system, the cells end up with damage that
                                                                                                                  can only be repaired by one other back-
                                                                                                                  up pathway,” explains Professor Jackson.
                                                                                                                  This backup pathway involves the action
                                                                                                                  of the BRCA 1 and 2 proteins which are
                                                                                                                  commonly mutated in inherited forms
                                                                                                                  of breast cancer. Whilst a normal cell
                                                                                                                  treated with the PARP-inhibitor can
                                                                                                                  repair the damage using the BRCA
                                                                                                                  pathway, a BRCA-deficient tumour cell
                                                                                                                  cannot repair the damage and the cell
                                                                                                                  dies. In this way, the drug selectively tar-
                                                                                                                  gets BRCA 1 and 2 deficient tumour
                                                                                                                  cells and renders them more susceptible
                                                                                                                  than normal cells to the DNA damage
                                                                                                                  induced by radiotherapy.

                                DNA Damage and                                                                       Jackson adds that whilst this drug can
                                                                                                                  be used to increase the efficiency of
                                                                                                                  radiotherapy by making the tumour cells
     Equinox Graphics

                                                                                                                  less able to cope with DNA damage,

                                    Repair                                                                        researchers are finding that “the PARP
                                                                                                                  inhibitor on its own is killing the cells
                                                                                                                  without any extra damage from radio-
                                                                                                                  therapy—probably because there is a lot
                                                                                                                  of DNA damage going on in cells all the
                                 Zoe Smeaton highlights a Cambridge scientist s                                   time anyway.”
                                   efforts to revolutionize cancer treatment                                         Whilst the PARP-inhibitor can only
                                                                                                                  be used to treat cancers which are
                                                                                                                  BRCA 1 and 2 deficient, Jackson thinks
                        DNA damage, caused by external               cancer cells to DNA damage.This sensi-       that as we begin to better understand the
                        agents such as UV radiation and              tivity arises from the rapid division of     changes that occur in cancer cells,
                        smoking, or by oxygen radical by-            cancer cells in comparison to normal         molecular targeting of tumours will
                        products of intracellular metabolism,        cells, which leaves little time for DNA      become more useful: “If we can under-
                        has serious consequences if left unre-       repair to take place. Additionally, cancer   stand the differences between the can-
                        paired. Normally cells employ a host         cells often have impaired DNA repair         cerous and the normal cells, then it is my
                        of DNA repair pathways to correct            pathways making them more reliant on         belief that in the end we should be able
                        damage, but when these systems fail, a       remaining functional back up systems         to come up with drugs to specifically tar-
                        range of disorders may ensue includ-         that can also repair DNA.                    get every different kind of cancer.”
                        ing cancer, premature ageing and                This sensitivity to DNA damage is            The range of diseases potentially
                        infertility. Recent research into DNA        already exploited widely by radiotherapy     affected by impaired DNA damage
                        repair pathways in humans suggests           and most chemotherapies, which cause         repair systems is vast, providing a num-
                        that these pathways can be successful-       double-stranded breaks to form in            ber of potential applications for this area
                        ly targeted by therapeutics used to          DNA. Unlike normal cells, tumour cells       of research. For instance, studies have
                        treat several of these conditions.           cannot repair these breaks, so die in        suggested that inhibition of PARP activ-
                           According to Professor Steve Jackson,     response to treatment.                       ity—in addition to helping treat BRCA
                        who works on DNA damage and repair              Some drugs specifically target tumour     deficient cancers—could reduce heart
                        systems at the Gurdon Institute in           cells with mutations in their DNA repair     damage occurring during a heart attack
                        Cambridge: “Most people are aware of         systems. These drugs were first devel-       by up to 40%, and neuronal damage
                        the fact that exposure to too much DNA       oped by Professor Leland Hartwell—           caused by a stroke by 85–90%.The study
                        damage can lead to cancer, and for me,       winner of the 2001 Nobel Prize in            of DNA repair pathways has much to
                        research into the DNA damage and             Physiology or Medicine—and his col-          offer in the world of medicine, and it is
                        repair pathways has more to offer oncol-     league Dr Stephen Friend. Using yeast        expected that this relatively new area of
                        ogy than almost any other field.”            cells that contained genetic mutations       research will yield many effective thera-
                           Professor Jackson has set up Kudos        characteristic of specific tumours, they     pies in the future.
                        Pharmaceuticals Limited, a company           set up a drug discovery program to iden-
                        which has developed several drugs that       tify drugs and their targets that would             Zoe Smeaton is a third year Natural
                        could potentially revolutionize cancer       have practical applications in the treat-              Scientist specializing in Cell and
                        treatment by exploiting the sensitivity of   ment of tumour cells.                                             Developmental Biology

12                                                                                luesci                                                       Lent 2006
Human use of chocolate dates as far              the neurotransmitter that can produce feel-         Perhaps the best compromise is to snack
back as the Pre-classic period (900 BC           ings of ecstasy. However, tryptophan is          in moderation, particularly on dark
to AD 250). Using high performance               present in chocolate in only small quanti-       chocolate. Not only does it contain more
liquid chromatography, scientists discov-        ties fuelling debate as to whether it causes     cocoa and proportionally less sugar and fat
ered cocoa residues in Mayan ceramic             elevated production of serotonin.                than milk chocolate, but it is also full of
pots used in food preparation, dated                Phenylethylalanine, which promotes            antioxidants, called flavonoids. In fact,
around 600 BC. Numerous Mayan                    feelings of attraction, excitement, giddiness,   dark chocolate has been reported to con-
murals and ceramics are inscribed with           and apprehension, has also been isolated in      tain more flavonoids than other antioxi-
hieroglyphs depicting chocolate poured           chocolate, but again, its low concentration      dant-rich foodstuff, such as red wine.
for rulers and gods. Perhaps this is not         may be insufficient to produce the effects       Flavonoids reportedly prevent cancers,
surprising, considering that the latin           typically associated with this compound.         protect blood vessels, promote cardiac
name for the cacao tree, Theobroma                  Threobromine—a weak stimulant found           health, and counteract mild hypertension
cacao, means ‘food of the gods’.                 in chocolate—in concert with other               (high blood pressure).

 Chocolate s Chemical Charm

                                                                                                                                                   Abinand Rangesh
                                                                 Dhara Thakerar explains the science of chocolate
   When chocolate was introduced to              chemicals such as caffeine, may be respon-          Milk chocolate may not offer the same
Europe in the sixteenth century by the           sible for the characteristic ‘buzz’ experi-      benefits. In one study, patients on separate
Spanish conquistadors, a sweetened version       enced when eating chocolate. Scientists at       days ate 100 grams of dark chocolate, 100
became a luxury item throughout the con-         the Neurosciences Institute in San Diego         grams of dark chocolate with a small glass
tinent. In 1847, the first commercial            suggest that chocolate contains pharmaco-        (200 ml) of whole milk, or 200 grams of
chocolate bars were invented in England          logically active substances that produce a       milk chocolate. One hour later, those who
by Joseph Storrs Fry, with the Cadbury           cannabis-like effect on the brain, such as       ate dark chocolate alone had the highest
brothers following shortly after.                anandamide: a cannabinoid neurotransmit-         concentration of antioxidants in their
                                                 ter. Chocolate also contains N-                  blood, suggesting that the milk in milk

“       Cocoa butter may
         protect teeth by
                                                 oleoylethanolamine            and
                                                 linoleoylethanolamine. These chemicals
                                                 inhibit the breakdown of anandamide, and
                                                                                           N-     chocolate may interfere with the absorp-
                                                                                                  tion of antioxidants.

        preventing plaque
                                                 thus may prolong its effects. In addition,
                                                 elevated levels of the neurotransmitter can
                                                 intensify the sensory properties of choco-       “        Chocolate contains
                                                                                                             substances that
   Ever since, chocolate has been absorbed
into the fabric of daily life; however, few
                                                 late (texture and smell), thought to be
                                                 essential in inducing cravings.
                                                    The high fat content of most choco-
                                                 late—Cadbury’s Dairy Milk alone contains
                                                                                                          produce a cannabis-
                                                                                                        like effect on the brain
are familiar with the ways in which it
affects our body. The media’s message
about chocolate remains confusing, as
                                                 30 g of fat per 100 g—means that excesses
                                                 can contribute to obesity, which carries
                                                 with it a range of health risks, including
                                                                                                     Science can explain a number of features
                                                                                                  that contribute to the lasting popularity of
reports alternate between scrutinising           heart disease and diabetes. Nevertheless, not    chocolate, although how some of the
chocolate for health risks and praising it for   all accusations levelled at chocolate can be     effects we experience post-consumption
hidden health benefits. So, is the mantra of     justified. The often-touted link between         occur is still debatable.Whilst it is unlikely
‘eating just a piece a day’ more detrimental     chocolate and acne has been intensively          to ever be marketed as a health product,
than beneficial?                                 studied for three decades. In a 1969 study at    eating the darker varieties and snacking in
   The pleasurable feelings chocolate            the University of Pennsylvania School of         moderation could prove beneficial. But,
induces can be explained by its physical         Medicine, 65 subjects with moderate acne         one thing is certain: from perspectives both
properties. Professor John Harwood and his       ate either chocolate bars containing 10          scientific and sensory, there is nothing else
colleagues at Cardiff University believe that    times the amount of chocolate found in a         quite like chocolate.
the high stearate content of cocoa butter, a     typical bar or identical bars containing no
key ingredient in chocolate, is responsible      chocolate.Test subjects who consumed the    
for its melting behaviour and stability.         excessive amount of chocolate for four
Cocoa butter contains between 30% and            weeks did not show signs of increased acne.      Hurst,W. J. et al.,Archaeology: Cacao usage
37% stearate in its lipid content.As a result,      Additionally, chocolate has not been          by the earliest Maya Civilization, Nature
it is solid at room temperature, but when        proven to contribute to cavities or tooth        418: 289–290 (2002)
consumed, its fat content absorbs heat from      decay. Cocoa butter may in fact coat teeth
the mouth and melts at body temperature,         and help protect them by preventing              Serafini, M. et al., Plasma antioxidants from
producing the ‘melt in the mouth’ effect.        plaque formation. While the sugar in             chocolate, Nature 424: 1013 (2003)
   Chocolate has long been suspected of          chocolate contributes to cavities, it does so
aphrodisiac properties: the Aztecs thought       no more than the sugar in other sweet
it invigorated men and made women                foods. However, by altering blood flow to                     Dhara Thakerar is a second year
uninhibited. Consistent with this, the           the brain and releasing norepinephrine,                                    Natural Scientist
chemical tryptophan is found in chocolate.       some chemicals in chocolate can cause
This is used in the brain to make serotonin;     migraines.                                                     luesci                                                                                           13
All images courtesy of

                                            Are We Really Alone?
                                            Gemma Simpson explores the universe for possible signs of life

                                      From ET to the Clangers, there is no            front of the Sun (a process know as a tran-        It is possible that the planets or moons in
                                      escaping our fascination with the idea          sit). Similarly, when an exoplanet crosses in   our solar system could support some sim-
                                      that aliens exist. But after years of spec-     front of a star it will block out some of the   ple form of life. Mars has always been the
                                      ulation and searching, nobody yet has           star’s light. Using this characteristic dim-    front-runner in the search for extraterres-
                                      confirmed an extraterrestrial sighting.         ming, two projects have been planned to         trial life. In the 1970s, soil samples from
                                      This might seem like a problem when             look for habitable planets that can main-       NASA’s Viking Mars mission were found
                                      establishing a science like astrobiology,       tain liquid water. A French probe called        to contain methane. It is thought that sun-
                                      the study of life outside the Earth.            COROT is due for launch in July 2006            light would take approximately 300 years
                                         As an emerging field, astrobiology com-      and the NASA telescope, Kepler, is              to destroy methane molecules in Mars’s
                                      bines aspects of astronomy, biology and         planned for launch in June 2008.                atmosphere. Therefore, the presence of
                                      geology in the search for extraterrestrial         Even if these missions find an Earth-        methane suggests that it is being actively
                                      life. ‘Life’ could be anything from a single    like planet that has liquid water, there is     replenished, possibly by living organisms.
                                      celled amoeba to a complex organism, and        no guarantee that life will exist there.        However, other experiments failed to find
                                      it could be found within the planets and        There are certain indicators to look for        evidence of methane and the results were
                                      moons of our own solar system or on a           when detecting life on other planets. One       declared to be a false positive.
                                      distant planet orbiting another star.           such indicator is the presence of oxygen.          The Mars Express and NASA rovers
                                      Although scientists are enthusiastic about      Two space-based telescopes, NASA’s              recently found two key pieces of evidence
                                      the range of questions involved, astrobiol-                                                     that suggest life could exist on Mars.
                                      ogy is often criticised by the general scien-
                                      tific community for its speculative nature.
                                         So far, no one has come ‘face-to-face’
                                      with an alien, but there are several indirect
                                                                                      “        No one has yet
                                                                                             come face-to-face
                                                                                                                                      Firstly, there is evidence that liquid water
                                                                                                                                      could exist on or very near the surface.
                                                                                                                                      The rovers examined the mineral content
                                                                                                                                      of Martian rocks and found high concen-
                                      indications which suggest that life might               with an alien, but                      trations of sulphur and chlorine, suggesting
                                      be present elsewhere in the universe.                                                           that these minerals were repeatedly
                                      When looking at other stars, astronomers             there are several indi-                    leached out and re-deposited by water.
                                      have found planets. Encouragingly, these               rect indications to                      More convincingly, mysterious ‘spherules’
                                      exoplanets (planets outside our solar sys-                                                      (tiny spheres) were found. Spherules are
                                      tem) are proving to be quite common.                 suggest that life might                    thought to be built up layer by layer in liq-
                                      Over the past ten years, 160 exoplanets              be present elsewhere                       uid water, just like pearls in the ocean.
                                      have been found, but these planets are gas                                                      However, it remains to be discovered if
                                      giants—similar to Jupiter—making them                    in the universe                        they were created by water or if they were
                                      inhospitable. Habitable planets, like Earth,
                                      are 30 to 600 times smaller than Jupiter
                                      and therefore more difficult to detect. But
                                      there are clues that Earth-like planets do
                                                                                      Terrestrial Planet Finder and ESA’s
                                                                                      Darwin, are being designed to look for
                                                                                                                            ”         instead born in volcanic eruptions.
                                                                                                                                      Therefore, for spherules to exist, liquid
                                                                                                                                      water might once have been present on
                                                                                                                                      the surface of Mars. If water was once
                                      exist, and new technologies for finding         oxygen around other planets and moons.          present on Mars there may still be traces
                                      them are being developed.                       However, oxygen alone does not indicate         beneath the Martian surface and thus the
                                         You may remember that in 2004 Venus          life as non-biological processes can also       coexistence of life is a possibility. Secondly,
                                      could be viewed from Earth as it crossed in     produce oxygen.                                 instruments on the Mars Express orbiter
                                               combination of compounds could have             stored in some durable artefact on Earth
                                               created this red tinge. However, there have     like the pyramids.
                                               been suggestions that it could have been           It is also a possibility that Earth’s radio
                                               created by frozen bacteria such as              signals could be picked up by intelligent
                                               Deinococcus radiodurans and Sulfolobus shi-     alien life. An advanced life-form could
                                               batae which happen to be pink and brown.        potentially have picked up even the weak
                                               In 2003, sulphur traces on Europa were          early radio signals transmitted from Earth.
                                               hypothesized to be a sign of alien life.The     As we have only been transmitting radio
                                               sulphur traces look similar to the waste        waves since the early twentieth century
                                               products of bacteria that get locked into       our signals will not yet have reached more
                                               the surface ice of lakes in Antarctica.         than 100 light years away. However, with-
                                               Unfortunately, there is no way to check         in a 100 light year radius, there are many
                                               the data without a trip to Europa’s surface.    thousands of stars which could host intel-
                                                  One of the fundamental questions astro-
                                               biology aims to answer is how life began
                                               on Earth. One possible explanation for life
                                               on Earth and other planets is the inter-
                                               planetary transfer of microbes, facilitated
                                                                                               “       Recently, the Mars
                                                                                                      Express and NASA
                                               by meteorites; meteorites from Mars fre-              rovers found two key
                                               quently hit Earth. It is believed that, if
                                               there were organisms on these meteorites,               pieces of evidence
                                               they would be resilient enough to survive
                                               the harsh journey through space before
                                                                                                     that suggest life could
                                               colliding with Earth. It has been suggested                exist on Mars
                                               that Mars may have had a habitable envi-
                                               ronment before Earth.Therefore, the pos-
                                               sibility exists that we might have descend-
                                               ed from microbes that came to Earth on a
                                                                                               ligent life. Media services are increasingly
                                                                                               being delivered by technologies that do
detected methane in the atmosphere.            Martian meteorite!                              not leak radio signals. Therefore, if any
Further analysis is needed to pinpoint            In 1996, NASA scientists controversially     intelligent aliens are trying to look for us
where the methane is originating, as sub-      announced that they had found fossilised        using radio waves, they might not have
surface volcanism, rather than life, could     microbes in a lump of Martian rock              long before Earth ‘disappears’.
account for the gas.                           (ALH84001) discovered in Antarctica.               As an emerging scientific field, astrobi-
   Mars is not the only possible host for      Careful analysis revealed that the rock         ology has struggled to gain respect within
extraterrestrial life in our solar system.     contained organic molecules and tiny            the scientific community. There are con-
There is potential for life to exist on        amounts of the mineral magnetite, often         cerns that astrobiology is not distinct
Saturn’s system of rings and moons.            found in Earth bacteria. However, the evi-      enough from its parent disciplines to be a
Saturn’s moon Titan is of particular inter-    dence was insufficient to conclude that         true science. It is widely held that astrobi-
est due to its resemblance to Earth.           this was indeed a Martian fossil.               ology is too much of a speculative extrap-
NASA’s Cassini spacecraft entered orbit           The discovery of alien microbes would        olation of Earth conditions into non-
with Saturn on 30 June 2004 and imme-          be an outstanding achievement for sci-          Earth environments. A more serious criti-
diately began sending back intriguing data     ence, but what about intelligent life?          cism is that extrapolating from a single
and images. ESA’s Huygens Probe hitched        Could intelligent extraterrestrials already     data source is extremely unscientific. The
a ride on Cassini and descended into           be trying to contact us? The Search for         characterization of extraterrestrial life is
Titan’s thick atmosphere in January 2005.      Extraterrestrial Intelligence (SETI) uses       unresolved; theories as to its existence vary
On its descent to Titan, Huygens sent back     highly sensitive radio-telescopes to search     and true astrobiological experiments sim-
images of channels and gullies that looked     for broadcast messages. In 2004, the SETI       ply cannot occur at this time (with minor
very similar to the liquid-cut features seen   project received a puzzling radio signal        exceptions such as the ALH84001 mete-
on Earth. However, the liquid observed is      three times from the same region of space.      orite found in Antarctica).
most likely to have been liquid methane        This signal is widely thought to be the best       Even if civilisations are common in the
and not water. Furthermore, two teams of       candidate yet for alien contact; the catch      galaxy then you hit the Fermi Paradox that
astronomers found short-lived clouds of        being that it came from a region in space       can be summarised as:‘The belief that the
methane on Titan which lasted between          where there are no obvious stars or plan-       universe has many advanced civilizations,
several hours and a day. Whether or not        ets. It may be that the signal is simply from   combined with our observations that sug-
these clouds of methane were produced by       a yet unknown physical phenomenon.              gest otherwise, is paradoxical, suggesting
microbes is unclear. Huygens also revealed        If aliens are trying to establish contact,   that either our understanding or our
a possible ice volcano on Titan so geolog-     they will probably be using a method            observations are flawed or incomplete.’ So,
ical activity could have produced the          more sophisticated than radio waves.            where are they? Have they already arrived
methane clouds.                                Lasers are a possibility as they hold more      on Earth and we just don’t know about it?
   Other signs of life have been observed      information than a radio wave and are           Would they prefer not to communicate
within Venus’ clouds and on the icy surface    less prone to interference allowing a bet-      with us? Or, are we simply missing their
of Jupiter’s moon Europa. Data from the        ter quality signal to travel longer dis-        signals? It could be that intelligent life has
Venus probes and landers gave ‘chemical        tances. Optical SETI is another branch of       yet to form in the universe. Maybe we
hints’ that microbes could exist in the        the search for alien life.They use ground-      really are alone.
clouds above Venus. In addition, a red tinge   based telescopes to look for alien laser
was observed on the surface of Europa. No      signals hitting Earth. Maybe an alien mes-          Gemma Simpson is a PhD student in the
one has yet been able to explain what          sage is staring us straight in the face,                            Cavendish Laboratory
     Ben Lambert
                   Probiotics: More Pros than Cons?

                                          Louise Woodley on the benefits of ingesting live bio-cultures
                   Who would have imagined 50 years              antimicrobial compounds—short pep-            108 cells of Lactobacilllus reuteri or a
                   ago that people would be willingly            tides termed bacteriocins.                    placebo in liquid form over a total of 80
                   and deliberately consuming products              There is no published data to show         days.This was a double blind trial, where
                   containing bacteria? Yet in recent            that probiotics are able to replace the       neither the worker nor the administrator
                   years foodstuffs containing ‘friendly         body’s natural flora, only evidence that      of the drink knew whether the dose
                   bacteria’ or probiotics such as yoghurt       they form beneficial temporary colonies,      contained bacteria or not. Of the day-
                   drinks have become widely available.          which may perform the same function as        time workers in this trial, 23 of 87 in the
                   Countries such as Finland and                 the natural commensals. Thus, probiotic       placebo group took sick leave compared
                   Sweden have been actively using pro-          strains are never long-lived inside the       to 10 of 94 in the L. reuteri group, statis-
                   biotic products for several decades.          body. On the plus side, there is now an       tically significant but not very impressive.
                   However, many scientists remain scep-         increasing body of evidence to show that      By contrast, of the shift-workers studied,
                   tical about their benefits. So what           probiotics do have real benefits in treat-    33% of the placebo group took sick leave
                   exactly does the scientific literature        ing or preventing certain diseases. These     compared to none of the workers taking
                   tell us about the real effects of these       range from general claims such as a           the active supplement. This suggests that
                   substances?                                   reduction in sick-days taken by adults or     probiotics have a noticeable effect in
                                                                                                               those who already have weakened
                                                                                                               immune systems. Importantly, both

                    “onProbiotics have a beneficial effect
                        those who already have weakened
                                                                                                               groups had been matched demographi-
                                                                                                               cally: there were comparable numbers of
                                                                                                               males and females in each group and the
                                                                                                               mean age for both groups was the same.
                                              immune systems                                                   These new data are entirely in agreement
                                                                                                               with another Swedish study using the

                      The current theory is that by ingesting
                   up to one billion cells of ‘good bacteria’,
                                                                 illnesses contracted by infants in day-care
                                                                 centres, to specific examples of preven-
                                                                                                               same bacteria in nursery children, where
                                                                                                               there was a 70% reduction in absences in
                                                                                                               children taking the bacterial supplements
                                                                                                               compared to those who took a placebo.
                   such as Lactobacillus acidophilus or          tion of diarrhoea whilst taking antibi-          Despite an increasing number of
                   Bifidobacterium bifidum, every day, the       otics, and reductions in the recurrence of    papers, such as those discussed above,
                   intestine is colonised where naturally        yeast vaginal infections and irritable        there still remain many who are scepti-
                   occurring beneficial, or commensal, bac-      bowel syndrome. What is more, taking          cal about probiotics. One of the argu-
                   teria have been eliminated. This can          probiotics has no known side-effects,         ments against purchasing probiotic
                   occur through stress, taking antibiotics or   including a negligible risk that the          products is that in the US, beneficial
                   oral contraceptives, or following a severe    friendly bacteria could enter the blood       bacteria are considered to be a food sup-
                   bout of diarrhoea. By adhering to the         stream and cause infection.                   plement and not a pharmaceutical. This
                   intestinal wall, these good bacteria pre-        One of the most recent studies to be       means that they do not have to be passed
                   vent harmful bacteria from attaching to       published on the benefits of probiotics       by the Food and Drug Administration
                   and over-colonising the gut, and thus         involved a study of 181 factory workers       (FDA), a key indicator of a product’s
                   maintain what is commonly referred to         in Sweden. Shift-workers are recognised       safety and clinical efficacy. This legally
                   in advertisements as “a healthy intestinal    to be at greater risk than day-time work-     prevents a manufacturer from making
                   flora”. The antimicrobial properties of       ers of contracting short-term illnesses,      clinical claims about the benefits of a
                   probiotics are thought, in a large part, to   such as gastroenteritis or the common         product in the treatment of any given
                   be due to their reinforcement of the bar-     cold, and days off due to these causes can    medical condition. Another downside,
                   rier function of the intestinal mucosa. In    cost up to 2.2 billion euro per year in       due to the supplement status of probi-
                   addition, some probiotics, such as            Sweden alone. In this study, each factory     otics, is that the production and testing
                   Lactobacillus plantarum strains, secrete      worker was given a daily dose of either       of probiotic foods is not strictly regulat-

16                                                                             luesci                                                       Lent 2006
ed. What the manufacturer claims to be          already indicated that some strains of bifi-      There is now increasing data to back
providing you on the outside of the             dobacteria can survive low pH better           up claims that probiotics can be benefi-
packet may not strictly correspond to           than others.This is likely to be an intrin-    cial for a range of health conditions,
what is inside. A study conducted in            sic characteristic of different strains of     especially in the young or immuno-
Belgium on 55 different products specif-        bacteria, and so is a simple way to rule       compromised. However, there is a lack of
ically sold as probiotics found that only       out inappropriate sources of probiotics.       mechanistic data to explain exactly how
13% of the products actually contained          Another important factor is that probiot-      probiotics act or whether certain bacte-
the bacteria listed on their labels, with       ic bacteria should adhere to the mucosal       ria may be more useful for preventing
more than a third containing no live            lining of the gut, as this has been corre-     one illness than another—so not all pro-
bacteria at all!                                lated with reducing the duration of diar-      biotics may be as effective as each other.
  Some of the advice that has been
offered is to purchase products made by
reputable pharmaceutical firms or food
companies, and to buy products that have
a sell by date as far off as possible.This is
                                                 “           The production and testing of
                                                                probiotic foods is not
because bacteria have a shelf-life, and the
longer they are kept in a shop, the lower
the count of viable bacteria in the prod-                          strictly regulated
uct at the time of consumption.
  Another argument against probiotics is
that the low pH of stomach acid may
wipe out most bacteria as they travel
                                                rhoea. This can also be tested in the lab
                                                using cultures of intestinal cells as model
                                                                                               The consumer needs to be aware of what
                                                                                               they are purchasing; it is probably wise to
through the stomach and small intestine,        systems, although there is not currently       buy products that are more likely to have
and so prevent them from colonising the         one recommended cell line in use, as           been tested and standardised, and prefer-
intestine. In an effort to respond to these     there have been differing results.             ably those that have been trialled in stud-
arguments and several others, it has been       Worryingly, observations have also been        ies with positive outcomes.
proposed that probiotics should pass a          made that culturing the same strain of
number of laboratory-based tests to             bacteria over a long period of time in an
establish their stability and efficacy.These    industrial environment may change its              Louise Woodley is a PhD student in the
include tests for acid stability, which have    adhesion properties.                                          Department of Biochemistry


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                                                                        The Sixth Sense
                                                         Juliette McGregor uncovers the artwork we never knew
                                                                    we could see, Haidinger s brush
                                                      individual differences, like the thickness of
                                           Bees do    the cornea.
                            it, fish do it and even      To see Haidinger’s brush, view a bright-
                           plants do it, but few      ly illuminated white sheet of paper
                          are aware that humans       through a piece of Polaroid or the lens of a
                      can do it too: detect the       pair of polarized sunglasses. If you are hav-
          linear polarization of light with the       ing difficulty, try quickly rotating the
         naked eye. Surprisingly, our ‘sixth          Polaroid through a right angle.The image
       sense’ remains relatively obscure              is easier to observe if it is moving because
     despite the abundance of sources of par-         the change in polarization direction rein-
     tially polarized light around us, ranging        forces the new brush with the afterimage
     from the clear blue sky above to the liq-        of the previous one. If you have a mobile          Figure 1. Haidinger s brush
     uid crystal displays (LCD) of laptops            phone, you can use its LCD to see polar-
     below.The difficulty of visualizing polar-       ized light. Firstly, adjust the phone to dis-     carotenoid pigments are associated with this
     ization and an incomplete understanding          play a blank white screen, and then rotate        fibre framework, and this structure is
     of its physical mechanism have con-              it quickly by 90°. The LCD of a laptop            responsible for the phenomenon.
     tributed to the general lack of informa-         would also work.                                     Haidinger’s brush is believed to result
     tion regarding the phenomenon. But                  Once you have learned how to recognise         from two distinct features of these fibres.
     with a few tips and practice, you too will       Haidinger’s brush, you should be able to see      Firstly, they are dichroic elements, so a
     soon be able to see and understand the           it even when looking at a stationary              change in the polarization angle produces a
     polarization of light.                           Polaroid.After a few seconds, the image will      change in their transmission of light. In this
        Most often called Haidinger’s brush, the      fade as your brain adapts and the eye             case, more light is absorbed if the polariza-
     image was first reported in 1844 by the          fatigues, but it is visible long enough to        tion direction is perpendicular to the fibres.
     Austrian mineralogist Wilhelm Haidinger.         catch a glimpse.With enough practice, you         Secondly, their arrangement in a radial or
     Since then, numerous literary and scientific                                                       concentric pattern is thought to influence
     figures including Leo Tolstoy and Hermann
     von Helmholtz have been impressed by the
     visualization. Scottish physicist James Clerk
     Maxwell situated the origins of the image
                                                      “       Our sixth sense is
                                                             obscure despite the
                                                                                                        light transmission by preventing absorption
                                                                                                        from averaging out.
                                                                                                           White light depleted of blue appears yel-
                                                                                                        low, accounting for the yellow bowtie
     in the structures of the eye by describing it              abundance of                            shape that appears perpendicular to the
     as, “something subjective, as it moves with                                                        plane of polarization.The blue regions are
     the eyeball.” He was right; as an entoptic                polarized light                          believed to be psychological in origin, pro-
     phenomenon, Haidinger’s brush is due in                      around us                             duced as a contrast effect in response to the
     part to a small glitch in the dichroic nature
     of certain eye pigments, particularly lutein.
     Nevertheless, it is a physical effect that
     results from the interaction of polarized
                                                      can observe Haidinger’s brush in the sky by
                                                      slowly roving about its zenith after sunset
                                                                                                        physical yellow.
                                                                                                           Clinical studies of Haidinger’s brush have
                                                                                                        proven difficult and the exact theory
                                                                                                        behind the visualization is yet to be veri-
     light with the symmetrical, optically active     on a clear day and tilting your head from         fied. Recently, mathematical models of the
     elements of the retina.                          side to side in the direction of the gaze.        eye’s optically active elements have been
        What does Haidinger’s brush look like?           Explaining Haidinger’s brush requires an       used to generate computer simulations
     The image has been described as resem-           understanding of how polarized light inter-       mimicking the observed behaviour. These
     bling a bow tie, hourglass, butterfly or         acts with the retina, a complex and unusual       studies may make Haidinger’s brush useful
     brush (a mistranslation of the German            structure in the eye. Before reaching the         as a medical diagnostic tool. Currently, the
     ‘Büschel’ meaning ‘tuft’ or ‘stook’). To the     photoreceptors, light is scattered as it passes   ability to see the image is used to diagnose
     trained eye, polarized light looks like a dis-   through several neuronal layers. In the           various disorders of the eye, especially reti-
     tant elongated yellow stain, pinched at the      fovea—a region specialized for high acuity        nal damage. Problems visualizing
     centre with yellow streaks subtending sev-       vision—this scattering is reduced by sweep-       Haidinger’s brushes may be an early indica-
     eral degrees around a fixation point rough-      ing neurons and other structural elements         tor of eye disease, particularly age-related
     ly the size of your thumb at arm’s length        radially outwards such that the light rays fall   macular degeneration, the leading cause of
     (Figure 1).The image is flanked by shorter       unimpeded onto the rod and cone cells.            blindness in the United Kingdom.
     bluish-purple regions that cross the yellow      The displaced neuronal fibres form a radi-
     arms at 90°. The appearance of the brush         ally symmetric region known as the macu-               Juliette McGregor is a fourth year Natural
     varies from person to person because of          la lutea or ‘yellow spot’. Blue absorbing                         Scientist specializing in Physics

                                                 Weak blue absorbtion
                                                 parallel to fibres
       Incident                                  Strong blue absorbtion
                                                                                                                                                            All images by Juliette McGregor

      Vertically                                 perpendicular to fibres
           light                                 Figure 2.When exposed to
                                                 vertically polarized white
                                                 light, the fibre arrangement
                                                 favours blue absorption
                                                 along horizontal meridian      Figure 3. The blue absorbing pigment molecules may be arranged
                                                 such that a yellow brush is    radially or concentrically on the fibre framework, in either case the
                            Macula lutea         perceived as shown.            explanation holds.

18                                                                   luesci                                                             Lent 2006
           Citrus Paradisi

                                                                                                                                                   Sasha Krol
                                                                                 Chi Ngai Chan examines the link
                                                                                between grapefruit juice and Viagra
To most people, grapefruit juice is a nat-       grapefruit juice to mask the taste of ethanol   Initial evidence suggests that drinking
ural product that supermarkets sell by           in an investigation examining ethanol’s         grapefruit juice can increase the blood con-
the litre and people consume daily with          effects on the drug felodipine (an antihy-      centration of sildenafil citrate after it is
their breakfast. However, research has           pertensive agent). In this study, the blood     administered due to the inhibition of
shown that grapefruit juice can interact         concentrations of felodipine were much          CYP3A4. Current research implies that the
with mechanisms used by the human                higher than those observed previously.          increase is unlikely to potentiate either the
body to eliminate foreign chemicals.             Analysis of the possible causes of the high     therapeutic or adverse effects of sildenafil
Consequently, this can affect the way the        felodipine levels found that grapefruit juice   citrate. On the other hand, considering that
body deals with drugs such as Viagra, a                                                          certain side effects of sidenafil citrate, such
drug prescribed for erectile dysfunction,
and terfenadine, an anti-histamine used
to combat hay fever.
   Our bodies are capable of metabolising
                                                 “       Drinking grapefruit
                                                       juice can increase the
                                                        blood concentration
                                                                                                 as hypotension (a decrease in blood pres-
                                                                                                 sure) may become more prominent, espe-
                                                                                                 cially if being used concurrently with an
                                                                                                 antihypertensive agent, avoiding grapefruit
foreign chemicals: a natural defence mech-                                                       juice would be a sensible precaution.
anism developed to detoxify substances                   of sildenafil citrate                      The effects of grapefruit juice can be
such as toxins in poisonous plants. When                                                         extremely serious, a scenario best illustrated
you take a drug it does not stay in your sys-             (Viagra) after it is                   by the tale of the antihistamine drug terfe-
tem forever. Any substance that the body                                                         nadine. Histamine is an important mediator
views as ‘alien’ (such as a drug) can be
removed from the body through a variety
of biochemical reactions, that convert the
drug into more hydrophilic products,
                                                 was the culprit, it was affecting the way in
                                                 which felodipine was metabolised in the
                                                                                                 in allergic reactions, causing symptoms such
                                                                                                 as itchiness and reddening of the skin, con-
                                                                                                 ditions familiar to hay fever sufferers.
                                                                                                 Antihistamines, like terfenadine, block the
which are then excreted in urine. These          body! It is now known that certain con-         receptors for histamine, thereby preventing
reactions are divided into phase I and phase     stituents of grapefruit juice inhibit enzymes   its effects and relieving allergic symptoms.
II, the former generally involving the           involved in phase I reactions. These               The problem is that terfenadine is a pro-
                         break-up of the         enzymes are part of a large family called       drug and must be metabolised to the active
                                   drug mol-     cytochrome P450. The mechanism by               product, fexofenadine, by P450. However,
                                                 which they work involves a complex cycle        when P450 is inhibited, terfenadine builds
                                                 of reactions called the monooxygenase           up in the body and interacts with a potassi-
                                                 P450 cycle. Interfering with this metabolic     um channel in the heart encoded by the
                                                  process, as grapefruit juice does, has been    HERG gene.This can disrupt normal func-
                                                      shown to have major effects upon the       tioning of the heart resulting in cardiac
                                                        action of certain drugs in the body.     arrhythmia. Unfortunately, deaths occurred
                                                                  The      most     important    before this serious side-effect was discov-
                                                                          inhibitory compo-      ered. In 1998 terfenadine was withdrawn
                                                                              nent in grape-     from the market in the US and Canada
                                                                                   fruit juice   although it still remains on sale in the UK
                                                                                                 (but only on prescription).Terfenadine has
                                                                                                 now been largely replaced by the active
                                                                                                 compound, fexofenadine, thus sidestepping
                                                                                                 the P450 pathway.
                                                                                                    The story of grapefruit juice and drug
                                                                                                 interaction is by no means over.There are
                                                                                                 still many unknowns, and compounds in
                                                                                                 the juice may well affect more than just the
                                                                                                 P450 pathways. Interestingly, other fruit
ecule, for       example                                                                         juices such as cranberry juice have been
hydrolysis or deamination,                                                                       shown to have similar effects, but grapefruit
while phase II reactions nor-                                                                    juice is certainly one of the better charac-
mally involve addition of chemical                                                               terized. So, next time you drink a glass of
groups to the phase I derivative. Not all                                                        grapefruit juice take a minute to think
drugs are metabolised; some, such as the                                       has been iden-    about the chemicals contained within, and
antibiotic gentamicin, can be excreted           tified as 6’,7’-dihydroxybergamottin which      the startling effects they can have upon
from the body chemically unchanged.              inhibits an isoenzyme of P450: CYP3A4. It       your body!
Incredibly, drug metabolism can activate         has been suggested that 6’,7’-dihydroxy-
drugs converting them from their inactive        bergamottin may also decreases the expres-                    Chi Ngai Chan is a second year
state, known as a pro-drug, to the active        sion of CYP3A4. If there are fewer enzyme                                  Natural Scientist
form of the drug.An example of this is the       molecules present, the rate at which a drug
pro-drug enalapril which only inhibits its       is broken down will decrease, resulting in
target once hydrolysed to enalaprilat, an        higher blood concentrations of that drug.        Under normal circumstances, grapefruit
antihypertensive agent (a drug which low-           One drug metabolised by CYP3A4 is             juice does not harm the body. However,
ers blood pressure).                             Viagra (sildenafil citrate) which is broken      you should discuss possible drug interac-
   So where does grapefruit juice fit into all   down to desmethyl sildenafil, a compound         tions with your doctor or pharmacist.
of this? About 15 years ago a study used         that is pharmacologically much less potent.                                                     luesci                                                                                      19
On the Cover
                                          Small Fields of View
                           Victoria Leung interviews Ed Simpson, the scientist behind our cover image

               The Department of Materials Science                                                                            each other through the fields they
               and Metallurgy’s High-Resolution                                                                               induce. The field lines are digitally over-
               Electron Microscopy (HREM) group                                                                               laid, as are the colours which have been
               occupies a section of the old                                                                                  determined from the direction and
               Cavendish Laboratory on Free School                                                                            intensity of the magnetic field.
               Lane. Inside, in what was once the                                                                                One of Simpson’s smaller projects
               physicist James Clerk Maxwell’s clock                                                                          includes the iron-carrying protein, fer-
               room, PhD student Ed Simpson uses a                                                                            ritin. The iron carried by this protein in
               Transmission Electron Microscope                                                                               most of its forms is not magnetic.
               (TEM) to perform electron hologra-                                                                             Simpson is investigating the iron in peo-
               phy, a technique that images magnetic                                                                          ple with the condition haemochromato-
               and electrostatic fields. Using this                                                                           sis in which too much iron is produced.

                                                                                                            Abinand Rangesh
               technique, Simpson studies a surpris-                                                                          Another project is the characterization of
               ing diversity of nanomagnetic systems,                                                                         damaged brain cells in Alzheimer’s
               which he does in collaboration with                                                                            patients. This disease is thought to be
               colleagues from Europe and the US.                                                                             associated with an increase in iron in the
                  Electron holography, a TEM imaging                                                                          brain. Simpson examines amyloid
               technique that can measure the magni-         of these chains. The magnetic moment                             plaques from the brains of sufferers to
               tude and direction of magnetic fields, was    produced by such a chain is directly pro-                        determine if they contain iron in a dif-
               first proposed in the 1940s and has been      portional to its length, and it is found                         ferent form. In studies of complex
               greatly developed since the 1970s. The        that the bacterium will grow a chain to                          microstructures such as cells and pro-
               Aharonov-Bohm effect—when an elec-            the particular length that optimises its                         teins, electron tomography images are
               tron passes through a region of non-zero      magnetic moment.                                                 often usefully compared with electron
               magnetic potential, the quantum                  He also works with a group at Bremen                          holograms, to combine three-dimen-
               mechanical phase of the electron is           University, who focus on the genetic                             sional visualization of the physical struc-
               altered—forms the underlying principle        control of the chain growth.Their genet-                         ture with the magnetic structure.
               of this technique. The important point        ic engineering experiments have pro-                                In his current work, Simpson uses the
               about electron holography is that it          duced bacteria with different morpholo-                          apparatus at its very limits. Over the past
                                                             gies of the chains, including two-dimen-                         six years, the HREM group has devel-
                                                             sional arrays of the magnetic crystals.                          oped electron holography to a new level

               “      Electron holography
                     measures the magni-
                                                             Simpson has found that the crystals in
                                                             the arrays interact magnetically with
                                                             each other in much more complex ways
                                                                                                                              of spatial (approximately 10 nanometres)
                                                                                                                              and magnetic (approximately millitesla)
                                                                                                                              resolution. Alongside his contribution to
                     tude and direction of                   than the linear chains. These small scale                        various fields of research, Simpson is
                                                             biosystems are important models that                             working to further increase the micro-
                         magnetic fields                     show how the magnetic interactions of                            scope’s resolution and the sophistication

               allows not only the amplitude of an elec-
               tron to be measured as in other electron
                                                             particles can be co-ordinated. The study
                                                             of these systems also has applications for
                                                             magnetic recording. In this industry,
                                                             information density has reached a limit
                                                                                                                              of its quantitative processing.

                                                                                                                                    Victoria Leung is a third year Natural
                                                                                                                                           Scientist specializing in Physics
               microscopes, but also the electron’s          due to the fact that the more a crystal is
               phase. In a specialised TEM, a highly         reduced in size, the more likely it is to be
               coherent source of electrons creates an       superparamagnetic (having no stable
               electron beam that is split in two by a bi-   magnetic moment). Embedding the par-
               prism. When the two beams are recom-          ticles in a matrix as in other natural sys-
               bined, the resulting interference pattern     tems, such as in rocks, allows magnetic
               is dependent on their relative phases,        properties at a much smaller volume.
               which can thus be measured from the              The cover image is taken from
               interference pattern with high accuracy.      Simpson’s work with the Department of
               Electron holography was one of the first      Engineering at Cambridge. The depart-
               ways of verifying the physical reality of     ment grows nanotubes using a
               the magnetic vector potential. Only now,      cobalt/palladium catalyst for a variety of
               achieved by a handful of groups in the        purposes. Incidentally the catalyst, which
               world including HREM at Cambridge,            is embedded in the end of the tube, is
               can magnetic fields be resolved down to       magnetic. Simpson characterises the
                                                                                                                                                                               Ed Simpson

               nanometre length scales.                      magnetic properties of the tubes. These
                  Currently Simpson focuses mainly on        tubes may form the building blocks of
               examining magnetotactic bacteria, work-       future hi-tech components: the magnet-
               ing with, among others, a research group      ic particles at the end of the tube will                          Magnetite Crystals. Induction map of the
               in Hungary.These fairly common bacte-         affect the spin of an electron that is                            magnetic field of two double chains of mag-
               ria grow magnetite crystals along chains      passed through the tube, a phenomenon                             netite nanocrystals taken from magnetotac-
               in their bodies which they use to navi-       that can be applied in spintronics, a                             tic bacterium.The map was created from an
               gate in the geomagnetic field, for exam-      branch of electronics in which the spin                           electron hologram in the TEM, and colours
               ple to move up and down a water col-          property of electrons is exploited for                            are derived from the direction and intensity
               umn while seeking a feeding site.             information storage. The cover shows                              of the field, with field lines overlaid. Each
               Simpson      studies     the     magnetic     two of the nanotubes with magnetic                                crystal is approximately 50—70 nm.
               microstructure and magnetic interaction       crystals at their ends interacting with

     20                                                                    luesci                                                                            Lent 2006
                                                                                                                                                            A D ay i n t h e L i f e o f …
A Defence Scientist
Louise Woodley speaks to Jezz Ide about his work at QinetiQ
In recent years, national security and
defence have received increasing
attention, both in government agen-
das and in the media. Although little
publicised, there is much ongoing
research into new technologies that
aim to exploit cutting-edge science
to protect the country’s people and
their businesses.
   Jezz Ide works for QinetiQ, a world-
leading defence technology and security
company, employing a staff of over 9000
at several dozen locations across the UK.
QinetiQ was formed in 2001 when the

Ministry of Defence’s Defence
Evaluation and Research Agency (MoD
DERA) transitioned to the private sec-         of skills covering electromagnetic pre-          Have you ever had any ethical concerns
tor. The Public Private Partnership            diction and measurement, including               about projects you have been asked to work
arrangement that exists at the company         physics, chemistry, and mechanics.A typ-         on? Are employees able to decline working
today allows QinetiQ access to over 50         ical day can include discussions with            on specific projects?
years of technological experience in           customers on current or future work,                The advantage of working for a large
projects from liquid crystal displays to       planning the development of new com-             organisation with broad research interests
advanced robotics.                             puter codes that will predict the interac-       is that people can generally be matched
                                               tions of electromagnetic fields and solid        to an area in harmony with their beliefs.
When did you begin working at QinetiQ          bodies such as planes and tanks more             If you are a specialist in a particularly lim-
and how did you get the job?                   efficiently, and designing more cost-            ited field, this may be more difficult.
  I first began working for the Royal          effective ways of validating computer            However, many areas can have civilian
Radar Establishment (RRE) in 1974. It          predictions using physical models. In the        applications, for example, in Stealth
went through numerous transitions to           same day I can, therefore, alternate             understanding how radar interacts with
become DERA and finally QinetiQ.               between thinking or staring at a com-            turbine blades can be used to predict the
Each transition was marked by a merger         puter screen and mediating or con-               effect of a wind farm on airport radar.
of several locations and a broadening of       tributing to meetings.
expertise and responsibilities.                                                                 Due to the confidential nature of the
  Having read Electrical and Electronic        Having worked at QinetiQ as it made the          research, do you get much opportunity to
Engineering at UMIST, I had a post-uni-        transition from a government body to a           discuss ideas with other scientists from other
versity job painting everything white for      commercial venture, has the nature of your       institutions or companies?
the Army on Salisbury plain (simple            work changed significantly?                         The MoD generally prefers to place
instructions—if it moves, salute it; if not,      The nature of the work has changed            large projects with consortia rather than
paint it) when a friend at RRE said            more in response to the changing nature          individual companies. They hope to
“Come and work here—all I do is walk           of the MoD, our part-owner and major             achieve a mix of skills from the
up and down a runway, swinging my              customer. Since the Strategic Defence            unchained thoughts of academia to the
arms and pretending to be a man. Even          Review and the introduction of Smart             ‘oil and sawdust’ of manufacture. In these
you could do that!” He was being a tar-        Procurement (a procedure aimed at mas-           circumstances it is necessary to commu-
get for portable radar to train operators to   sively reducing the delays in major pro-         nicate with your partners just enough to
distinguish between different activities,      grammes) the emphasis has changed                ensure the success of the project, but not
such as marching or sneaking around,           from the delivery of research to the             so much that they could succeed without
using the different swishing noises pro-       delivery of capability. For QinetiQ,             you.This is made more difficult by shift-
duced by the radar. Naturally, I applied       which started as a research organisation         ing alliances, where a collaborator for one
for a similar job but was posted to the        rather than a manufacturer, the challenge        project may be a competitor on another.
Metrology (the study of systems of meas-       has been to convert technical expertise
urement) Department instead.                   into commercial products.                        What is the best aspect of your job?
                                                                                                   The technological challenges never go
Did you have any previous experience in        Are there any projects that you have been        away: there is always faster, bigger, better
the field?                                     involved in that stand out in your memory        to aim for.What is more, there is a bene-
   No. I had done work experience as a         as being particularly interesting or exciting?   ficial spiral whereby improvements in
dustman and was looking for anything              The most interesting project I have           prediction capability are confirmed by
that did not involve rotten banana skins       been involved in from the personal view-         measurements, leading to a better under-
sliding down my neck! My current job           point was an International Comparison            standing of some interactions, which the
title is RF Stealth Expert Group Leader,       of Microwave Power. This gave me a               leads to an improvement in the predic-
and this combines my previous experi-          technical and intellectual challenge and         tion capability, and so on.
ence as a metrologist, working on              enabled me to interact with international
Microwave National Standards for the           peers. Metrology and standards underpin          What is the worst aspect of your job?
National Physical Laboratory, with elec-       all trade but are largely taken for granted;       People assuming that because I’m an
tromagnetic experience I gained from           the drivers for many technical improve-          expert in microwaves, I can fix their
the Radar Department.                          ments in metrology come from trade dis-          kitchen appliances.
                                               putes, as how big you want a gallon of
What does your typical work day involve?       petrol to be depends on whether you are               Louise Woodley is a PhD student in the
 The team that I lead has a wide range         buying or selling.                                               Department of Biochemistry                                                   luesci                                                                                   21
Away from the Bench
                                                      Volcanic Chemistry
                                                    Rob Martin investigates what Mount Etna has to offer
                      Having spent the first year of my PhD
                      computer modelling the chemistry of
                      volcanic plumes, I felt I knew quite a
                      bit about volcanoes. I’d read that
                      active volcanoes, such as Mount Etna
                      in Sicily, continuously pump out gases
                      into the atmosphere, including H2O,
                      SO2, CO2, H2S, CO, HCl and HF,
                      along with a cocktail of minor com-
                      ponents. I had modelled what happens
                      as these gases cool, what happens as
                      they dilute, and even what happens
                      when they start to mix with atmos-
                      pheric oxygen. But something was
                      missing in all of this…
                         In September 2005 I flew to Sicily
                      with a group of Cambridge volcanolo-

                                                                                                                                                               All images by Rob Martin
                      gists to meet with our collaborators from
                      the Universities of Palermo, Heidelberg
                      and Birmingham, the Woods Hole
                      Oceanographic Institute, and the Istituto
                      Nazionale di Geofisica e Vulcanologia in
                      Italy. The aim was to spend a week sam-
                      pling the gases and particles released
                      from open vents on the summit of Etna,        Rob Martin on the slopes of Mount Etna
                      which is currently about 3330 metres
                      above sea level—the summit height            over the edge of the crater, it became        made our way back down to the B&B.
                      varies, but fortunately it didn’t during     evident that on one side of us was a gap-     That evening the instruments were pre-
                      our stay! From our base camp at a            ing volcanic vent pouring out hot gases,      pared for the following day, and the sam-
                      Sicilian B&B, Etna was clearly visible,      while on the other was a large fall down      ples were safely stored for analysis back
                      with its plume of volcanic gas drifting      the side of the mountain! Most of the         in the UK. Such was our routine for the
                      away to sea.                                 time the gases emerging through the           rest of the week. The data we collected
                         The trip to the summit involved a         vent on the crater floor obscured the         will be used to further our understand-
                      sturdy-looking 4x4, and roads that           bottom, but every now and then the            ing of the chemistry of volcanic plumes,
                      quickly became dirt tracks as the scenery    wind cleared the gases from the crater,       and probe the mechanisms by which vol-
                      changed from forests to impressive lava-     revealing the vent itself.                    canic aerosols form and grow as the vol-
                      flows carpeting the landscape. There was        Fear of death aside, I set about doing     canic plume cools.
                      no ‘are we nearly there yet?’ about this     some science. Acidic gases (HCl, HF,
                      particular journey. For the final push we    H2SO4) were collected on alkali-soaked
                      had to leave the 4x4s behind and walk,
                      carrying all our equipment with us. As
                      we climbed the last hundred metres or
                                                                   filters. Filters were also used to collect
                                                                   larger volcanic aerosols (more than one
                                                                   micrometre), which are often made up of
                                                                                                                  “   The scenery changed
                                                                                                                         from forests to
                      so, I really wasn’t sure what to expect      several over-grown phases (such as sili-
                      but, with the occasional waft of nasal-      cates, chlorides, fluorides and sulphates),        impressive lava-flows
                      burning acidic fumes, it started to hit      as well as mechanically generated dusts,
                      home that the day ahead was probably         and volcanic glasses thrown from the              carpeting the landscape
                      going to be a little different from my
                      usual days of computer-based research.
                         On the first day we had good weather
                      conditions, and sporting helmet, gas
                                                                   magma. Another instrument was used to
                                                                   collect the smaller volcanic aerosols (less
                                                                   than one micrometre).
                                                                      Once the instruments were up and
                                                                                                                   Each day on Etna was memorable in a”
                                                                                                                 very different way. The weather ranged
                      mask and sunglasses, we approached the       running we finally had time to stop and       from T-shirt weather to the sort of
                      north-east crater (one of the four main      take it all in. In addition to the main       weather that demands five layers and
                      vents on Etna) for the first time. Peering   open vents, the summit was dotted with        thick waterproofs as well as gloves.
                                                                   many fumaroles (smaller vents through         Visibility ranged from being able to see
                                                                   which gases escape) covered with vividly      across to the Aeolian Islands off the north
                                                                   coloured encrustations of yellow, orange      coast of Sicily, to not being able to see
                                                                   and white crystals.The noise at the sum-      your own feet. But all in all the experi-
                                                                   mit was similar to a kettle boiling; the      ence of Etna was unforgettable and
                                                                   whistling rush of hot gases accompanied       though there were times when it was
                                                                   the ever-present drone of our equip-          cold, windy and damp, and when every-
                                                                   ment. Lunch consisted of a well-timed         thing tasted of acid (always bound to put
                                                                   removal of the gas mask, a quick mouth-       you in a bad mood), I look back and
                                                                   ful of food, followed by a speedy replace-    think, this is a pretty cool thing to be
                                                                   ment of the mask to avoid inhaling a          doing for my PhD.
                                                                   lungful of volcanic gas.
                                                                      Mid-afternoon, the clouds set in and              Rob Martin is a PhD student in the
                       Mount Etna from a distance
                                                                   so after several hours of sampling we                     Department of Earth Sciences

        22                                                                       luesci                                                       Lent 2006
                                                                                                                                                                 I n i t i at i ve s
                             Building with Biology
                                   Cambridge students build on nature s designs
In the summer of 2005 we worked                   Our team decided to explore the feasi-                    we discovered a malE mutant that pro-
within a team of Cambridge under-              bility of controlling the movement of bac-                   duced an unstable form of MBP that dis-
graduates to produce the UK’s first            terial cells (we used Escherichia coli as our                appears within 45 minutes (a relatively
entry for the annual International             model system). We began by looking at                        short time period in terms of protein life-
Genetically Engineered Machine                 the sugar maltose, which is both an ener-                    span). Incorporating the malE mutant will
(iGEM) competition. The competition            gy source and a chemoattractant (certain                     be the next stage of the project. Our com-
involved 13 universities from around           bacterial strains are attracted to maltose,                  plete genetic circuit is shown in the box
the globe. The challenge was to engi-          and will actively move towards areas                         below (where some of the detail behind
neer living bacteria that could per-           where it is in high concentration). Thus,                    the circuit is also explained).
form a specific task.                          we hoped that by controlling the cell’s                         The ‘wet lab’ phase of the project was a
   Each team was given a ‘toolkit’ of          response to maltose, we could control the                    great experience for us all, especially the
standard, interchangeable parts called         movement of E. coli towards maltose.                         engineers who had never even used a
‘BioBricks’. Each BioBrick is a DNA               To exert a degree of control over the                     pipette before. Unfortunately the end of
sequence with a known function; the            movement of E. coli cells via a natural                      the summer came all too soon, and we
DNA may code for genes or regulatory           pathway, we needed to be able to establish                   had to travel to Cambridge, Massachusetts
components (for example gene promot-           on and off switches for chemotaxis (the                      to present our work at the Massachusetts
ers). The teams were to design a simple        directed motion of an organism toward                        Institute of Technology.All the competing
biological system using BioBrick com-          favourable environmental conditions, and                     teams congregated to present their proj-
ponents and then implement their               away from those deemed unfavourable).                        ects in front of some of the biggest names
design in the laboratory using genetic         We achieved this by adapting a ‘genetic                      in the field. It was truly amazing to see
engineering techniques.                        switch’ to control the expression of the                     what each team, mostly or solely com-
   Tried and tested BioBricks are main-        bacterial gene malE, which encodes the                       prised of undergraduates, could develop
tained in an online Registry of Standard       sequence information for Maltose                             in such a short time, with the quality of
Biological Parts (, a     Binding Protein (MBP). MBP is required                       the work often rivalling that seen in pub-
kind of virtual Lego box. To construct a       for the detection of maltose and is essen-                   lished journals. After the presentations
bacterial temperature sensor, you can          tial for directed movement towards the                       came the awards ceremony. The
simply order the appropriate compo-            sugar. To switch on MBP production we                        Cambridge team walked away with some
nents from the Registry and put them           used a genetic switch, which utilised                        of the most valued awards, including
together in a bacterial cell. Each             DNA recombination, that enabled the                          ‘Most Effective Approach’,‘Best Data and
BioBrick DNA sequence is flanked by            malE gene to be expressed in response to                     Data Visuals’ and, last but not least, the
four sites at which specific restriction       a specific chemical stimulus—isopropyl-                      ‘Best Uniform’ award!
enzymes can cut. This means that by fol-       beta-D-thiogalactopyranoside (IPTG).
lowing a series of simple laboratory pro-         Designing the ‘off ’ switch for chemo-          
tocols, BioBricks can be assembled             taxis proved to be more difficult, as MBP
together on a plasmid (a circular piece of     takes a long time to degrade once it has                            James Godman is a third year Natural
DNA that can replicate independently of        been produced. This means that after                           Scientist specializing in Plant Sciences; Alice
the bacterial chromosome) and this can         removal of the chemical stimulus (IPTG),                       Young is a third year Natural Scientist spe-
then be transformed into a bacterial cell      MBP is still present and able to detect                             cializing in Zoology; James Brown is a
to test the BioBricks for functionality.       maltose. Following further investigation,                                                fourth year Engineer

  Bacterial Traffic Lights
   A ‘traffic light’ system was used to allow the bacterial response
  to maltose to be visualized.This utilised the regulated produc-
  tion of red, green and orange fluoresecent proteins to indicate
  whether or not cells were capable of carrying out chemotaxis.
     Initially, the E. coli cells constitutively expressed the gene
  mCherry which encodes a red fluorescent protein. Expression
  of mCherry is driven by a gene promoter within the Flipase
  Switch (bottom left).This promoter allows expression in one
  direction only: either mCherry or malE can be expressed at
  one time, but not both.Thus, red cells do not produce MBP
  and cannot detect maltose or move towards it: chemotaxis
  cannot occur in these cells.
                                                                       James Brown

     Following addition of the chemical stimulus IPTG (which
  was used to initiate chemotaxis), expression from the pLac
  promoter begins (top left).This leads to the production of the
  protein cI, which in turn activates production of the proteins
  c1434 and Hin. Hin acts on the Flipase Switch and stimulates                          The production of c1434, which represses Hin production,
  ‘flipping’ of the switch into the opposite orientation. This                       acts as a negative feedback loop; it prevents the production of
  results in expression of malE instead of mCherry, and also in                      too much Hin and thus prevents continuous ‘flipping’ of the
  production of Green Fluorescent Protein (GFP): the cells are                       Flipase Switch. If maltose is present, MBP binds to it, and this
  now green, and are producing MBP.Thus the cells which can                          complex is able to activate production of the orange fluores-
  produce MBP (and, therefore, detect the presence of maltose)                       cent protein mOrange, making cells that have detected malt-
  are green.                                                                         ose (and will move towards it) appear orange.                                           luesci                                                                                        23

                                                              An Original Thinker
                                                        Varsha Jagadesham explores the legacy of Frederick Hopkins
                                                        expertise to purifying the known food
                                                        groups: proteins, carbohydrates, fats and
                                                        minerals. Hopkins was thus able to con-
                                                        duct systematic feeding experiments on
                                                        mice to determine the importance of
                                                        each food group, using diets of known
                                                        composition of purified food groups.
                                                           It had already been demonstrated by
                                                        the Dutch doctor Christiaan Eijkman
                                                        that the disease beriberi was caused by a
                                                        specific deficiency in diet.The substances

                                                                                                                                                   All images courtesy of the Department of Biochemistry
          Eastbourne, 20 June 1861: Frederick           lacking were then known as accessory
          Gowland Hopkins is born. The future           food groups but are now called vitamins.
          will see him make a resounding con-           They did not belong to any of the
          tribution to science for which he will        known food groups but were believed to
          later be awarded the Nobel Prize for          be just as important for growth.
          Physiology or Medicine. It will also          However, Eijkman’s findings alone did
          watch as he establishes the                   not herald the beginning of medical
          Department of Biochemistry in                 research into dietary deficiency diseases,
          Cambridge and sets the remit of               as understanding of this new field was
          modern biochemical research, here             rudimentary and it was difficult to
          and worldwide.                                demonstrate conclusively the essential
             Hopkins showed a scientific curiosity      nature of vitamins for growth.
          from an early age. When he was a young           With his systematic feeding experi-
          boy, his mother presented him with a          ments on mice, Hopkins was able to
          microscope which he used to study the         show definitively that vitamins were          First issue of Brighter Biochemistry
          many forms of life on the Eastbourne          required for normal growth just like the
          seashore. At City of London School, he        basic food groups. Thus, Hopkins                Hopkins’s 1912 paper on the physiolog-
          excelled in several subjects but it was his   demonstrated the physiological necessity     ical necessity of vitamins was considered a
          performance in the sciences which             of vitamins, thereby closing the gap in      seminal work in nutrition and biochemi-
          brought him particular recognition: he        this body of work.                           cal research. But it set another, more sub-
          was top of his class in chemistry and by         The work of Hopkins and Eijkman           tle precedent: a move from crude
          the age of 17, he had already published a     gave rise to a new area of research, aimed   output/input studies to investigations at
          paper in The Entomologist, a journal on       at elucidating the role of vitamins in       the level of biological processes and indi-
          the science of insects.                       growth and dietary deficiency diseases.      vidual chemically defined molecules. In
                                                        This contribution to medicine and soci-      short, what we now know as modern bio-
                                                        ety was recognised in 1929, when the         chemical research. Hopkins was an early

          “       Hopkins defined
                 biochemistry as a
                                                        pair were awarded the Nobel Prize for
                                                        Physiology or Medicine for the discov-
                                                        ery of vitamins.
                                                                                                     champion of the importance of such
                                                                                                     research, and in 1913, he addressed the
                                                                                                     British Association for the Advancement
                 science combining                         This Nobel Prize winning work was         of Science with his famous lecture, The
                                                        conducted in the Physiology Laboratory,      Dynamic Side of Biochemistry.
                chemical rigour with                    Cambridge, a place where physical               In this lecture, Hopkins defined bio-
                 biological instinct                    approaches, rather than chemical, were       chemistry as a science “combining chem-

            After leaving school, Hopkins trained
          in analytical chemistry, graduating from
                                                        used to study physiological problems.
                                                        Here, Hopkins’s chemical research was
                                                        seen as an unnecessary drain of limited
                                                        resources. Pressure grew to establish a
                                                                                                     ical rigour with biological instinct”. He
                                                                                                     expounded the simplicity of the chemical
                                                                                                     events that underlie biological processes,
                                                                                                     explaining the interdependence of these
          University College London in the short-       separate biochemical chair for Hopkins. It   processes within the cell and their
          est possible time. He next embarked           took some persuasion on the part of          “underlying unity” in all organisms. He
          upon a medical degree at Guy’s Hospital,      Hopkins and his colleagues but eventual-     stressed the importance of fundamental
          London, remaining there after qualifying      ly, in 1914, the Cambridge Department        research into all living organisms, in a
          to work as a demonstrator in toxicology       of Biochemistry was established with         challenge to the contemporary view that
          and physiology. Whilst in London, he          Hopkins as its first Professor.              biochemical research was used by medi-
          began using his chemical training to
          investigate biological substances associat-
          ed with health and disease, work that
          earned him an appreciative and curious
          audience of scientists.
            In 1898, upon invitation, Hopkins
          moved to the Physiology Laboratory,
          Cambridge, to develop this chemical
          analysis of biological substances. Hopkins
          had great experience in purifying pro-
          teins, thanks to his years at University
          College London. In the Cambridge
          Physiology Laboratory, he turned this

   24                                                                luesci                                                          Lent 2006
cine for medicine. Hopkins thus defined
the boundaries of contemporary bio-
chemical research. In 1914, as the Chair
of the Department of Biochemistry, he
was able to pursue this vision.
   Research in the Department of
Biochemistry was diverse in nature.
One laboratory was investigating bio-
chemical embryology; another, the
catalysis of specific reactions by
enzymes; another, muscle biochemistry.
Hopkins encouraged a ‘free-for-all’
ethos in the Department, in which
members were free to choose their own
research topics and collaborate with
external laboratories. This vision came
to be one of the strengths of the
Department—now              internationally
recognised—and its alumni: by the time
of Hopkins’s death in 1947, some 75 of
its past members held professorial chairs
around the world.
   The atmosphere in the Department is
aptly captured in editions of Brighter
Biochemistry, the in-house journal at this
time. In the first edition, editors write of
“the wealth of imagination that constant-      research and remove the administrative       for what biochemical research could and
ly pervades our laboratory”, and the fol-      pressures from Hopkins. But these were       should include, and his belief in bio-
lowing pages reveal a trove of satire,         futile, blocked by Hopkins’s resistance      chemistry as an autonomous science, he
poems and ditties, as well as papers, such     and the strength of support from mem-        contributed to science and society once
as ‘The Direct Determination of the            bers of his Department.                      again—through his own work and that of
Mentality of the Normal Adult’. It is             Hopkins’s beliefs were propagated         the many who took his thoughts with
apparent that members of the                   through members of the Department and        them. Truly, Hopkins was “the father of
Department believed wholeheartedly in          through propaganda he published him-         British biochemistry”.
Hopkins’s vision.                              self. However, what was called the golden
   However, Hopkins’s leadership and           age of the Department came to an end          Varsha Jagadesham is a fourth year Natural
the nature of the departmental research        with Hopkins’s death in 1947, and the               Scientist specializing in Biochemistry
did not go unquestioned. There were            movement of members out of the school.
mutterings regarding the significance          It was some time after the Second World                    
and coherence of so many lines of              War when Hopkins’s vision of biochem-
research, and about the amount of time         istry began to resonate in laboratories
Hopkins was required to spend on               once again, as money started to pour into
                                                                                             Further Reading
administrative duties on account of this.      the life sciences, enabling diverse funda-    Cambridge Scientific Minds edited by Peter
There was also the persistent challenge        mental research into all organisms which      Harman and Simon Mitton
that although fundamental biochemical          continues to this day.
research was important, medical objec-            With his role in the discovery of vita-    Hopkins and Biochemistry by Harmke
tives should still exist. Murmurs of dis-      mins, Fred Hopkins contributed to both        Kamminga
content led to actions to re-orient            science and society. But with his vision
Arts & Reviews
                                   Problems in the Pipeline
                 Europe s scientists pull out all the stops as its historic organs fall silent. Mark Turner investigates
                 The churches of continental Europe har-                                                                    ern concession to parishioner comfort
                 bour some of the world’s finest and most                                                                   may be driving off acid in the new wood
                 ancient pipe-organs. These instruments,                                                                    faster than ever before.
                 originally built in the fifteenth, sixteenth                                                                  Catherine      Oertel       at    Cornell
                 and early seventeenth centuries by such                                                                    University, collaborating with GOArt,
                 renowned organ builders as Friederich                                                                      employed a range of spectroscopic tech-
                 Stellwagen and Arp Schnitger were, in                                                                      niques to probe organ pipe composition,
                 their time, some of the most sophisticat-                                                                  focussing especially on X-ray fluores-
                 ed machines ever built and stand as shin-                                                                  cence spectroscopy. Here, an electron
                 ing examples of both technological and                                                                     microprobe bombards the sample in
                 artistic achievement. Instruments such as                                                                  question with a harmless stream of elec-
                 the 1467 Stellwagen organ in the parish                                                                    trons, causing X-ray emission, with each
                 church of St Jakobi’s in Lübeck,                                                                           element in the pipe’s composition giving
                 Germany are prized for their unique                                                                        a characteristic wavelength fingerprint.
                 tone qualities: aficionados rate this organ                                                                Pipe alloy composition also seems to be
                 as one of the finest in the world for the                                                                  an important factor in determining sus-
                 performance of Renaissance and early                                                                       ceptibility to corrosion. Almost all affect-
                 baroque repertoire. The news therefore                                                                     ed instruments in continental Europe
                 that the largest pipes in this important                                                                   were built in the Northern German tra-
                 instrument were quite literally losing                                                                     dition, using lead alloys with a low tin
                 their voice, sent shockwaves through the                                                                   content of 1.5–2%. Lead is alloyed with
                 organ playing and building community.                                                                      tin, both to harden the organ pipes and to
                 Inspection of the instrument revealed                                                                      add lustre. Tin was extremely scarce and
                 the cause: small holes in the walls of the                                                                 expensive at the time, and so European
                 pipes. The organ had an acute case of                                                                      builders were directed by frugality. It is
                 lead corrosion.                                                                                            indeed the low tin content in the pipes of
                    As word of the Lübeck Stellwagen                                                                        prized historic organs that contributes to
                 organ’s symptoms spread throughout                                                                         their unique tone colour. This explana-
                 Europe, it became apparent that this was                                                                   tion is corroborated by the fact that
                 not an isolated case: similar rapid corrosion                                                              British historic organs have so far not
                 was afflicting historic organs across the                                                                  been affected by rapid pipe corrosion. At
                 continent.                                                                                                 the time, Cornwall was Europe’s major
                    The pipework of these organs is craft-                                                                  source of tin: British organ builders
                 ed from lead, which is well known to                                                                       therefore had ready access to a cheaper
                 corrode gradually under atmospheric                                                                        source of the metal, and their pipework
                 conditions. However, the corrosion pat-                                                                    often contains up to 20% in the alloy.
                                                                                                              Mark Turner

                 tern in Lübeck was entirely new, charac-                                                                      Interestingly, addition of tin to the
                 terised by the formation of a white                                                                        pipework alloy is not thought to directly
                 chalky residue in the pipe interior which                                                                  provide resistance to corrosion. Optical
                 eventually eats through the pipe entirely.      the bellows and the windchests on which                    and electron microscope analyses by
                 In 2003, research engineer Carl Johan           the pipes themselves sit. In each of the                   researchers at the University of Bologna
                 Bergsten from the Organ Art Centre at           corroding instruments, restoration work                    have shown that pipework with a low tin
                 Sweden’s       Gothenburg         University    involving replacement of oak wood had                      content tends to have higher levels of trace
                 (GOArt) assembled a team of chemists,           taken place in the recent past.                            impurities such as bismuth and antimo-
                 metallurgists, organ builders and histori-         As wood ages, the cellulose forming its                 ny—additives which can subtly alter the
                 ans, founding the Corrosion of Lead and         cell walls tends to break down releasing,                  microstructure of the alloy. It could well be
                 Lead-Tin Alloys of Organ Pipes in               amongst other chemicals, both formic                       that understanding the effect of these trace
                 Europe project, or COLLAPSE, to inves-          and acetic acid.When fresh wood is used                    impurities holds the key to unravelling the
                 tigate. Chemical analysis of corroded and       to line wind chests and bellows, this                      mystery of organ corrosion.
                 uncorroded pipework samples quickly             organic acid is released directly into the                    Meanwhile, can anything be done to
                 began to yield clues suggesting that, of all    organ’s wind supply, from where it is car-                 safeguard these instruments? Catherine
                 things, well-meaning restoration may lie        ried into the pipes. Archaeologists and                    Oertel favours either the development
                 at the heart of the problem.                    conservationists have long known the                       of a coating to be applied to wood com-
                    The corroded lead contained higher           effect of oak on lead artefacts, and will                  ponents inside the organ, preventing the
                 than normal levels of organic acids—            always avoid storing such items in oak                     escape of organic acids, or the use of
                 known to cause the rapid oxidation of           drawers or cabinets—but the organ                          passive filtration systems to remove them
                 lead to lead hydroxycarbonate and lead          building community has been slow to                        from the wind supply. Bergsten at
                 hydroxyacetate, responsible for the             make this link.                                            GOArt hopes to produce a protective
                 observed white residue. Further investi-           In the five hundred year lifetime of a                  coating for the pipes to protect from
                 gation and air sampling indicated the           historic organ such as that in Lübeck,                     corrosion. For now, however, the
                 presence of acetic acid in the airflows of      the interior wood of the organ will have                   pipework remains irreplaceable; and as
                 the stricken instruments.                       been changed several times. So the ques-                   more and more organs gradually lose
                    Why had this rapid corrosion suddenly        tion rises once again, why is this corro-                  their voice, organ enthusiasts can only
                 appeared in instruments, some of which          sion only now apparent? Svensson’s                         hope that progress is swift.
                 had otherwise survived for five hundred         work suggests that church central heat-
                 years? A possible source of acetic acid in      ing may be to blame: a recent addition                             Mark Turner is a PhD student in the
                 pipe-organs is the oak wood used to line        to many European churches, this mod-                                         Department of Chemistry

      26                                                                      luesci                                                                      Lent 2006
Dr Hypothesis

                                            Dr Hypothesis
                                        Please email your queries to for your chance to win a £10 book voucher

                Dear Dr Hypothesis,                                and colourless, so this should not cause
                I exist mainly on a diet of toast, but, as         you any undue embarrassment. Spraying                Dr Hypothesis asked:
                my room is rather squalid and crowd-               deodorant simply under your arms
                ed, I often lose bits of toast down the            should be enough to create a fragrant and            “When I hold a copy of BlueSci up to a mirror
                side of the bed or beneath a book.                 favourable impression on your interview-             the writing appears back-to-front. Given that
                Long contemplation of old toast has                ers. Good luck!                                      the mirror doesn’t seem to have a preferred
                made me wonder: why is toast crisp                                                                      direction, why doesn’t the writing also appear
                and crunchy when it comes out of the                upside down?”
                toaster, but soggy shortly afterwards?
                                           Squalid Sarah                                                                One of our readers answered: The key to
                                                                                                                        this question is to appreciate that the mirror
                DR HYPOTHESIS SAYS:                                                                                     does not actually laterally invert anything.
                This is a tough question as I am not aware                                                              Rather, it produces, at each point in the mir-
                of any scientific studies describing the                                                                ror, an image of whatever is directly in front
                properties of toast! However, I believe                                                                 of this point. In order to hold a copy of
                that the cause of this phenomenon is the                                                                BlueSci up to a mirror it is necessary to
                moisture present within the bread.When                                                                  rotate the magazine by 180¡ about a verti-
                you toast the bread it will heat up, turn-                                                              cal axis. It is this rotation that performs the
                ing this water into steam.The toast cools                                                               lateral inversion.To see how this is the case,
                once it comes out of the toaster, condens-                                                              imagine repeating the experiment with a
                ing the water back into liquid form and                                                                 copy of the magazine printed on a clear
                making your previously firm toast appear                                                                plastic sheet. Upon holding up the sheet in
                damp.This explains the benefit of a toast                                                               front of the mirror, with the text facing you,
                rack: by holding the toast vertically, the                                                              the text in the mirror is also the correct way
                rack promotes the loss of steam—there is                                                                round. Then, rotate the sheet to face the
                then less water to condense and so your                                                                 mirr o r n ow both the text on the sheet
                toast will remain firmer. Maybe a rack                                                                  itself, and the image of the text in the mir-
                would be a good investment for you,                                                                     ror, appear laterally inverted.
                                                                                                                                A Weighty Decision
                Dear Dr Hypothesis,
                                                 _20Rack           I had just finished tucking into a                   Dr Hypothesis research assistant Tom Pugh
                                                                   greasy meal of fish and chips when I                 challenges you to try your hand at this
                                                                   noticed that I could practically see my              mathematical mystery:
                Dear Dr Hypothesis,                                copy of BlueSci through the once
                I am a biology student graduating in               opaque paper where the oil had
                                                                                                                        You find yourself in a room with 20 bags of
                the summer. I am worried about sweat               soaked through it. Why does this hap-
                                                                                                                        gold coins.You can take one bag away with
                patches when going for job interviews              pen and why does it not work with
                                                                                                                        you. However, 19 of the bags contain gold-
                in the next couple of months. As I’m               things other than paper?
                                                                                                                        plated coins, each of which weighs one
                sure you’re aware, we are all sweating                                     Greasy Garrett
                all the time over nearly our entire                                                                     ounce. Only one bag contains solid gold
                bodies, but we only put anti-perspirant            DR HYPOTHESIS SAYS:                                  coins, each weighing two ounces. A weighing
                under our arms. To prevent myself                  The fibres in a piece of paper, such as a            scale is provided, but you are only allowed a
                feeling uncomfortable, surely I should             page of BlueSci, form a lattice, that is not         single weighing to identify the bag containing
                apply deodorant to my entire body? Is              quite perfectly arranged at the molecular            the solid gold coins. How can you be sure to
                it worth my time doing this, or are                level.This means that the light which hits           come away with the money?
                there any shortcuts I can take?                    the page is scattered and the unabsorbed
                                       Nervous Nancy               rays are reflected, but at a wide range of           Visit for the answer.
                                                                   angles relative to the angle at which they
                DR HYPOTHESIS SAYS:                                hit the page. Therefore, the light and the
                There’s no need to worry about this,               page will appear white. If grease gets into
                Nancy, as there is sound scientific reason-        the fibres, it produces a more uniform lat-
                ing behind what I’m about to explain.              tice, so that the scattering of the light
                You’re correct in saying that our bodies           becomes more even.This actually recon-
                                                                                                                                                                          Illustrations by Lizzie Phillips

                perspire over most of the surface, but the         structs the light wave on the other side of
                composition of sweat can vary. Only                the page, so it is now transparent! This
                underarm sweat contains proteins and               phenomenon is only possible with paper,
                fatty acids (which leads to the stains             as opposed to materials like metal,
                you’re afraid of) and only this type of            because only paper is made up of fibres
                sweat is capable of supporting bacteria            that can interact with grease in this way.
                that produce the bad smell. Fortunately
                most other types of sweat are odourless              

                Think you know better than Dr Hypothesis?
                He challenges you with this puzzle: Why do the geographic and magnetic north poles not strictly coincide?
                Please email him with your answers, the best of which will be printed in the next issue of BlueSci.

     28                                                                            luesci                                                               Lent 2006
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