BlueSci Issue 05 - Lent 2006 by BlueSci

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Issue 5

Lent 2006

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Astrobiology The search for alien life

AIDS: 25 Years On Past, present and future

Chocolate Why do we love it?

• Grapefruit • Dr Hypothesis • • Probiotics • Quantum Computers •

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Lent 2006

Issue 5

contents

Feature s Quantum Calculations

Tristan Farrow introduces the computers of the future.................................................................

DNA Damage and Repair

Zoe Smeaton highlights a Cambridge scientist s efforts to revolutionize cancer treatment..

Chocolate s Chemical Charm

Dhara Thakerar explains the science of chocolate...........................................................................

Are We Really Alone?

Gemma Simpson explores the universe for possible signs of life.................................................

Probiotics: More Pros than Cons?

Louise Woodley on the benefits of ingesting live bio-cultures.......................................................

The Sixth Sense

Juliette McGregor uncovers the artwork we never knew we could see, Haidinger s Brush..

Citrus Paradisi

Chi Ngai Chan examines the link between grapefruit juice and Viagra.......................................

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

From The Editor Welcome to the fifth edition of BlueSci. Did you over-indulge in festive chocolates this holiday season? If so, you can ease those feelings of guilt by reading about the science behind the reported health benefits of chocolate in CHOCOLATE’S CHEMICAL CHARM. If this whets your appetite for more food-related science, on page 19, Chi Ngai Chan highlights the startling effects of grapefruit juice on drug metabolism, and in PROBIOTICS: MORE PROS THAN CONS? we question just how beneficial those ‘friendly bacteria’ really are. To coincide with the 25th anniversary of the first recorded case of AIDS, our regular FOCUS section examines the current status of HIV and AIDS research, and looks ahead at what the next 25 years may yield. In ARE WE REALLY ALONE?, Gemma Simpson turns to the field of astrobiology to look for evidence of alien life-forms, while in PROBLEMS IN THE PIPELINE, Mark Turner explains why organ enthusiasts

have turned to scientists in their attempts to save historic pipe-organs across Europe. Of course, the much-loved DR HYPOTHESIS is back on page 28 to answer your science-related questions. In addition, new for issue 5, the good doctor has a logic puzzle for you—to get those grey cells working! The solution is available on our website, www.bluesci.org, where you can also find extra articles. Once again, we were impressed by the quality of submissions we received for issue 5, from students and post-docs across the University. If you feel you have what it takes to write for BlueSci, or you wish to get involved in editing or producing the magazine, we would love to hear from you: either email enquiries@bluesci.org or visit BlueSci Online for more details. I hope you enjoy reading issue 5. Tamzin Gristwood issue-editor@bluesci.org

From The Managing Editor Happy New Year! Things have been very busy for BlueSci over the past few months. Our first birthday party was a big success—many thanks to all who came. Partly as a result of this, Nicola Buckley, one of the Cambridge Science Festival coordinators, has set up an informal science outreach group which has since met to discuss how we can unify our efforts to reach out to local schools. If you would like to join us, please contact Nicola at njb1010@admin.cam.ac.uk. BlueSci was also represented as part of our parent society CUSP at the Communicating European Research conference (CER2005) in Brussels in November. We received some extremely

positive feedback, as well as learning about other science communication projects across Europe. See www.cusp.org.uk for some photos and videos of our stand! Finally, this issue sees the addition to BlueSci Online of our news and events service, which will be updated fortnightly with Cambridge science stories, as well as having a comprehensive listing of sciencerelated events. Please bookmark our website www.bluesci.org and remember to check regularly for what’s going on. Have a scientifically enlightening 2006! Louise Woodley managing-editor@bluesci.org

Editor: Tamzin Gristwood Managing Editor: Louise Woodley Submissions Editor: Ewan Smith Business Manager: Chris Adams Design and Production Production Manager: Jonathan Zwart Pictures Editor: Sasha Krol Production Team: Sheena Gordon, Jon Heras, Ryan Roark, Helen Stimpson,Tom Walters

Section Editors News Editor: Fiona McCahey News and Events Team: Laura Blackburn, William Davies, Michael Marshall, Richard van Noorden, Emily Tweed Focus: Tamzin Gristwood, Jonathan Zwart Features: 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 History: Varsha Jagadesham Arts and Reviews: Owain Vaughan Dr Hypothesis: Rob Young Publicity: Lizzie Fellowes-Freeman CUSP Chairman: Bj rn Ha§ler ISSN 1748-6920 enquiries@bluesci.org

Varsity Publications Ltd 11/12 Trumpington Street Cambridge, CB2 1QA Tel: 01223 353422 Fax: 01223 352913 www.varsity.co.uk business@varsity.co.uk BlueSci is published by Varsity Publications Ltd and printed by Cambridge Printing Park. All copyright is the exclusive property of Varsity Publications Ltd. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without the prior permission of the publisher.

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Cambridge News

Cambridge News Cambridge’s Computers and CERN

WHOLEheart

Since 2001, the University of Cambridge has been one of 19 UK universities collaborating with the European Organization for Nuclear Research (CERN) to construct the GridPP—a vast computing grid built to handle the extensive amount of data that will be produced by CERN’s new particle accelerator, the Large Hadron Collider (LHC). The LHC is expected to be ready in 2007. It is being built in a circular underground tunnel, 27 kilometres in circumference, straddling the Swiss and French borders. When completed, it will be the largest particle accelerator in the world and will be used to replicate conditions similar to those present shortly after the Big Bang. It is hoped that it will resolve many outstanding questions in particle physics, such as whether the hypothetical Higgs boson actually exists. If it does, it would aid the understanding of why fundamental particles—such as quarks and neutrinos—have the masses they do. The University of Cambridge has been a key collaborator in the construction of the GridPP. Rather than build a dedicated supercomputer to deal with the 10 million gigabytes of data that 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 the UK. The Cambridge effort is being headed by Professor Janet Carter of the Cavendish’s High Energy Physics group. MM www.gridpp.ac.uk http://public.web.cern.ch

How does the food you eat affect your health? If you would like to find out, researchers at the MRC Dunn Human Nutrition Unit in Cambridge are currently recruiting for WHOLEheart, a study into the effect of carbohydrates on the body, including blood cholesterol levels and heart health. Scientists at the Unit work on all aspects of human nutrition, from the health of our bones to nutritional epidemiology.With around 200 studies on the go at any one time, the Unit relies on an army of volunteers to help determine if we really are what we eat. In collaboration with other organisations such as the Food Standards Agency and the EU the Unit also works to reduce public confusion by providing sound nutritional advice to the media, food industry, government, and health professionals. In collaboration with the University of Newcastle, the WHOLEheart study will run through to February 2007. “We hope that we will be able to develop a positive public health message to inform people what they should be eating” says Katherine Chan, who is recruiting for the project. If you are interested, contact katherine.chan@mrchnr.cam.ac.uk or 01223 437660 for more information. LB Do you want to meet a qualified nutritionist? As part of Cambridge Science Week, you will have the chance to meet a panel of qualified nutritionists for no nonsense, simple advice on what to eat. 5 pm, Saturday 18 March 2006, Michaelhouse Café.

Cambridge University Scientific Society – Michaelmas 2005 Talks

Cong Cong Bo

Professor Sandra Chapman: Art Meets Science in Antarctica An astrophysicist by training, Professor Sandra Chapman demonstrated her fine hand for art and keen eye for photography in a talk with a difference. Last year, she realised her dreams of travelling to Antarctica by circling the continent aboard a research ship. During her expedition, she masterfully captured the brilliant blue of ice caves, the pale pink of distant mountains, and the connection

between the hostile climate and beautifully unspoilt landscape. We were treated to the most charming of travelogues from a truly unique personality, whose insight into the interplay of science and art was delightfully refreshing. Professor Tom Mullin: Patterns in the Sand (pictured) Introduced as the world record holder for stacking the greatest number of upsidedown pendulums, Professor Tom Mullin attracted a huge crowd.The segregation of granular mixtures is relevant not only to physicists, geologists and engineers, but also lovers of muesli: the Walnut Effect explains why shaking your cereal box vertically will make the fruit rise, while shaking the box horizontally will make it sink. Professor Mullin is internationally acclaimed for his work on the application of modern mathematical ideas to chaos and complicated flows. He has most recently investigated the flow of granular materials such as sugar and poppy seeds, revealing a rich variety of novel and intriguing phenomena. Professor Michael Green FRS: String theory: Unifying Particles, Forces and Space-time Quantum physics. String theory.That ohso-elusive grand unified theory. All topics

that have captured many an imagination, yet which under the surface, are often opaque. Professor Michael Green, widely known for sparking the First Superstring Revolution in 1984, presented the Society with a wonderfully clear introduction to string theory, from its beginnings as a mathematical convenience to the cuttingedge of today and its far-reaching implications. Let us all be grateful that of the 26 dimensions he described, it seems we need only negotiate four. Cong Cong Bo All talks are held in the Pharmacology Lecture Theatre, Tennis Court Road. More details are available on our web site www.scisoc.com.We have a great lineup of speakers for next term, including: Pioneering embryologist Dame Anne McLaren of the Wellcome Trust and Cancer Research UK Gurdon Institute, speaking on human cloning; Cosmologist Dr Martin Bucher of Université Paris-Sud, discussing dark energy; Psychologist Dr Peter Thompson, Director of the Visual Perception Library and originator of the Thatcher Illusion; Accomplished botanist Professor Peter Crane, Director of Kew Gardens.

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 www.youramazingbrain.org.

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Lent 2006

C a m b r i d g e N ew s

Around 200 million people worldwide suffer from schistosomiasis, a debilitating and sometimes fatal disease caused by parasitic 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 something 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 African photos taken by Dr Booth.The first community project 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 community in Uganda” he says.The group has studied some of these communities for over 30 years and often treats children of the people who were involved in the study when it first began. Using a multidisciplinary approach, the group is researching many aspects of schistosomiasis, including trying to find out why some people are more seriously affected than others by the disease. LB

Mark Booth

To support the Matangini project, visit www.matangini.org.uk and www.photoboxgallery.com/matangini

John Hillier

Matangini Project

Piggyback Volcanoes Young volcanoes in French Polynesia, in the south-central Pacific Ocean, could form by ‘piggybacking’ on older, otherwise unrelated volcanoes, according to new research by Dr John Hillier in the Department of Earth Sciences. He has created four new maps of the Pacific Ocean that illustrate where volcanoes have erupted in the last 160 million years. To do this, he dated 2700 of the approximately 50,000 large volcanoes in the Pacific using a map of gravity variations, which was derived by measuring 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 gravitational pull of the volcanic mass, relates to the age of the volcano. 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 expected 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 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 Charles Darwin’s theory of evolution were sown during his famous trip on HMS Beagle. However, new research by Professor John Parker, Director of the Botanic Garden at the University of Cambridge, and colleagues suggests that Darwin’s evolutionary thinking may have had its foundations in the teaching he received during his undergraduate years (1829–1831). In their article in Nature, the researchers explain that one of Darwin’s lecturers during that time was the botanist John Henslow, who is famous for his rigorous and extensive research into the nature of plant species. He assembled a herbarium of over 10,000 plants and organised them uniquely in order to emphasize variation within species—though believing, as everyone else did, that species were created and stable. Henslow enlisted Darwin as one

news@bluesci.org

of his collaborators on the herbarium and also arranged his place on HMS Beagle. Professor Parker and colleagues have found evidence to suggest that on HMS Beagle Darwin began looking at plants and animals using the conceptual framework he had absorbed from Henslow. Though Darwin’s assumptions were later to change, Henslow’s instruction was a vital influence in his noting of species variety. It formed the basis for his eventual understanding that varieties are in fact ‘new-forming’ (i.e. evolving) species. “It’s a great example of how influential teaching can be in forming the mind of the undergraduate. This undergraduate teaching certainly launched Darwin with the ability to think for himself about the nature of species” said Parker. RN Nature, 436: 643–645 (2005) www.nature.com

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Focus

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 for Disease Control and Prevention (CDC) publish an article by doctors in New York and Los Angeles reporting a cluster of unusual diseases among young gay men. The men have unexplained defects in their immune system making them susceptible to rare forms of pneumonia, cancer and fungal infection. Clinicians and scientists alike are baffled, and theories abound as to the origin of what seems to be an entirely new disease. Twenty-five years on, and this disease is estimated to have killed more than 25 million people. Acquired Immune Deficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), is one of the greatest threats to global public health of our time. The United Nations estimate that 40.3 million people worldwide are currently living 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 the fight against HIV. The disease was initially known as GRID (Gay-Related Immune Disorder). Some epidemiologists speculated that it was caused by use of the drug amyl nitrate, common in the gay clubbing scene.The first significant clue to the true nature of the illness was the discovery of similar symptoms in a group of injecting ¥ In 2005, there were an estimated 40.3 million people living with HIV worldwide ¥There were an estimated 4.9 million new HIV infections in 2005 ¥15—24 year olds now account for half of all new HIV infections more than 6000 become infected every day ¥ By December 2005, women accounted for 46% of HIV infected adults worldwide, and 57% of the total in sub-Saharan Africa ¥ Of the total number of HIV infected people worldwide, 95% live in the developing world ¥ By December 2004, an estimated 58,300 UK adults were living with HIV, of which 19,700 (34%) were unaware of their infection ¥ In the UK, the lifetime treatment cost of caring for someone who is HIV positive is estimated to be between £135,000 and £181,000

drug users, and later in haemophiliacs— people with a disorder in blood clotting who require regular blood transfusions. Scientists at the US National Institutes of Health (NIH) began to suspect that an infectious agent, transmitted by blood or sexual contact, was to blame. The spread of the disease to groups beyond the gay population marked a turning point in terms of its public perception.As Harold Jaffe of the CDC later remarked,“Up until then it was entirely a gay epidemic, and it was easy for the average person to say ‘So what?’ Now every-

“

remembers,“There was a lot of sentiment in the early eighties that pandemics were not possible in this day and age.” Reports began to filter in of similar cases across the world, first in Europe and then in Africa, where the disease was known as ‘slim’ due to the extreme weight loss that occurs in its later stages. This was a time of great public fear. So little was known about HIV that confusion was widespread. In the US, a young haemophiliac who contracted HIV through a blood transfusion was banned from school, whilst in the UK firemen

A young haemophiliac who contracted HIV through a blood transfusion was banned from school

one could relate.” The disease revealed previously hidden prejudices within society and formed a key rallying point for the emerging gay rights movement. By the mid-1980s, the HIV virus had been independently isolated by Luc Montagnier at the Institut Pasteur in France and Robert Gallo at the National Cancer Institute in the US. Two forms were later characterized: HIV–1, accounting for the majority of infections worldwide, and HIV–2, largely confined to West Africa. HIV is now believed to be derived from a similar virus in primates— Simian Immunodeficiency Virus (SIV)— which is thought to have ‘jumped’ into humans early in the twentieth century via the bushmeat trade in West Africa. This type of cross-species transfer is responsible for some of the most serious new infectious diseases of recent times, including hantavirus, Lassa fever and variant CJD. The possibility of a similar transfer from animals to humans is the cause of the current concern surrounding avian influenza. At that time, emerging infections were not perceived as a threat to public health. The success of antibiotics and vaccines over the past decades had created an atmosphere of complacency in which the era of infectious disease—in the developed world, at least—was believed to be over. In 1969, the US Surgeon General had told the nation that it was time to “close the book on infectious diseases”, and as William Blattner, a researcher at NIH,

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were prohibited from giving the kiss of life for fear of contagion.As The New York Times reported, “In many parts of the world there is anxiety, bafflement, a sense that something has to be done—although no one knows what.” Since those early years, the world has seen the pandemic spiral out of control. One of the reasons why the disease has spread so effectively is that there is a long delay between infection with HIV and the appearance of symptoms. The slow onset of full-blown AIDS means that people may be HIV-positive yet feel healthy and hence unwittingly spread the virus to others. From its origins in Africa and initial identification in the US, HIV has spread throughout the globe, with major new epidemics occurring in Eastern Europe and South-East Asia. There is currently no vaccine for HIV, though several candidates are undergoing trials, and no cure. The past 25 years have seen a huge increase in our understanding of HIV and AIDS, with thousands of papers published on the subject each year. However, much remains unknown, and the real challenge lies in converting the fruits of this research into practical measures for prevention and treatment for the millions living with this disease around the world. Emily Tweed is a third year Natural Scientist specializing in Pathology

Lent 2006

RNA genome

Capsid

Viruses cannot reproduce without a host cell.Although HIV can infect a variety 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.

Viral membrane

Equinox Graphics

Enzymes: reverse transcriptase, integrase, protease Surface proteins: gp120, gp41

2. Viral Penetration After binding to CD4, gp120 undergoes a conformational change. This exposes gp41, as well as a previously inaccessible looped region of gp120 that can bind to the chemokine receptor.The exposed gp41 directs the fusion of the viral membrane with the host, allowing the HIV capsid to be injected into the cell.

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

4. Reverse Transcription HIV s single-stranded RNA is converted to double-stranded DNA (around 9000 base pairs long) by reverse transcriptase, an enzyme common to all retroviruses. Reverse transcription is highly error prone making mutations, such as those leading to drug resistance, likely during this step.

5. Integration The newly synthesized HIV DNA is transported across the nuclear membrane into the nucleus, which stores the host genomic DNA. Inside the nucleus, HIV integrase directs cleavage at both ends of the HIV DNA and insertion into the host DNA.The integrated viral DNA (the provirus) now awaits activation.

1.Viral Attachment Occurs via binding of specific proteins (gp120 and gp41) on the viral surface to receptors on the cell surface. The cell surface receptors CD4 and a chemokine receptor (CXCR4) allow HIV to attach to CD4+ T-cells.

5 7 6 8

6. Protein Synthesis When the infected cell is activated to fight infection, the provirus instructs the host cell to synthesize the encoded HIV products. These include RNA, which will become the genetic material for new viruses, reverse transcriptase, integrase and protease, and HIV s structural components.

8. Budding Specific HIV proteins interact with the host cell membrane. The newly assembled capsid merges with the host membrane to form a new viral membrane. The HIV are particles released into circulation where they can infect new hosts. This cycle results in the death of the CD4+ T-cell host by an unknown mechanism.

7. Viral Assembly The new viral subunits are transported to the host cell membrane for assembly into viruses.

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).

Focus

In Africa...

ub-Saharan Africa accounts for 25.8 million (64%) of HIV infections worldwide, despite housing only 10% of the world s population. The impact of the epidemic in Africa is far different from that found in many developed countries. With infection rates in several countries exceeding 20%, HIV/AIDS poses a serious threat to the future security and stability of Africa. By crowding out other conditions, doubling bed occupancy rates and significantly increasing demand for public health care services, the AIDS epidemic has increased the burden of disease on the healthcare services by up to sevenfold. Already under-resourced systems, such as health, education and commerce, are further troubled by worker illness and death rates among trained personnel. High levels of stigma impede prevention efforts and lifesaving antiretroviral drugs (ARVs) are cost prohibitive for all but a few. As the majority of those who are infected are in their most productive years when they fall sick (aged 20—40), their family is often left without any income. In two-thirds of Zambian families in which the father died, monthly disposable income fell by over 80%. Infected individuals often return home to die, forcing family members to give up work in order to provide care. Afterwards, they must care for the children left behind. By 2010, estimates suggest the number of orphans in sub-Saharan Africa will exceed 18 million. There are signs of hope, however. In Uganda, Zimbabwe, and Kenya, infection rates appear to be declining. In other countries there are some signs that prevention and political leadership are starting to break down the stigma that surrounds the disease. Over the past few years, negotiations with pharmaceutical companies have resulted in lower costs for African countries. This provides perhaps the most hope, as it has enabled some countries to start rolling out ARVs to those most in need. However, already high infection rates, poverty, weak infrastructure, and impoverished governments mean that there is still a lot of work to be done. It also means that for the foreseeable future, HIV infection is still a death sentence for most Africans. Jennifer Gibson Centre of International Studies

HIV Transmission Routes Sexual ¥ The majority of HIV infections occur through unprotected sexual acts. ¥ The probability of transmission varies depending on the sexual act involved: 1/1000—1/10,000 for receptive vaginal sex, 1/8000 for insertive vaginal sex, 1/1000 in the case of insertive anal sex, and 1/100—1/30 for receptive anal sex. ¥ Oral sex is not without risk; numerous studies have demonstrated that oral sex can result in transmission of HIV. However, the risk of transmission is much lower than that from anal or vaginal sex. ¥ Sexually transmitted infections (STIs) increase the risk of HIV infection as they cause disruption of the normal epithelial barriers. STIs also increase risk as they result in an accumulation of HIV-infected or HIV-susceptible cells (lymphocytes and macrophages) in semen and vaginal secretions. ¥ During sexual acts, only condoms (both male and female) can reduce the chances of infection with HIV. ¥ Recent reports suggest that male circumcision can reduce HIV transmission. However, UNAIDS believes it is premature to recommend this as a preventative measure.

Blood or Blood Product ¥This mode of transmission is particularly important for intravenous drug users, haemophiliacs and recipients of blood transfusions and other blood products. ¥ Since October 1985, all blood donations in the UK have been screened for HIV antibodies. However, this is not the case in many countries; the World Health Organisation (WHO) estimates that 5—10% of HIV infections worldwide result from transfusion of unsafe blood or blood products.

Mother-to-child ¥ In the absence of treatment, there is a 15—30% risk of transmission from mother to child during pregnancy, labour and delivery. ¥ Where antiretroviral drugs are available, combined with a Caesarean section, the chance of transmission is reduced to 1%. ¥ Breastfeeding increases the risk of HIV transmission by 10—15%.

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...and in the UK

n November 2005, the Sunday papers reported the story of a man miraculously cured of HIV. Andrew Stimpson had apparently tested HIV positive in 2002, but a year later his test results were negative. If his story is true, it will be a first. But hardly any precise information about his case has been made public and most experts are treating the case with scepticism. The media tends to concentrate on such extreme cases, but the reality of life with HIV is different. Around two-thirds of people diagnosed with HIV in the UK are taking anti-HIV medication. While more and more people are able to take just two or three pills a day, some have to swallow as many as 30. The dull routine of doing this at precise times, day in, day out, is often accompanied by unpleasant side-effects like diarrhoea, nausea and depression. Little wonder that many people are not always able to adhere to their drug-regime. As a result, the treatment is less effective and drug resistant HIV develops. When this happens, treatment needs to be switched to other drugs, to which the virus is not resistant. At present there are 19 licensed drugs in five different classes, with each class attacking HIV in a different way. People with HIV who have already been through several different combinations urgently need the development of new drugs. There are now 58,000 people living with HIV in the UK this is more than ever before. A positive but partial explanation of this unhappy reality is that, despite the disadvantages of combination therapy, it is extremely effective. Indeed, since its introduction in 1996, the number of deaths caused by AIDS has dropped by over 80%. Many people who began combination therapy in 1996 are still thriving today. Nonetheless, a recent Dutch study found that men with HIV aged 25 are five times more likely to die in any given year than HIV negative men of the same age. In the absence of a miracle cure, an effective response to HIV will involve ongoing scientific and behavioural research, political action, increased resources and changes in attitudes. Roger Pebody Terrence Higgins Trust

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Scanning electron micrographs of HIV in cultured lymphocytes by C. Goldsmith

As a result of extensive research into HIV and AIDS over the past 25 years, drugs have been developed that—at least in wealthy countries—enable people to survive for many years with few, if any, symptoms. This is a far cry from the early days of the AIDS pandemic when it was only possible to treat the side-effects of the disease. Currently, anti-retroviral drugs fall into three main classes: (i) Nucleoside reverse transcriptase inhibitors. These are nonfunctional ‘building blocks’ that are inserted into the newly synthesized viral DNA and terminate its synthesis; (ii) Nonnucleoside reverse transcriptase inhibitors. Drugs which block HIV replication by targeting the viral reverse transcriptase enzyme, necessary for the synthesis of DNA from RNA; (iii) Protease inhibitors. 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. 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 mutations each time the virus replicates). This leads to fast acquisition of drug resistance and the development of a huge number of different strains of the virus. Therefore, anti-retroviral drugs must be used within strict treatment regimes, known as Highly Active Anti-Retroviral Therapy (HAART), normally involving simultaneous treatment with three or four drugs of different classes, changing to new drugs as resistance appears.Thus there is a continual pressure for new anti-retroviral drugs, especially those targeting additional stages of the viral life-cycle. In 2003, the first anti-retroviral drug to fall outside of the three existing classes became available. The drug Fuzeon inhibits fusion of the virus with the host cell membrane. Structural changes on the surface of the virus following binding to the host cell enable the glycoprotein gp41 to insert into the host membrane, causing fusion (see page 7 for a more detailed description). Fuzeon interacts with gp41 to block the fusion process. Additional fusion inhibitors are undergoing clinical trials. For example, a drug produced by

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Pfizer that binds to the host cell chemokine receptor is in phase II trials. Our increasing understanding of the HIV life-cycle continues to reveal novel targets for the development of new classes of drugs. For example, Merck Pharmaceuticals has started human studies with L-870,810, a new agent that inhibits the enzyme integrase that is essential for the integration of HIV DNA into the host genome.Also under investigation, the integrase inhibitor V-165, a pyranodipyrimidine, has shown the highest anti-viral activity in test-tube studies to date. The capsid protein HIV-1, critical for maturation of newly synthesized viral particles, is another target for drugs. Panacos Pharmaceuticals is working on the matu-

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An HIV vaccine is the Holy Grail of AIDS research

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ration inhibitor PA-457, a derivative of betulinic acid, a cheap by-product of the paper industry. However, prevention is better than cure, and a vaccine against HIV remains the ‘Holy Grail’ of AIDS research. More than 100 different HIV vaccines have been tried in animals and humans but scientists have yet to produce an effective vaccine against HIV. The rapid mutation rate of HIV makes it a formidable enemy. Another difficulty for vaccine development is that HIV particles effectively mask their outside coat proteins so that infection does not stimulate a strong antibody response. Scientists have, however, had more success in the development of vaccines that stimulate a T-cell response: the immune system attacks cells infected with HIV rather than the virus particle itself. The leading vaccine candidate is manufactured by Merck. It uses a disabled version of a common cold virus, adenovirus, to carry three synthetically produced HIV genes into the body (gag, pol and env). The immune system is tricked into thinking that the whole virus has entered the body and initiates an immune response. Early phase II trials have given very positive data: over 75% of participants developed a T-cell response to HIV and the level of response was similar to that seen 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 vaccine becomes available. Along with a concerted 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

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The Future’s Bright individual. Abstaining from ‘risky’ behaviour, or the use of condoms, are the only ways to prevent sexual transmission.There are, however, a number of cultural and social constraints on these approaches.This is a particular problem in developing countries, where women—who account for 57% of adult HIV/AIDS cases in subSaharan Africa—are often not in a position to insist on ‘safe-sex’ practices (i.e. monogamy and the use of condoms). To tackle this issue, there is a large international effort to develop microbicides, products that, in a gel, cream, film or suppository form, could be applied topically to prevent HIV transmission. On 1 December 2005, World AIDS Day, the international commitment to the development of microbicides was demonstrated by announcements from four European governments 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 microbicides in large-scale efficacy trials, and many more at various stages of testing.

It is hoped that microbicides will be available in five to seven years. The past 25 years have seen huge changes in the prevention and treatment of AIDS, particularly in the developed world. Halting the pandemic, however, will involve continued development of new and affordable treatments, alongside increased prevention of infection. The development of a vaccine, still some years in the future, is likely to be essential if HIV and AIDS are to be eradicated completely. Collette Altaparmakova is a PhD student in the Department of Pathology

http://thebody.com www.avert.org www.aids.org www.tht.org.uk www.dhiverse.org.uk www.ipm-microbicides.org www.hvtn.org www.who.int 09

Quantum Calculations

Tristan Farrow introduces the computers of the future

Energy is the source of life and all the information contained in the universe. This is because, like mass, information is not an abstract concept but a tangible quantity. Einstein showed in his famous equation, E=mc2, that mass and energy are interchangeable entities; the same can be said for energy and information. Energy and information are inextricably linked—an idea first recognised in the mid-1980s by Rolf Landauer, a researcher at IBM. It costs energy to produce information, and energy is released when information is destroyed. In the same way that mass can be measured, information can also be measured and manipulated. Pocket calculators, abacus machines and human brains do this all the time! Information cannot live disembodied and so has to be encoded in a host, physical medium; meaning that information is subject to the physical laws governing the host object.

mined by two things: the value of the input bit(s) and the type of operation performed. Computers are remarkably simple—there are only four basic logical operations, known as AND, NOT, OR and XOR, that they perform to manipulate bits rapidly. The increase in speed and memory of computers over the last few decades has been relentless as engineers have been able to pack more and more transistors onto a single microchip. However, a limit on this expansion is looming, possibly 20 years from now. As the scale of circuits becomes ever smaller, the building blocks no longer obey the classical macroscopic rules of physics, but start to obey a completely different set of rules—those of quantum mechanics—which govern the microscopic world of atoms and subatomic particles. Imagine designing the smallest computer imaginable. Instead of transistors, we could use single atoms with two dis-

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A quantum computer can perform a calculation in a single step where a classical computer needs many more

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tinct energy levels to represent our binary state, a.k.a. zero or one. As in the case of the transistor, zero could represent the atom in its non-excited or ground state, while one could represent the atom in its excited state. We could encode the atom with a zero or a one by using a well aimed laser pulse to switch the atom between its ground and excited state. We could use this as the basic building block for the ultimately miniaturised computer in the same way that transistors are used in microchips. There is a twist, however. Because atoms and other small building blocks in nature obey the laws of quantum mechanics, quantum objects, such as our atom, can happily exist in the ground and excited states at the same time. Where

Jonathan Zwart

The building unit of information in ubiquitous digital or binary computers is the ‘bit’.This can have two arbitrary values, zero or one, which can represent any given physical system with two distinct states, for example, an electric circuit switch.We can assign ‘zero’ when the circuit switch is open and ‘one’ when it is closed.The binary computer is essentially a very large network of such switches—called transistors—that pump input strings of zeroes and ones through a series of logical operations to produce an output string of zeroes and ones, which represents the answer.A logical operation is a rule for manipulating the binary values. Each operation takes an input of either one or two bits, and produces a single output bit whose value is deter-

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the classical transistor could encode a single 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 consequence of the principle means that it can be both red and blue simultaneously! 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 macroscopic world; this qualitatively new unit of information in which both zero and one coexist in a superposition is called the ‘quantum bit’, or ‘qubit’ for short. It becomes apparent that a system composed of two atoms, i.e. two qubits, allows us to encode four possible numbers (represented by zero-zero, one-one, zero-one, one-zero) at the same time, compared to only two for the classical system with two transistors. With three qubits we have nine numbers stored simultaneously compared to three classically, with four qubits we have 16 numbers and with 300 qubits we have as many numbers as there are atoms in the universe! The memory of a quantum computer increases much faster than that of its classical counterpart. The rule is that N qubits, or atoms in the system, encode 2N numbers. In other words, owing to the in-built ability to store and process information ‘in parallel’, a quantum computer can perform a calculation in a single step, while a classical computer needs many more. The unusually named ‘Blue Mountain’ and ‘ASCI Q’ are the world’s two most powerful classical supercomputers, based at the Los Alamos Laboratories in the United States, where they simulate nuclear explosions. As astounding as it may sound, a quantum computer consisting of only 13 atoms could outclass Blue Mountain. Quantum computers are much more than yet another benchmark of speed and memory. A more profound reason as to why they are a new kind of device is that they are fundamentally different in the way they perform logical operations. Classical computers use classical algorithms—each a series of logical operations. For quantum computers, we would have to devise unique quantum algorithms, which have no classical counterpart for they would have to take account of the qubits which have the value zero and one at the same time. Quantum algorithms may one day find applications in the field of code cracking. When you are sending your credit card

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Quantum computers are much more than another benchmark of speed and memory

details over the internet, say, the information you are transmitting is jumbled by an encryption key, known only to the recipient. The key is a very long number obtained by multiplying two smaller numbers, which allows the recipient to reverse the jumble into useful information. In modern cryptographic codes, cracking the key involves factorising the very long number, i.e. decomposing it into the smaller numbers that were originally multiplied to obtain it. Any eavesdropper would have to be very determined to crack the code as factorising long numbers is an extremely hard problem, even for computers. When we multiply or divide two numbers, we resort mechanically to a set of rules called an algorithm. As the numbers we are multiplying grow bigger, the time needed to perform the operation grows longer, but not that much longer, because the multiplication algorithm is efficient. The increase in difficulty is said to be ‘polynomial’.The problem with factorising is that we know of no efficient rule for the operation so with each extra digit added to the number being factorised, the time required for each operation increases exponentially. The problem is exponentially hard. Classical computers struggle with factorisation due to the algorithms they use to solve it. This weakness is exploited by modern cryptographic codes, which rely on the inability of an eavesdropper to easily factorise numbers over 150 digits long—a problem that would stretch even the most powerful computers and could take many months to complete. In 1994 Peter Shor, a researcher at the Bell laboratories, came up with a quantum algorithm—a new set of rules—to factorise large numbers in about the same time it would take a classical machine to run simple multiplications or divisions.To highlight the fundamental difference between quantum and classical algorithms, a quantum computer with atoms flipping state at a rate of one each second—an eternity by the standards of even humble desktops—could still produce an answer to a problem like factorisation in

Information has to be encoded in a physical host, meaning that it is subject to physical laws

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a fraction of the time it would take the most powerful classical machines. Writing new quantum algorithms is complicated because devising these rules requires the invention of new logical operations that take into account the superpositions of many states, rather than individual bits. And, since the output of a quantum computer is also a superposition of all the possible answers, an additional challenge is to ensure that the ‘correct’ answer is picked from that output. Nobody knows what form a working quantum computer might take. Some argue that the difficulties facing pioneers are so phenomenal that a working quantum machine that rivals desktops is wishful thinking. Challenges facing researchers include the preparation of qubits, the read-out of output qubits and the devising of quantum algorithms. One of the more intimidating problems to be solved is how to cope with the extreme fragility of the state superposition that form the qubits. Unless a qubit is extremely well separated from interactions with the outside environment, it collapses into a single state and dissipates information in a process known as ‘decoherence’. As the number of qubits increases, it becomes harder to keep the system safe from decoherence effects. These difficulties have not deterred enterprising researchers. A number of groups around the world are already testing embryonic working quantum devices. In 2001, Isaac Chuang and his team at IBM successfully factorised the number 15 using a seven-qubit quantum computer running Shor’s quantum algorithm. The device consisted of a liquid which contained five fluorine atoms and two carbon atoms, which were encoded using radio pulses tuned by nuclear magnetic resonance. The scope for using the Shor algorithm for code breaking has not gone unnoticed by governments, who became interested and immediately increased funding. Whether or not code breaking computers are built, however, potential applications of quantum computers are vast.Whilst classical computers struggle to predict the weather, quantum machines could excel at simulating the 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. Tristan Farrow is a PhD student at the Cavendish Laboratory

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DNA Damage and Repair Zoe Smeaton highlights a Cambridge scientist s efforts to revolutionize cancer treatment DNA damage, caused by external agents such as UV radiation and smoking, or by oxygen radical byproducts of intracellular metabolism, has serious consequences if left unrepaired. Normally cells employ a host of DNA repair pathways to correct damage, but when these systems fail, a range of disorders may ensue including cancer, premature ageing and infertility. Recent research into DNA repair pathways in humans suggests that these pathways can be successfully targeted by therapeutics used to treat several of these conditions. According to Professor Steve Jackson, who works on DNA damage and repair systems at the Gurdon Institute in Cambridge: “Most people are aware of the fact that exposure to too much DNA damage can lead to cancer, and for me, research into the DNA damage and repair pathways has more to offer oncology than almost any other field.” Professor Jackson has set up Kudos Pharmaceuticals Limited, a company which has developed several drugs that could potentially revolutionize cancer treatment by exploiting the sensitivity of

cancer cells to DNA damage.This sensitivity arises from the rapid division of cancer cells in comparison to normal cells, which leaves little time for DNA repair to take place. Additionally, cancer cells often have impaired DNA repair pathways making them more reliant on remaining functional back up systems that can also repair DNA. This sensitivity to DNA damage is already exploited widely by radiotherapy and most chemotherapies, which cause double-stranded breaks to form in DNA. Unlike normal cells, tumour cells cannot repair these breaks, so die in response to treatment. Some drugs specifically target tumour cells with mutations in their DNA repair systems. These drugs were first developed by Professor Leland Hartwell— winner of the 2001 Nobel Prize in Physiology or Medicine—and his colleague Dr Stephen Friend. Using yeast cells that contained genetic mutations characteristic of specific tumours, they set up a drug discovery program to identify drugs and their targets that would have practical applications in the treatment of tumour cells.

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Recent research into DNA damage repair pathways has lead to the development of drugs that increase the effectiveness of radiotherapy by further hindering 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 pathway 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 backup 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 targets BRCA 1 and 2 deficient tumour cells and renders them more susceptible than normal cells to the DNA damage induced by radiotherapy. Jackson adds that whilst this drug can be used to increase the efficiency of radiotherapy by making the tumour cells less able to cope with DNA damage, researchers are finding that “the PARP inhibitor on its own is killing the cells without any extra damage from radiotherapy—probably because there is a lot of DNA damage going on in cells all the time anyway.” Whilst the PARP-inhibitor can only be used to treat cancers which are BRCA 1 and 2 deficient, Jackson thinks that as we begin to better understand the changes that occur in cancer cells, molecular targeting of tumours will become more useful: “If we can understand the differences between the cancerous and the normal cells, then it is my belief that in the end we should be able to come up with drugs to specifically target every different kind of cancer.” The range of diseases potentially affected by impaired DNA damage repair systems is vast, providing a number of potential applications for this area of research. For instance, studies have suggested that inhibition of PARP activity—in addition to helping treat BRCA deficient cancers—could reduce heart damage occurring during a heart attack by up to 40%, and neuronal damage caused by a stroke by 85–90%.The study of DNA repair pathways has much to offer in the world of medicine, and it is expected that this relatively new area of research will yield many effective therapies in the future. Zoe Smeaton is a third year Natural Scientist specializing in Cell and Developmental Biology

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Human use of chocolate dates as far back as the Pre-classic period (900 BC to AD 250). Using high performance liquid chromatography, scientists discovered cocoa residues in Mayan ceramic pots used in food preparation, dated around 600 BC. Numerous Mayan murals and ceramics are inscribed with hieroglyphs depicting chocolate poured for rulers and gods. Perhaps this is not surprising, considering that the latin name for the cacao tree, Theobroma cacao, means ‘food of the gods’.

the neurotransmitter that can produce feelings of ecstasy. However, tryptophan is present in chocolate in only small quantities fuelling debate as to whether it causes elevated production of serotonin. Phenylethylalanine, which promotes feelings of attraction, excitement, giddiness, and apprehension, has also been isolated in chocolate, but again, its low concentration may be insufficient to produce the effects typically associated with this compound. Threobromine—a weak stimulant found in chocolate—in concert with other

Perhaps the best compromise is to snack in moderation, particularly on dark chocolate. Not only does it contain more cocoa and proportionally less sugar and fat than milk chocolate, but it is also full of antioxidants, called flavonoids. In fact, dark chocolate has been reported to contain more flavonoids than other antioxidant-rich foodstuff, such as red wine. Flavonoids reportedly prevent cancers, protect blood vessels, promote cardiac health, and counteract mild hypertension (high blood pressure).

Dhara Thakerar explains the science of chocolate When chocolate was introduced to Europe in the sixteenth century by the Spanish conquistadors, a sweetened version became a luxury item throughout the continent. In 1847, the first commercial chocolate bars were invented in England by Joseph Storrs Fry, with the Cadbury brothers following shortly after.

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Cocoa butter may protect teeth by preventing plaque formation

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Ever since, chocolate has been absorbed into the fabric of daily life; however, few are familiar with the ways in which it affects our body. The media’s message about chocolate remains confusing, as reports alternate between scrutinising chocolate for health risks and praising it for hidden health benefits. So, is the mantra of ‘eating just a piece a day’ more detrimental than beneficial? The pleasurable feelings chocolate induces can be explained by its physical properties. Professor John Harwood and his colleagues at Cardiff University believe that the high stearate content of cocoa butter, a key ingredient in chocolate, is responsible for its melting behaviour and stability. Cocoa butter contains between 30% and 37% stearate in its lipid content.As a result, it is solid at room temperature, but when consumed, its fat content absorbs heat from the mouth and melts at body temperature, producing the ‘melt in the mouth’ effect. Chocolate has long been suspected of aphrodisiac properties: the Aztecs thought it invigorated men and made women uninhibited. Consistent with this, the chemical tryptophan is found in chocolate. This is used in the brain to make serotonin;

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chemicals such as caffeine, may be responsible for the characteristic ‘buzz’ experienced when eating chocolate. Scientists at the Neurosciences Institute in San Diego suggest that chocolate contains pharmacologically active substances that produce a cannabis-like effect on the brain, such as anandamide: a cannabinoid neurotransmitter. Chocolate also contains Noleoylethanolamine and Nlinoleoylethanolamine. These chemicals inhibit the breakdown of anandamide, and thus may prolong its effects. In addition, elevated levels of the neurotransmitter can intensify the sensory properties of chocolate (texture and smell), thought to be essential in inducing cravings. The high fat content of most chocolate—Cadbury’s Dairy Milk alone contains 30 g of fat per 100 g—means that excesses can contribute to obesity, which carries with it a range of health risks, including heart disease and diabetes. Nevertheless, not all accusations levelled at chocolate can be justified. The often-touted link between chocolate and acne has been intensively studied for three decades. In a 1969 study at the University of Pennsylvania School of Medicine, 65 subjects with moderate acne ate either chocolate bars containing 10 times the amount of chocolate found in a typical bar or identical bars containing no chocolate.Test subjects who consumed the excessive amount of chocolate for four weeks did not show signs of increased acne. Additionally, chocolate has not been proven to contribute to cavities or tooth decay. Cocoa butter may in fact coat teeth and help protect them by preventing plaque formation. While the sugar in chocolate contributes to cavities, it does so no more than the sugar in other sweet foods. However, by altering blood flow to the brain and releasing norepinephrine, some chemicals in chocolate can cause migraines.

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Chocolate s Chemical Charm Milk chocolate may not offer the same benefits. In one study, patients on separate days ate 100 grams of dark chocolate, 100 grams of dark chocolate with a small glass (200 ml) of whole milk, or 200 grams of milk chocolate. One hour later, those who ate dark chocolate alone had the highest concentration of antioxidants in their blood, suggesting that the milk in milk chocolate may interfere with the absorption of antioxidants.

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Chocolate contains substances that produce a cannabislike effect on the brain

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Science can explain a number of features that contribute to the lasting popularity of chocolate, although how some of the effects we experience post-consumption occur is still debatable.Whilst it is unlikely to ever be marketed as a health product, eating the darker varieties and snacking in moderation could prove beneficial. But, one thing is certain: from perspectives both scientific and sensory, there is nothing else quite like chocolate. www.bbc.co.uk/science/hottopics/chocolate Hurst,W. J. et al.,Archaeology: Cacao usage by the earliest Maya Civilization, Nature 418: 289–290 (2002) Serafini, M. et al., Plasma antioxidants from chocolate, Nature 424: 1013 (2003) Dhara Thakerar is a second year Natural Scientist

All images courtesy of www.nasa.gov

Are We Really Alone? Gemma Simpson explores the universe for possible signs of life From ET to the Clangers, there is no escaping our fascination with the idea that aliens exist. But after years of speculation and searching, nobody yet has confirmed an extraterrestrial sighting. This might seem like a problem when establishing a science like astrobiology, the study of life outside the Earth. As an emerging field, astrobiology combines aspects of astronomy, biology and geology in the search for extraterrestrial life. ‘Life’ could be anything from a single celled amoeba to a complex organism, and it could be found within the planets and moons of our own solar system or on a distant planet orbiting another star. Although scientists are enthusiastic about the range of questions involved, astrobiology is often criticised by the general scientific community for its speculative nature. So far, no one has come ‘face-to-face’ with an alien, but there are several indirect indications which suggest that life might be present elsewhere in the universe. When looking at other stars, astronomers have found planets. Encouragingly, these exoplanets (planets outside our solar system) are proving to be quite common. Over the past ten years, 160 exoplanets have been found, but these planets are gas giants—similar to Jupiter—making them 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 exist, and new technologies for finding them are being developed. You may remember that in 2004 Venus could be viewed from Earth as it crossed in

front of the Sun (a process know as a transit). Similarly, when an exoplanet crosses in front of a star it will block out some of the star’s light. Using this characteristic dimming, two projects have been planned to look for habitable planets that can maintain liquid water. A French probe called COROT is due for launch in July 2006 and the NASA telescope, Kepler, is planned for launch in June 2008. Even if these missions find an Earthlike planet that has liquid water, there is no guarantee that life will exist there. There are certain indicators to look for when detecting life on other planets. One such indicator is the presence of oxygen. Two space-based telescopes, NASA’s

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No one has yet come face-to-face with an alien, but there are several indirect indications to suggest that life might be present elsewhere in the universe

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Terrestrial Planet Finder and ESA’s Darwin, are being designed to look for oxygen around other planets and moons. However, oxygen alone does not indicate life as non-biological processes can also produce oxygen.

It is possible that the planets or moons in our solar system could support some simple form of life. Mars has always been the front-runner in the search for extraterrestrial life. In the 1970s, soil samples from NASA’s Viking Mars mission were found to contain methane. It is thought that sunlight would take approximately 300 years to destroy methane molecules in Mars’s atmosphere. Therefore, the presence of methane suggests that it is being actively replenished, possibly by living organisms. However, other experiments failed to find evidence of methane and the results were declared to be a false positive. The Mars Express and NASA rovers recently found two key pieces of evidence that suggest life could exist on Mars. 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 concentrations of sulphur and chlorine, suggesting that these minerals were repeatedly leached out and re-deposited by water. More convincingly, mysterious ‘spherules’ (tiny spheres) were found. Spherules are thought to be built up layer by layer in liquid water, just like pearls in the ocean. However, it remains to be discovered if they were created by water or if they were 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 present on Mars there may still be traces beneath the Martian surface and thus the coexistence of life is a possibility. Secondly, instruments on the Mars Express orbiter

detected methane in the atmosphere. Further analysis is needed to pinpoint where the methane is originating, as subsurface volcanism, rather than life, could account for the gas. Mars is not the only possible host for extraterrestrial life in our solar system. There is potential for life to exist on Saturn’s system of rings and moons. Saturn’s moon Titan is of particular interest due to its resemblance to Earth. NASA’s Cassini spacecraft entered orbit with Saturn on 30 June 2004 and immediately began sending back intriguing data and images. ESA’s Huygens Probe hitched a ride on Cassini and descended into Titan’s thick atmosphere in January 2005. On its descent to Titan, Huygens sent back images of channels and gullies that looked very similar to the liquid-cut features seen on Earth. However, the liquid observed is most likely to have been liquid methane and not water. Furthermore, two teams of astronomers found short-lived clouds of methane on Titan which lasted between several hours and a day. Whether or not these clouds of methane were produced by microbes is unclear. Huygens also revealed a possible ice volcano on Titan so geological activity could have produced the methane clouds. Other signs of life have been observed within Venus’ clouds and on the icy surface of Jupiter’s moon Europa. Data from the Venus probes and landers gave ‘chemical hints’ that microbes could exist in the clouds above Venus. In addition, a red tinge was observed on the surface of Europa. No one has yet been able to explain what

combination of compounds could have created this red tinge. However, there have been suggestions that it could have been created by frozen bacteria such as Deinococcus radiodurans and Sulfolobus shibatae which happen to be pink and brown. In 2003, sulphur traces on Europa were hypothesized to be a sign of alien life.The sulphur traces look similar to the waste products of bacteria that get locked into the surface ice of lakes in Antarctica. Unfortunately, there is no way to check the data without a trip to Europa’s surface. One of the fundamental questions astrobiology aims to answer is how life began on Earth. One possible explanation for life on Earth and other planets is the interplanetary transfer of microbes, facilitated by meteorites; meteorites from Mars frequently hit Earth. It is believed that, if there were organisms on these meteorites, they would be resilient enough to survive the harsh journey through space before colliding with Earth. It has been suggested that Mars may have had a habitable environment before Earth.Therefore, the possibility exists that we might have descended from microbes that came to Earth on a Martian meteorite! In 1996, NASA scientists controversially announced that they had found fossilised microbes in a lump of Martian rock (ALH84001) discovered in Antarctica. Careful analysis revealed that the rock contained organic molecules and tiny amounts of the mineral magnetite, often found in Earth bacteria. However, the evidence was insufficient to conclude that this was indeed a Martian fossil. The discovery of alien microbes would be an outstanding achievement for science, but what about intelligent life? Could intelligent extraterrestrials already be trying to contact us? The Search for Extraterrestrial Intelligence (SETI) uses highly sensitive radio-telescopes to search for broadcast messages. In 2004, the SETI project received a puzzling radio signal three times from the same region of space. This signal is widely thought to be the best candidate yet for alien contact; the catch being that it came from a region in space where there are no obvious stars or planets. It may be that the signal is simply from a yet unknown physical phenomenon. If aliens are trying to establish contact, they will probably be using a method more sophisticated than radio waves. Lasers are a possibility as they hold more information than a radio wave and are less prone to interference allowing a better quality signal to travel longer distances. Optical SETI is another branch of the search for alien life.They use groundbased telescopes to look for alien laser signals hitting Earth. Maybe an alien message is staring us straight in the face,

stored in some durable artefact on Earth like the pyramids. It is also a possibility that Earth’s radio signals could be picked up by intelligent alien life. An advanced life-form could potentially have picked up even the weak early radio signals transmitted from Earth. As we have only been transmitting radio waves since the early twentieth century our signals will not yet have reached more than 100 light years away. However, within a 100 light year radius, there are many thousands of stars which could host intel-

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Recently, the Mars Express and NASA rovers found two key pieces of evidence that suggest life could exist on Mars

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ligent life. Media services are increasingly being delivered by technologies that do not leak radio signals. Therefore, if any intelligent aliens are trying to look for us using radio waves, they might not have long before Earth ‘disappears’. As an emerging scientific field, astrobiology has struggled to gain respect within the scientific community. There are concerns that astrobiology is not distinct enough from its parent disciplines to be a true science. It is widely held that astrobiology is too much of a speculative extrapolation of Earth conditions into nonEarth environments. A more serious criticism is that extrapolating from a single data source is extremely unscientific. The characterization of extraterrestrial life is unresolved; theories as to its existence vary and true astrobiological experiments simply cannot occur at this time (with minor exceptions such as the ALH84001 meteorite found in Antarctica). Even if civilisations are common in the galaxy then you hit the Fermi Paradox that can be summarised as:‘The belief that the universe has many advanced civilizations, combined with our observations that suggest otherwise, is paradoxical, suggesting that either our understanding or our observations are flawed or incomplete.’ So, where are they? Have they already arrived on Earth and we just don’t know about it? Would they prefer not to communicate with us? Or, are we simply missing their signals? It could be that intelligent life has yet to form in the universe. Maybe we really are alone. Gemma Simpson is a PhD student in the 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 ago that people would be willingly and deliberately consuming products containing bacteria? Yet in recent years foodstuffs containing ‘friendly bacteria’ or probiotics such as yoghurt drinks have become widely available. Countries such as Finland and Sweden have been actively using probiotic products for several decades. However, many scientists remain sceptical about their benefits. So what exactly does the scientific literature tell us about the real effects of these substances?

antimicrobial compounds—short peptides termed bacteriocins. There is no published data to show that probiotics are able to replace the body’s natural flora, only evidence that they form beneficial temporary colonies, which may perform the same function as the natural commensals. Thus, probiotic strains are never long-lived inside the body. On the plus side, there is now an increasing body of evidence to show that probiotics do have real benefits in treating or preventing certain diseases. These range from general claims such as a reduction in sick-days taken by adults or

have a beneficial effect “onProbiotics those who already have weakened immune systems The current theory is that by ingesting up to one billion cells of ‘good bacteria’, such as Lactobacillus acidophilus or Bifidobacterium bifidum, every day, the intestine is colonised where naturally occurring beneficial, or commensal, bacteria have been eliminated. This can occur through stress, taking antibiotics or oral contraceptives, or following a severe bout of diarrhoea. By adhering to the intestinal wall, these good bacteria prevent harmful bacteria from attaching to and over-colonising the gut, and thus maintain what is commonly referred to in advertisements as “a healthy intestinal flora”. The antimicrobial properties of probiotics are thought, in a large part, to be due to their reinforcement of the barrier function of the intestinal mucosa. In addition, some probiotics, such as Lactobacillus plantarum strains, secrete

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illnesses contracted by infants in day-care centres, to specific examples of prevention of diarrhoea whilst taking antibiotics, and reductions in the recurrence of yeast vaginal infections and irritable bowel syndrome. What is more, taking probiotics has no known side-effects, including a negligible risk that the friendly bacteria could enter the blood stream and cause infection. One of the most recent studies to be published on the benefits of probiotics involved a study of 181 factory workers in Sweden. Shift-workers are recognised to be at greater risk than day-time workers of contracting short-term illnesses, such as gastroenteritis or the common cold, and days off due to these causes can cost up to 2.2 billion euro per year in Sweden alone. In this study, each factory worker was given a daily dose of either

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108 cells of Lactobacilllus reuteri or a placebo in liquid form over a total of 80 days.This was a double blind trial, where neither the worker nor the administrator of the drink knew whether the dose contained bacteria or not. Of the daytime workers in this trial, 23 of 87 in the placebo group took sick leave compared to 10 of 94 in the L. reuteri group, statistically significant but not very impressive. By contrast, of the shift-workers studied, 33% of the placebo group took sick leave compared to none of the workers taking the active supplement. This suggests that probiotics have a noticeable effect in those who already have weakened immune systems. Importantly, both groups had been matched demographically: there were comparable numbers of males and females in each group and the mean age for both groups was the same. These new data are entirely in agreement with another Swedish study using the 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. Despite an increasing number of papers, such as those discussed above, there still remain many who are sceptical about probiotics. One of the arguments against purchasing probiotic products is that in the US, beneficial bacteria are considered to be a food supplement and not a pharmaceutical. This means that they do not have to be passed by the Food and Drug Administration (FDA), a key indicator of a product’s safety and clinical efficacy. This legally prevents a manufacturer from making clinical claims about the benefits of a product in the treatment of any given medical condition. Another downside, due to the supplement status of probiotics, is that the production and testing of probiotic foods is not strictly regulat-

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ed. What the manufacturer claims to be providing you on the outside of the packet may not strictly correspond to what is inside. A study conducted in Belgium on 55 different products specifically sold as probiotics found that only 13% of the products actually contained the bacteria listed on their labels, with more than a third containing no live bacteria at all! 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 because bacteria have a shelf-life, and the longer they are kept in a shop, the lower the count of viable bacteria in the product 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 through the stomach and small intestine, and so prevent them from colonising the intestine. In an effort to respond to these arguments and several others, it has been proposed that probiotics should pass a number of laboratory-based tests to establish their stability and efficacy.These include tests for acid stability, which have

already indicated that some strains of bifidobacteria can survive low pH better than others.This is likely to be an intrinsic characteristic of different strains of bacteria, and so is a simple way to rule out inappropriate sources of probiotics. Another important factor is that probiotic bacteria should adhere to the mucosal lining of the gut, as this has been correlated with reducing the duration of diar-

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There is now increasing data to back up claims that probiotics can be beneficial for a range of health conditions, especially in the young or immunocompromised. However, there is a lack of mechanistic data to explain exactly how probiotics act or whether certain bacteria may be more useful for preventing one illness than another—so not all probiotics may be as effective as each other.

The production and testing of probiotic foods is not strictly regulated

rhoea. This can also be tested in the lab using cultures of intestinal cells as model systems, although there is not currently one recommended cell line in use, as there have been differing results. Worryingly, observations have also been made that culturing the same strain of bacteria over a long period of time in an industrial environment may change its adhesion properties.

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The consumer needs to be aware of what they are purchasing; it is probably wise to buy products that are more likely to have been tested and standardised, and preferably those that have been trialled in studies with positive outcomes. Louise Woodley is a PhD student in the Department of Biochemistry

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The Sixth Sense Juliette McGregor uncovers the artwork we never knew we could see, Haidinger s brush Bees do it, fish do it and even plants do it, but few are aware that humans can do it too: detect the linear polarization of light with the naked eye. Surprisingly, our ‘sixth sense’ remains relatively obscure despite the abundance of sources of partially polarized light around us, ranging from the clear blue sky above to the liquid crystal displays (LCD) of laptops below.The difficulty of visualizing polarization and an incomplete understanding of its physical mechanism have contributed to the general lack of information regarding the phenomenon. But with a few tips and practice, you too will soon be able to see and understand the polarization of light. Most often called Haidinger’s brush, the image was first reported in 1844 by the Austrian mineralogist Wilhelm Haidinger. Since then, numerous literary and scientific 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 in the structures of the eye by describing it as, “something subjective, as it moves with the eyeball.” He was right; as an entoptic phenomenon, Haidinger’s brush is due in 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 light with the symmetrical, optically active elements of the retina. What does Haidinger’s brush look like? The image has been described as resembling a bow tie, hourglass, butterfly or brush (a mistranslation of the German ‘Büschel’ meaning ‘tuft’ or ‘stook’). To the trained eye, polarized light looks like a distant elongated yellow stain, pinched at the centre with yellow streaks subtending several degrees around a fixation point roughly the size of your thumb at arm’s length (Figure 1).The image is flanked by shorter bluish-purple regions that cross the yellow arms at 90°. The appearance of the brush varies from person to person because of

individual differences, like the thickness of the cornea. To see Haidinger’s brush, view a brightly illuminated white sheet of paper through a piece of Polaroid or the lens of a pair of polarized sunglasses. If you are having difficulty, try quickly rotating the Polaroid through a right angle.The image is easier to observe if it is moving because the change in polarization direction reinforces the new brush with the afterimage of the previous one. If you have a mobile phone, you can use its LCD to see polarized light. Firstly, adjust the phone to display a blank white screen, and then rotate it quickly by 90°. The LCD of a laptop would also work. Once you have learned how to recognise Haidinger’s brush, you should be able to see it even when looking at a stationary Polaroid.After a few seconds, the image will fade as your brain adapts and the eye fatigues, but it is visible long enough to catch a glimpse.With enough practice, you

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Our sixth sense is obscure despite the abundance of polarized light around us

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can observe Haidinger’s brush in the sky by slowly roving about its zenith after sunset on a clear day and tilting your head from side to side in the direction of the gaze. Explaining Haidinger’s brush requires an understanding of how polarized light interacts with the retina, a complex and unusual structure in the eye. Before reaching the photoreceptors, light is scattered as it passes through several neuronal layers. In the fovea—a region specialized for high acuity vision—this scattering is reduced by sweeping neurons and other structural elements radially outwards such that the light rays fall unimpeded onto the rod and cone cells. The displaced neuronal fibres form a radially symmetric region known as the macula lutea or ‘yellow spot’. Blue absorbing

Figure 1. Haidinger s brush

carotenoid pigments are associated with this fibre framework, and this structure is responsible for the phenomenon. Haidinger’s brush is believed to result from two distinct features of these fibres. Firstly, they are dichroic elements, so a change in the polarization angle produces a change in their transmission of light. In this case, more light is absorbed if the polarization direction is perpendicular to the fibres. Secondly, their arrangement in a radial or concentric pattern is thought to influence light transmission by preventing absorption from averaging out. White light depleted of blue appears yellow, accounting for the yellow bowtie shape that appears perpendicular to the plane of polarization.The blue regions are believed to be psychological in origin, produced as a contrast effect in response to the physical yellow. Clinical studies of Haidinger’s brush have proven difficult and the exact theory behind the visualization is yet to be verified. Recently, mathematical models of the eye’s optically active elements have been used to generate computer simulations mimicking the observed behaviour. These studies may make Haidinger’s brush useful as a medical diagnostic tool. Currently, the ability to see the image is used to diagnose various disorders of the eye, especially retinal damage. Problems visualizing Haidinger’s brushes may be an early indicator of eye disease, particularly age-related macular degeneration, the leading cause of blindness in the United Kingdom. Juliette McGregor is a fourth year Natural Scientist specializing in Physics

Strong blue absorbtion perpendicular to fibres

Incident Vertically polarised light

Macula lutea

Figure 2.When exposed to vertically polarized white light, the fibre arrangement favours blue absorption along horizontal meridian such that a yellow brush is perceived as shown.

Figure 3. The blue absorbing pigment molecules may be arranged radially or concentrically on the fibre framework, in either case the explanation holds.

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All images by Juliette McGregor

Weak blue absorbtion parallel to fibres

Chi Ngai Chan examines the link between grapefruit juice and Viagra To most people, grapefruit juice is a natural product that supermarkets sell by the litre and people consume daily with their breakfast. However, research has shown that grapefruit juice can interact with mechanisms used by the human body to eliminate foreign chemicals. Consequently, this can affect the way the body deals with drugs such as Viagra, a drug prescribed for erectile dysfunction, and terfenadine, an anti-histamine used to combat hay fever. Our bodies are capable of metabolising foreign chemicals: a natural defence mechanism developed to detoxify substances such as toxins in poisonous plants. When you take a drug it does not stay in your system forever. Any substance that the body 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, which are then excreted in urine. These reactions are divided into phase I and phase II, the former generally involving the break-up of the drug mol-

ecule, for example hydrolysis or deamination, while phase II reactions normally involve addition of chemical groups to the phase I derivative. Not all drugs are metabolised; some, such as the antibiotic gentamicin, can be excreted from the body chemically unchanged. Incredibly, drug metabolism can activate drugs converting them from their inactive state, known as a pro-drug, to the active form of the drug.An example of this is the pro-drug enalapril which only inhibits its target once hydrolysed to enalaprilat, an antihypertensive agent (a drug which lowers blood pressure). So where does grapefruit juice fit into all of this? About 15 years ago a study used

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grapefruit juice to mask the taste of ethanol in an investigation examining ethanol’s effects on the drug felodipine (an antihypertensive agent). In this study, the blood concentrations of felodipine were much higher than those observed previously. Analysis of the possible causes of the high felodipine levels found that grapefruit juice

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Drinking grapefruit juice can increase the blood concentration of sildenafil citrate (Viagra) after it is administered

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was the culprit, it was affecting the way in which felodipine was metabolised in the body! It is now known that certain constituents of grapefruit juice inhibit enzymes involved in phase I reactions. These enzymes are part of a large family called cytochrome P450. The mechanism by which they work involves a complex cycle of reactions called the monooxygenase P450 cycle. Interfering with this metabolic process, as grapefruit juice does, has been shown to have major effects upon the action of certain drugs in the body. The most important inhibitory component in grapefruit juice

has been identified as 6’,7’-dihydroxybergamottin which inhibits an isoenzyme of P450: CYP3A4. It has been suggested that 6’,7’-dihydroxybergamottin may also decreases the expression of CYP3A4. If there are fewer enzyme molecules present, the rate at which a drug is broken down will decrease, resulting in higher blood concentrations of that drug. One drug metabolised by CYP3A4 is Viagra (sildenafil citrate) which is broken down to desmethyl sildenafil, a compound that is pharmacologically much less potent.

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Sasha Krol

Citrus Paradisi Initial evidence suggests that drinking grapefruit juice can increase the blood concentration of sildenafil citrate after it is administered due to the inhibition of CYP3A4. Current research implies that the increase is unlikely to potentiate either the therapeutic or adverse effects of sildenafil citrate. On the other hand, considering that certain side effects of sidenafil citrate, such as hypotension (a decrease in blood pressure) may become more prominent, especially if being used concurrently with an antihypertensive agent, avoiding grapefruit juice would be a sensible precaution. The effects of grapefruit juice can be extremely serious, a scenario best illustrated by the tale of the antihistamine drug terfenadine. Histamine is an important mediator in allergic reactions, causing symptoms such as itchiness and reddening of the skin, conditions familiar to hay fever sufferers. Antihistamines, like terfenadine, block the receptors for histamine, thereby preventing its effects and relieving allergic symptoms. The problem is that terfenadine is a prodrug and must be metabolised to the active product, fexofenadine, by P450. However, when P450 is inhibited, terfenadine builds up in the body and interacts with a potassium channel in the heart encoded by the HERG gene.This can disrupt normal functioning of the heart resulting in cardiac arrhythmia. Unfortunately, deaths occurred before this serious side-effect was discovered. In 1998 terfenadine was withdrawn from the market in the US and Canada 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 juices such as cranberry juice have been shown to have similar effects, but grapefruit juice is certainly one of the better characterized. So, next time you drink a glass of grapefruit juice take a minute to think about the chemicals contained within, and the startling effects they can have upon your body! Chi Ngai Chan is a second year Natural Scientist Under normal circumstances, grapefruit juice does not harm the body. However, you should discuss possible drug interactions with your doctor or pharmacist.

On the Cover

Small Fields of View

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Electron holography measures the magnitude and direction of magnetic fields

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allows not only the amplitude of an electron to be measured as in other electron microscopes, but also the electron’s phase. In a specialised TEM, a highly coherent source of electrons creates an electron beam that is split in two by a biprism. When the two beams are recombined, the resulting interference pattern is dependent on their relative phases, which can thus be measured from the interference pattern with high accuracy. Electron holography was one of the first ways of verifying the physical reality of the magnetic vector potential. Only now, achieved by a handful of groups in the world including HREM at Cambridge, can magnetic fields be resolved down to nanometre length scales. Currently Simpson focuses mainly on examining magnetotactic bacteria, working with, among others, a research group in Hungary.These fairly common bacteria grow magnetite crystals along chains in their bodies which they use to navigate in the geomagnetic field, for example to move up and down a water column while seeking a feeding site. Simpson studies the magnetic microstructure and magnetic interaction

of these chains. The magnetic moment produced by such a chain is directly proportional to its length, and it is found that the bacterium will grow a chain to the particular length that optimises its magnetic moment. He also works with a group at Bremen University, who focus on the genetic control of the chain growth.Their genetic engineering experiments have produced bacteria with different morphologies of the chains, including two-dimensional arrays of the magnetic crystals. Simpson has found that the crystals in the arrays interact magnetically with each other in much more complex ways than the linear chains. These small scale biosystems are important models that show how the magnetic interactions of 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 due to the fact that the more a crystal is reduced in size, the more likely it is to be superparamagnetic (having no stable magnetic moment). Embedding the particles in a matrix as in other natural systems, such as in rocks, allows magnetic properties at a much smaller volume. The cover image is taken from Simpson’s work with the Department of Engineering at Cambridge. The department grows nanotubes using a cobalt/palladium catalyst for a variety of purposes. Incidentally the catalyst, which is embedded in the end of the tube, is magnetic. Simpson characterises the magnetic properties of the tubes. These tubes may form the building blocks of future hi-tech components: the magnetic particles at the end of the tube will affect the spin of an electron that is passed through the tube, a phenomenon that can be applied in spintronics, a branch of electronics in which the spin property of electrons is exploited for information storage. The cover shows two of the nanotubes with magnetic crystals at their ends interacting with

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each other through the fields they induce. The field lines are digitally overlaid, as are the colours which have been determined from the direction and intensity of the magnetic field. One of Simpson’s smaller projects includes the iron-carrying protein, ferritin. The iron carried by this protein in most of its forms is not magnetic. Simpson is investigating the iron in people with the condition haemochromatosis in which too much iron is produced. Another project is the characterization of damaged brain cells in Alzheimer’s patients. This disease is thought to be associated with an increase in iron in the brain. Simpson examines amyloid plaques from the brains of sufferers to determine if they contain iron in a different form. In studies of complex microstructures such as cells and proteins, electron tomography images are often usefully compared with electron holograms, to combine three-dimensional visualization of the physical structure with the magnetic structure. In his current work, Simpson uses the apparatus at its very limits. Over the past six years, the HREM group has developed electron holography to a new level of spatial (approximately 10 nanometres) and magnetic (approximately millitesla) resolution. Alongside his contribution to various fields of research, Simpson is working to further increase the microscope’s resolution and the sophistication of its quantitative processing. Victoria Leung is a third year Natural Scientist specializing in Physics

Ed Simpson

The Department of Materials Science and Metallurgy’s High-Resolution Electron Microscopy (HREM) group occupies a section of the old Cavendish Laboratory on Free School Lane. Inside, in what was once the physicist James Clerk Maxwell’s clock room, PhD student Ed Simpson uses a Transmission Electron Microscope (TEM) to perform electron holography, a technique that images magnetic and electrostatic fields. Using this technique, Simpson studies a surprising diversity of nanomagnetic systems, which he does in collaboration with colleagues from Europe and the US. Electron holography, a TEM imaging technique that can measure the magnitude and direction of magnetic fields, was first proposed in the 1940s and has been greatly developed since the 1970s. The Aharonov-Bohm effect—when an electron passes through a region of non-zero magnetic potential, the quantum mechanical phase of the electron is altered—forms the underlying principle of this technique. The important point about electron holography is that it

Abinand Rangesh

Victoria Leung interviews Ed Simpson, the scientist behind our cover image

Magnetite Crystals. Induction map of the magnetic field of two double chains of magnetite nanocrystals taken from magnetotactic bacterium.The map was created from an electron hologram in the TEM, and colours are derived from the direction and intensity of the field, with field lines overlaid. Each crystal is approximately 50—70 nm.

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A D ay i n t h e L i f e o f …

A Defence Scientist In recent years, national security and defence have received increasing attention, both in government agendas 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 worldleading 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 sector. The Public Private Partnership arrangement that exists at the company today allows QinetiQ access to over 50 years of technological experience in projects from liquid crystal displays to advanced robotics. When did you begin working at QinetiQ and how did you get the job? I first began working for the Royal Radar Establishment (RRE) in 1974. It went through numerous transitions to become DERA and finally QinetiQ. Each transition was marked by a merger of several locations and a broadening of expertise and responsibilities. Having read Electrical and Electronic Engineering at UMIST, I had a post-university job painting everything white for the Army on Salisbury plain (simple instructions—if it moves, salute it; if not, paint it) when a friend at RRE said “Come and work here—all I do is walk up and down a runway, swinging my arms and pretending to be a man. Even you could do that!” He was being a target for portable radar to train operators to distinguish between different activities, such as marching or sneaking around, using the different swishing noises produced by the radar. Naturally, I applied for a similar job but was posted to the Metrology (the study of systems of measurement) Department instead. Did you have any previous experience in the field? No. I had done work experience as a dustman and was looking for anything that did not involve rotten banana skins sliding down my neck! My current job title is RF Stealth Expert Group Leader, and this combines my previous experience as a metrologist, working on Microwave National Standards for the National Physical Laboratory, with electromagnetic experience I gained from the Radar Department. What does your typical work day involve? The team that I lead has a wide range

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QinetiQ

Louise Woodley speaks to Jezz Ide about his work at QinetiQ

of skills covering electromagnetic prediction and measurement, including physics, chemistry, and mechanics.A typical day can include discussions with customers on current or future work, planning the development of new computer codes that will predict the interactions of electromagnetic fields and solid bodies such as planes and tanks more efficiently, and designing more costeffective ways of validating computer predictions using physical models. In the same day I can, therefore, alternate between thinking or staring at a computer screen and mediating or contributing to meetings. Having worked at QinetiQ as it made the transition from a government body to a commercial venture, has the nature of your work changed significantly? The nature of the work has changed more in response to the changing nature of the MoD, our part-owner and major customer. Since the Strategic Defence Review and the introduction of Smart Procurement (a procedure aimed at massively reducing the delays in major programmes) the emphasis has changed from the delivery of research to the delivery of capability. For QinetiQ, which started as a research organisation rather than a manufacturer, the challenge has been to convert technical expertise into commercial products. Are there any projects that you have been involved in that stand out in your memory as being particularly interesting or exciting? The most interesting project I have been involved in from the personal viewpoint was an International Comparison of Microwave Power. This gave me a technical and intellectual challenge and enabled me to interact with international peers. Metrology and standards underpin all trade but are largely taken for granted; the drivers for many technical improvements in metrology come from trade disputes, as how big you want a gallon of petrol to be depends on whether you are buying or selling.

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Have you ever had any ethical concerns about projects you have been asked to work on? Are employees able to decline working on specific projects? The advantage of working for a large organisation with broad research interests is that people can generally be matched to an area in harmony with their beliefs. If you are a specialist in a particularly limited field, this may be more difficult. However, many areas can have civilian applications, for example, in Stealth understanding how radar interacts with turbine blades can be used to predict the effect of a wind farm on airport radar. Due to the confidential nature of the research, do you get much opportunity to discuss ideas with other scientists from other institutions or companies? The MoD generally prefers to place large projects with consortia rather than individual companies. They hope to achieve a mix of skills from the unchained thoughts of academia to the ‘oil and sawdust’ of manufacture. In these circumstances it is necessary to communicate with your partners just enough to ensure the success of the project, but not so much that they could succeed without you.This is made more difficult by shifting alliances, where a collaborator for one project may be a competitor on another. What is the best aspect of your job? The technological challenges never go away: there is always faster, bigger, better to aim for.What is more, there is a beneficial spiral whereby improvements in prediction capability are confirmed by measurements, leading to a better understanding of some interactions, which the leads to an improvement in the prediction capability, and so on. What is the worst aspect of your job? People assuming that because I’m an expert in microwaves, I can fix their kitchen appliances. Louise Woodley is a PhD student in the Department of Biochemistry

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 components. I had modelled what happens as these gases cool, what happens as they dilute, and even what happens when they start to mix with atmospheric oxygen. But something was missing in all of this… In September 2005 I flew to Sicily with a group of Cambridge volcanologists 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 sampling the gases and particles released from open vents on the summit of Etna, which is currently about 3330 metres above sea level—the summit height varies, but fortunately it didn’t during our stay! From our base camp at a Sicilian B&B, Etna was clearly visible, with its plume of volcanic gas drifting away to sea. The trip to the summit involved a sturdy-looking 4x4, and roads that quickly became dirt tracks as the scenery changed from forests to impressive lavaflows carpeting the landscape. There was no ‘are we nearly there yet?’ about this particular journey. For the final push we had to leave the 4x4s behind and walk, carrying all our equipment with us. As we climbed the last hundred metres or so, I really wasn’t sure what to expect but, with the occasional waft of nasalburning acidic fumes, it started to hit home that the day ahead was probably 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 mask and sunglasses, we approached the north-east crater (one of the four main vents on Etna) for the first time. Peering

Mount Etna from a distance

All images by Rob Martin

Away from the Bench

Volcanic Chemistry

Rob Martin on the slopes of Mount Etna

over the edge of the crater, it became evident that on one side of us was a gaping volcanic vent pouring out hot gases, while on the other was a large fall down the side of the mountain! Most of the time the gases emerging through the vent on the crater floor obscured the bottom, but every now and then the wind cleared the gases from the crater, revealing the vent itself. Fear of death aside, I set about doing some science. Acidic gases (HCl, HF, H2SO4) were collected on alkali-soaked filters. Filters were also used to collect larger volcanic aerosols (more than one micrometre), which are often made up of several over-grown phases (such as silicates, chlorides, fluorides and sulphates), as well as mechanically generated dusts, and volcanic glasses thrown from the magma. Another instrument was used to collect the smaller volcanic aerosols (less than one micrometre). Once the instruments were up and running we finally had time to stop and take it all in. In addition to the main open vents, the summit was dotted with many fumaroles (smaller vents through which gases escape) covered with vividly coloured encrustations of yellow, orange and white crystals.The noise at the summit was similar to a kettle boiling; the whistling rush of hot gases accompanied the ever-present drone of our equipment. Lunch consisted of a well-timed removal of the gas mask, a quick mouthful of food, followed by a speedy replacement of the mask to avoid inhaling a lungful of volcanic gas. Mid-afternoon, the clouds set in and so after several hours of sampling we

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made our way back down to the B&B. That evening the instruments were prepared for the following day, and the samples were safely stored for analysis back in the UK. Such was our routine for the rest of the week. The data we collected will be used to further our understanding of the chemistry of volcanic plumes, and probe the mechanisms by which volcanic aerosols form and grow as the volcanic plume cools.

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The scenery changed from forests to impressive lava-flows carpeting the landscape

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Each day on Etna was memorable in a very different way. The weather ranged from T-shirt weather to the sort of weather that demands five layers and thick waterproofs as well as gloves. Visibility ranged from being able to see across to the Aeolian Islands off the north coast of Sicily, to not being able to see your own feet. But all in all the experience of Etna was unforgettable and though there were times when it was cold, windy and damp, and when everything tasted of acid (always bound to put you in a bad mood), I look back and think, this is a pretty cool thing to be doing for my PhD. Rob Martin is a PhD student in the Department of Earth Sciences

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Cambridge students build on nature s designs In the summer of 2005 we worked within a team of Cambridge undergraduates to produce the UK’s first entry for the annual International Genetically Engineered Machine (iGEM) competition. The competition involved 13 universities from around the globe. The challenge was to engineer living bacteria that could perform a specific task. Each team was given a ‘toolkit’ of standard, interchangeable parts called ‘BioBricks’. Each BioBrick is a DNA sequence with a known function; the DNA may code for genes or regulatory components (for example gene promoters). The teams were to design a simple biological system using BioBrick components and then implement their design in the laboratory using genetic engineering techniques. Tried and tested BioBricks are maintained in an online Registry of Standard Biological Parts (http://parts.mit.edu), a kind of virtual Lego box. To construct a bacterial temperature sensor, you can simply order the appropriate components from the Registry and put them together in a bacterial cell. Each BioBrick DNA sequence is flanked by four sites at which specific restriction enzymes can cut. This means that by following a series of simple laboratory protocols, BioBricks can be assembled together on a plasmid (a circular piece of DNA that can replicate independently of the bacterial chromosome) and this can then be transformed into a bacterial cell to test the BioBricks for functionality.

Our team decided to explore the feasibility of controlling the movement of bacterial cells (we used Escherichia coli as our model system). We began by looking at the sugar maltose, which is both an energy source and a chemoattractant (certain bacterial strains are attracted to maltose, and will actively move towards areas where it is in high concentration). Thus, we hoped that by controlling the cell’s response to maltose, we could control the movement of E. coli towards maltose. To exert a degree of control over the movement of E. coli cells via a natural pathway, we needed to be able to establish on and off switches for chemotaxis (the directed motion of an organism toward favourable environmental conditions, and away from those deemed unfavourable). We achieved this by adapting a ‘genetic switch’ to control the expression of the bacterial gene malE, which encodes the sequence information for Maltose Binding Protein (MBP). MBP is required for the detection of maltose and is essential for directed movement towards the sugar. To switch on MBP production we used a genetic switch, which utilised DNA recombination, that enabled the malE gene to be expressed in response to a specific chemical stimulus—isopropylbeta-D-thiogalactopyranoside (IPTG). Designing the ‘off ’ switch for chemotaxis proved to be more difficult, as MBP takes a long time to degrade once it has been produced. This means that after removal of the chemical stimulus (IPTG), MBP is still present and able to detect maltose. Following further investigation,

I n i t i at i ve s

Building with Biology we discovered a malE mutant that produced an unstable form of MBP that disappears within 45 minutes (a relatively short time period in terms of protein lifespan). Incorporating the malE mutant will be the next stage of the project. Our complete genetic circuit is shown in the box below (where some of the detail behind the circuit is also explained). The ‘wet lab’ phase of the project was a great experience for us all, especially the engineers who had never even used a pipette before. Unfortunately the end of the summer came all too soon, and we had to travel to Cambridge, Massachusetts to present our work at the Massachusetts Institute of Technology.All the competing teams congregated to present their projects in front of some of the biggest names in the field. It was truly amazing to see what each team, mostly or solely comprised of undergraduates, could develop in such a short time, with the quality of the work often rivalling that seen in published journals. After the presentations came the awards ceremony. The Cambridge team walked away with some of the most valued awards, including ‘Most Effective Approach’,‘Best Data and Data Visuals’ and, last but not least, the ‘Best Uniform’ award! www.plantsci.cam.ac.uk/Haseloff/iGEM2005 James Godman is a third year Natural Scientist specializing in Plant Sciences; Alice Young is a third year Natural Scientist specializing in Zoology; James Brown is a fourth year Engineer

A ‘traffic light’ system was used to allow the bacterial response to maltose to be visualized.This utilised the regulated production 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. 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 ‘flipping’ of the switch into the opposite orientation. This results in expression of malE instead of mCherry, and also in production of Green Fluorescent Protein (GFP): the cells are now green, and are producing MBP.Thus the cells which can produce MBP (and, therefore, detect the presence of maltose) are green.

initiatives@bluesci.org

James Brown

Bacterial Traffic Lights

The production of c1434, which represses Hin production, acts as a negative feedback loop; it prevents the production of too much Hin and thus prevents continuous ‘flipping’ of the Flipase Switch. If maltose is present, MBP binds to it, and this complex is able to activate production of the orange fluorescent protein mOrange, making cells that have detected maltose (and will move towards it) appear orange.

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History

An Original Thinker

Eastbourne, 20 June 1861: Frederick Gowland Hopkins is born. The future will see him make a resounding contribution to science for which he will later be awarded the Nobel Prize for Physiology or Medicine. It will also watch as he establishes the Department of Biochemistry in Cambridge and sets the remit of modern biochemical research, here and worldwide. Hopkins showed a scientific curiosity from an early age. When he was a young boy, his mother presented him with a microscope which he used to study the many forms of life on the Eastbourne seashore. At City of London School, he excelled in several subjects but it was his performance in the sciences which brought him particular recognition: he was top of his class in chemistry and by the age of 17, he had already published a paper in The Entomologist, a journal on the science of insects.

“

Hopkins defined biochemistry as a science combining chemical rigour with biological instinct

”

After leaving school, Hopkins trained in analytical chemistry, graduating from University College London in the shortest possible time. He next embarked upon a medical degree at Guy’s Hospital, London, remaining there after qualifying to work as a demonstrator in toxicology and physiology. Whilst in London, he began using his chemical training to investigate biological substances associated 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 proteins, thanks to his years at University College London. In the Cambridge Physiology Laboratory, he turned this

expertise to purifying the known food groups: proteins, carbohydrates, fats and minerals. Hopkins was thus able to conduct 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 lacking were then known as accessory food groups but are now called vitamins. They did not belong to any of the known food groups but were believed to be just as important for growth. However, Eijkman’s findings alone did not herald the beginning of medical research into dietary deficiency diseases, as understanding of this new field was rudimentary and it was difficult to demonstrate conclusively the essential nature of vitamins for growth. With his systematic feeding experiments on mice, Hopkins was able to show definitively that vitamins were required for normal growth just like the basic food groups. Thus, Hopkins demonstrated the physiological necessity of vitamins, thereby closing the gap in this body of work. The work of Hopkins and Eijkman gave rise to a new area of research, aimed at elucidating the role of vitamins in growth and dietary deficiency diseases. This contribution to medicine and society was recognised in 1929, when the pair were awarded the Nobel Prize for Physiology or Medicine for the discovery of vitamins. This Nobel Prize winning work was conducted in the Physiology Laboratory, Cambridge, a place where physical approaches, rather than chemical, were used to study physiological problems. Here, Hopkins’s chemical research was seen as an unnecessary drain of limited resources. Pressure grew to establish a separate biochemical chair for Hopkins. It took some persuasion on the part of Hopkins and his colleagues but eventually, in 1914, the Cambridge Department of Biochemistry was established with Hopkins as its first Professor.

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All images courtesy of the Department of Biochemistry

Varsha Jagadesham explores the legacy of Frederick Hopkins

First issue of Brighter Biochemistry

Hopkins’s 1912 paper on the physiological necessity of vitamins was considered a seminal work in nutrition and biochemical research. But it set another, more subtle precedent: a move from crude output/input studies to investigations at the level of biological processes and individual chemically defined molecules. In short, what we now know as modern biochemical research. Hopkins was an early champion of the importance of such research, and in 1913, he addressed the British Association for the Advancement of Science with his famous lecture, The Dynamic Side of Biochemistry. In this lecture, Hopkins defined biochemistry as a science “combining chemical rigour with biological instinct”. He expounded the simplicity of the chemical events that underlie biological processes, explaining the interdependence of these processes within the cell and their “underlying unity” in all organisms. He stressed the importance of fundamental research into all living organisms, in a challenge to the contemporary view that biochemical research was used by medi-

Lent 2006

History

cine for medicine. Hopkins thus defined the boundaries of contemporary biochemical 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 biochemical 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 constantly pervades our laboratory”, and the following pages reveal a trove of satire, poems and ditties, as well as papers, such as ‘The Direct Determination of the Mentality of the Normal Adult’. It is apparent that members of the Department believed wholeheartedly in Hopkins’s vision. However, Hopkins’s leadership and the nature of the departmental research did not go unquestioned. There were mutterings regarding the significance and coherence of so many lines of research, and about the amount of time Hopkins was required to spend on administrative duties on account of this. There was also the persistent challenge that although fundamental biochemical research was important, medical objectives should still exist. Murmurs of discontent led to actions to re-orient

research and remove the administrative pressures from Hopkins. But these were futile, blocked by Hopkins’s resistance and the strength of support from members of his Department. Hopkins’s beliefs were propagated through members of the Department and through propaganda he published himself. However, what was called the golden age of the Department came to an end with Hopkins’s death in 1947, and the movement of members out of the school. It was some time after the Second World War when Hopkins’s vision of biochemistry began to resonate in laboratories once again, as money started to pour into the life sciences, enabling diverse fundamental research into all organisms which continues to this day. With his role in the discovery of vitamins, Fred Hopkins contributed to both science and society. But with his vision

for what biochemical research could and should include, and his belief in biochemistry as an autonomous science, he contributed to science and society once again—through his own work and that of the many who took his thoughts with them. Truly, Hopkins was “the father of British biochemistry”. Varsha Jagadesham is a fourth year Natural Scientist specializing in Biochemistry http://nobelprize.org

Further Reading Cambridge Scientific Minds edited by Peter Harman and Simon Mitton Hopkins and Biochemistry by Harmke Kamminga

Europe s scientists pull out all the stops as its historic organs fall silent. Mark Turner investigates The churches of continental Europe harbour some of the world’s finest and most ancient pipe-organs. These instruments, originally built in the fifteenth, sixteenth and early seventeenth centuries by such renowned organ builders as Friederich Stellwagen and Arp Schnitger were, in their time, some of the most sophisticated machines ever built and stand as shining examples of both technological and artistic achievement. Instruments such as the 1467 Stellwagen organ in the parish church of St Jakobi’s in Lübeck, Germany are prized for their unique tone qualities: aficionados rate this organ as one of the finest in the world for the performance of Renaissance and early baroque repertoire. The news therefore that the largest pipes in this important instrument were quite literally losing their voice, sent shockwaves through the organ playing and building community. Inspection of the instrument revealed the cause: small holes in the walls of the pipes. The organ had an acute case of lead corrosion. As word of the Lübeck Stellwagen organ’s symptoms spread throughout Europe, it became apparent that this was not an isolated case: similar rapid corrosion was afflicting historic organs across the continent. The pipework of these organs is crafted from lead, which is well known to corrode gradually under atmospheric conditions. However, the corrosion pattern in Lübeck was entirely new, characterised by the formation of a white chalky residue in the pipe interior which eventually eats through the pipe entirely. In 2003, research engineer Carl Johan Bergsten from the Organ Art Centre at Sweden’s Gothenburg University (GOArt) assembled a team of chemists, metallurgists, organ builders and historians, founding the Corrosion of Lead and Lead-Tin Alloys of Organ Pipes in Europe project, or COLLAPSE, to investigate. Chemical analysis of corroded and uncorroded pipework samples quickly began to yield clues suggesting that, of all things, well-meaning restoration may lie at the heart of the problem. The corroded lead contained higher than normal levels of organic acids— known to cause the rapid oxidation of lead to lead hydroxycarbonate and lead hydroxyacetate, responsible for the observed white residue. Further investigation and air sampling indicated the presence of acetic acid in the airflows of the stricken instruments. Why had this rapid corrosion suddenly appeared in instruments, some of which had otherwise survived for five hundred years? A possible source of acetic acid in pipe-organs is the oak wood used to line

Mark Turner

Arts & Reviews

Problems in the Pipeline

the bellows and the windchests on which the pipes themselves sit. In each of the corroding instruments, restoration work involving replacement of oak wood had taken place in the recent past. As wood ages, the cellulose forming its cell walls tends to break down releasing, amongst other chemicals, both formic and acetic acid.When fresh wood is used to line wind chests and bellows, this organic acid is released directly into the organ’s wind supply, from where it is carried into the pipes. Archaeologists and conservationists have long known the effect of oak on lead artefacts, and will always avoid storing such items in oak drawers or cabinets—but the organ building community has been slow to make this link. In the five hundred year lifetime of a historic organ such as that in Lübeck, the interior wood of the organ will have been changed several times. So the question rises once again, why is this corrosion only now apparent? Svensson’s work suggests that church central heating may be to blame: a recent addition to many European churches, this mod-

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ern concession to parishioner comfort may be driving off acid in the new wood faster than ever before. Catherine Oertel at Cornell University, collaborating with GOArt, employed a range of spectroscopic techniques to probe organ pipe composition, focussing especially on X-ray fluorescence spectroscopy. Here, an electron microprobe bombards the sample in question with a harmless stream of electrons, causing X-ray emission, with each element in the pipe’s composition giving a characteristic wavelength fingerprint. Pipe alloy composition also seems to be an important factor in determining susceptibility to corrosion. Almost all affected instruments in continental Europe were built in the Northern German tradition, using lead alloys with a low tin content of 1.5–2%. Lead is alloyed with tin, both to harden the organ pipes and to add lustre. Tin was extremely scarce and expensive at the time, and so European builders were directed by frugality. It is indeed the low tin content in the pipes of prized historic organs that contributes to their unique tone colour. This explanation is corroborated by the fact that British historic organs have so far not been affected by rapid pipe corrosion. At the time, Cornwall was Europe’s major source of tin: British organ builders therefore had ready access to a cheaper source of the metal, and their pipework often contains up to 20% in the alloy. Interestingly, addition of tin to the pipework alloy is not thought to directly provide resistance to corrosion. Optical and electron microscope analyses by researchers at the University of Bologna have shown that pipework with a low tin content tends to have higher levels of trace impurities such as bismuth and antimony—additives which can subtly alter the microstructure of the alloy. It could well be that understanding the effect of these trace impurities holds the key to unravelling the mystery of organ corrosion. Meanwhile, can anything be done to safeguard these instruments? Catherine Oertel favours either the development of a coating to be applied to wood components inside the organ, preventing the escape of organic acids, or the use of passive filtration systems to remove them from the wind supply. Bergsten at GOArt hopes to produce a protective coating for the pipes to protect from corrosion. For now, however, the pipework remains irreplaceable; and as more and more organs gradually lose their voice, organ enthusiasts can only hope that progress is swift. Mark Turner is a PhD student in the Department of Chemistry

Lent 2006

Please email your queries to drhypothesis@bluesci.org for your chance to win a £10 book voucher

Dear Dr Hypothesis, I exist mainly on a diet of toast, but, as my room is rather squalid and crowded, I often lose bits of toast down the side of the bed or beneath a book. Long contemplation of old toast has made me wonder: why is toast crisp and crunchy when it comes out of the toaster, but soggy shortly afterwards? Squalid Sarah

and colourless, so this should not cause you any undue embarrassment. Spraying deodorant simply under your arms should be enough to create a fragrant and favourable impression on your interviewers. Good luck! http://science.howstuffworks.com/sweat.htm

Dear Dr Hypothesis, I am a biology student graduating in the summer. I am worried about sweat patches when going for job interviews in the next couple of months. As I’m sure you’re aware, we are all sweating all the time over nearly our entire bodies, but we only put anti-perspirant under our arms. To prevent myself feeling uncomfortable, surely I should apply deodorant to my entire body? Is it worth my time doing this, or are there any shortcuts I can take? Nervous Nancy DR HYPOTHESIS SAYS: There’s no need to worry about this, Nancy, as there is sound scientific reasoning behind what I’m about to explain. You’re correct in saying that our bodies perspire over most of the surface, but the composition of sweat can vary. Only underarm sweat contains proteins and fatty acids (which leads to the stains you’re afraid of) and only this type of sweat is capable of supporting bacteria that produce the bad smell. Fortunately most other types of sweat are odourless

“When I hold a copy of BlueSci up to a mirror the writing appears back-to-front. Given that the mirror doesn’t seem to have a preferred direction, why doesn’t the writing also appear upside down?” One of our readers answered: The key to this question is to appreciate that the mirror does not actually laterally invert anything. Rather, it produces, at each point in the mirror, an image of whatever is directly in front of this point. In order to hold a copy of BlueSci up to a mirror it is necessary to rotate the magazine by 180¡ about a vertical axis. It is this rotation that performs the lateral inversion.To see how this is the case, imagine repeating the experiment with a copy of the magazine printed on a clear plastic sheet. Upon holding up the sheet in front of the mirror, with the text facing you, the text in the mirror is also the correct way round. Then, rotate the sheet to face the mirr o r n ow both the text on the sheet itself, and the image of the text in the mirror, appear laterally inverted.

DR HYPOTHESIS SAYS: This is a tough question as I am not aware of any scientific studies describing the properties of toast! However, I believe that the cause of this phenomenon is the moisture present within the bread.When you toast the bread it will heat up, turning this water into steam.The toast cools once it comes out of the toaster, condensing the water back into liquid form and making your previously firm toast appear damp.This explains the benefit of a toast rack: by holding the toast vertically, the rack promotes the loss of steam—there is then less water to condense and so your toast will remain firmer. Maybe a rack would be a good investment for you, Sarah? www.halfbakery.com/lr/idea/Heated_20Toast _20Rack

Dr Hypothesis asked:

Dear Dr Hypothesis, I had just finished tucking into a greasy meal of fish and chips when I noticed that I could practically see my copy of BlueSci through the once opaque paper where the oil had soaked through it. Why does this happen and why does it not work with things other than paper? Greasy Garrett DR HYPOTHESIS SAYS: The fibres in a piece of paper, such as a page of BlueSci, form a lattice, that is not quite perfectly arranged at the molecular level.This means that the light which hits the page is scattered and the unabsorbed rays are reflected, but at a wide range of angles relative to the angle at which they hit the page. Therefore, the light and the page will appear white. If grease gets into the fibres, it produces a more uniform lattice, so that the scattering of the light becomes more even.This actually reconstructs the light wave on the other side of the page, so it is now transparent! This phenomenon is only possible with paper, as opposed to materials like metal, because only paper is made up of fibres that can interact with grease in this way.

A Weighty Decision Dr Hypothesis research assistant Tom Pugh challenges you to try your hand at this mathematical mystery: You find yourself in a room with 20 bags of gold coins.You can take one bag away with you. However, 19 of the bags contain goldplated coins, each of which weighs one ounce. Only one bag contains solid gold coins, each weighing two ounces. A weighing scale is provided, but you are only allowed a single weighing to identify the bag containing the solid gold coins. How can you be sure to come away with the money? Visit www.bluesci.org for the answer.

Illustrations by Lizzie Phillips

Dr Hypothesis

www.av8n.com/physics/white.htm

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.

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Lent 2006

Corporate Services Graduate Programme

FINDING A CURE FOR CANCER DOESN’T STOP OUTSIDE THE LAB DOOR.

We’re one of the most high profile names in the not-for-profit sector. We have the sort of open, innovative culture and commercial awareness that’s associated with a progressive private sector business, but with a charitable aim. The difference is in the bottom line. Everything we do at Cancer Research UK has the same aim: to lead the fight against cancer. So when you join our new two year Corporate Services graduate programme you can be sure of twin benefits. Not only will you be beginning a high-level corporate career at the forefront of either Finance, IT, HR, Audit or Risk, but you will also be making a difference to thousands of cancer-sufferers and their families. Take the first step and visit http://www.cancerresearchuk.org/aboutus/ graduateopportunities/ For more general enquiries please email: corpgradscheme@cancer.org.uk Closing date for applications is 17th February 2006.

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