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16-19 yrs. RUNNERS-UP: ANNES WILTON, CLAIRE BANWELL, MARION SIMPSON,
MONICA DESAI, NICOLA CORNISH, NIGEL JACKSON,
RICHARD HALL, SAMUEL BUNTING, VICTORIA HOYLE

ANNES WILTON


Unearthed Discovery

Not all scientific discoveries are sensationalised miracle breakthroughs which could revolutionise life as we know it. Hidden away in laboratories across the world are the unknown scientists wrapped up in their own little world of investigation, their hard work and discoveries going relatively unnoticed. This is the story of such a discovery, the story of munsterol. In the space of a year this marine compound, previously unknown, has been unearthed, studied, documented and named.

In the summer of 1995 postgraduate student, Clare Norris was carrying out an MSc project under the supervision of Dr. Steve Mudge. He enthusiastically explained the whole process to me on a bright, sunny afternoon overlooking the Menai Strait from his office at the School of Ocean Sciences, University of Wales, Bangor. The aim of the project was to find out if fatty alcohols could be used to indicate terrestrial organic matter. This led to the discovery of an unknown substance in the project samples.

Dr. Mudge named the compound munsterol after that bizarre TV family, The Munsters' which reminded him of the distinctive odour of munster cheese that wafted from the project samples containing the compound. Collecting the samples from the Conwy Estuary, North Wales, was a bit of an epic. A boat was reversed down a slipway by a hire van. Then disaster struck! The van was not powerful enough to get back up. It was stuck on the gravel slip at low tide with the tide just about to turn! 'Thank goodness for mobile phones!' Dr. Mudge laughed. A local garage was contacted and a hasty tow was provided. "Collecting the samples, in the small boat, zipping up and down the estuary collecting mud - that was fun!'

Back in the lab there was laborious work to be done. "Doing extractions can be quite tedious, because it's repetitive, but as soon as you get some results you are driven to find out more and understand the system.' Analysis of the collected samples showed ergosterol to be present and a mass spectrum showed an unexpected peak. It was thought to indicate lichensterol, but analysis of lichen samples showed this not be the case. After further study of the mass spectrum Dr.Mudge put forward a structure of a new compound with a theory of its formation.

The compound in scientific terms is called ergosta 5, 8 (14), 22 tri-en 3-ßol, a monster of a name. It is believed to be a derivative of ergosta 5, 7, 22 tri-en ßol, (ergosterol). Ergosterol is common to fungi, a so called bio-marker. Fungi invade vegetation such as leaves and twigs in the woods and this material is washed into the estuary. In the marine environment, ergosterol undergoes diagenesis a degradation process. The 5,7 di-ene structure is unstable in certain sediment conditions so the double bond moves to a new position to make this new compound, munsterol. The structure was confirmed by Torren Peakman and Jack Eglington at the University of Bristol and the compound now appears on the Chemical Abstracts Registry.

But it does not stop there. "It's not, "OK, we've found a new compound, let's go and look for another one." There are many aspects to be researched further.' A proposal has been put forward to NERC (Natural Environmental Research Council) to do this. This compound could be useful to people using biomarkers in environmental work. If ergosterol is in mildly reducing, anoxic sediment then formation of this compound occurs. We can use the ratio between the 'parent' compound ergosterol and munsterol to see how far along the process it has gone. For example in the field of palcooceanography you could take a core of sediment going back say 12,000 years to find out at what time certain conditions of sediment existed.

Is there is a geographical relationship of the formation of this compound? Comparative sediments from the other side of the globe in Canada, and down in sunny Portugal showed lower concentrations of munsterol than in the Conwy Estuary where the maximum concentration was 0.7 µg/g (micrograms per gram). Is the transformation dependant on conditions such as climate? All these and more questions can be looked into.

OK, so it is not going to have earth shattering effects, but for the few it is a fascinating and useful find. And we all know that old Star Trek saying: 'The good of the one...'

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CLAIRE BANWELL


TB Vaccines Show Protection Against Leprosy... But Not TB!.

There are no vaccines for leprosy so it was very exciting when the results of Africa's largest vaccine trial indicated that tuberculosis vaccines greatly increased the body's resistance to leprosy - one of the world's most disabling diseases. But at the same time there was disappointment because the same vaccines provided little protection against TB, which is the largest killer amongst all infectious diseases and one that causes intense pain and relentless wasting away to over 3 million people every year.

Using funding primarily from The British Leprosy Relief Association (LEPRA) a long term research project into leprosy began in l98O. Over four years the entire population of the Karonga District, Malawi, was surveyed approximately 112,000 people were examined for leprosy, charactenstics which would help in identification such as scars and birthmarks were noted. The pattern emerged that those with scars from the Bacille Calmette-Guerin (BCG) vaccine were much less likely to have leprosy, but even at this stage, the research showed no evidence of protection against TB.

The BCG vaccine is used to protect against TB and has been widely used in the United Kingdom for over 40 years. It is prepared from an artificially weakened strain of cattle TB, which provokes a natural resistance to the TB bacteria found in humans called Mycobacterium tuberculosis. This rod-shaped bacteria is similar in construction to A. Leprae which causes leprosy, but they attack the body in different ways: leprosy damages the nerves and can cause deformities such as twisted limbs, whereas TB mainly infiltrates the lungs and can be fatal.

Some countries, such as Brazil, already give repeat BCG vaccines to children because of its links with leprosy, but there have been no new programmes due to these findings. As Doug Soutar, the Programmes Manager of LEPRA explained, "the outcome of the project has been to raise more questions rather than provide practical implications."

Two of the biggest questions yet to be answered are why the repeat BCG vaccines didn't provide resistance to TB and why they protected against leprosy. Mr. Soutar added, "there have always been discrepancies in the effectiveness of the BCG vaccine. The United States of America for example don't use the BCG vaccine because initial studies in the 1950s showed that it was only 30% effective against TB, whereas it was shown to provide 80% protection in the United Kingdom." These differences suggest that other factors affect the way the BCG vaccine works. "As the Malawi project was long term, a number of other factors varied and it is these factors that need to be evaluated. For example, living conditions improved over this time and the treatment of leprosy using multidrug therapy has rapidly increased since it was first used in 1982. Another theory is that other environmental microbacteria (e.g. those present in water or soil) interact with the immune system changing the way it behaves."

It is the immune system that is expected to become the focus for research over the next five years. There are hopes that better vaccines can be designed and that the effect of the human immunodeliciency virus (HIV) can be further assessed. There are terrifying prospects that HIV (which attacks the immune system leaving the body susceptible to diseases such as TB and leprosy) could increase the number of deaths from TB by millions. But the Malawi project must remain a success story because it is the only combined leprosy/TB vaccine trial in the world. One day the results may lead to the discovery of a leprosy vaccine.

If detected early enough, both diseases can be cured with multidrug therapy, a combination of strong antibiotic drugs that act either by killing the bacteria or by preventing them from multiplying. Yet poor living conditions, inadequate health care systems and no Funds to buy drugs or vaccines have meant that both TB and leprosy continue to flourish in developing countries.

In 1986, to understand further the link between the BCG vaccine and leprosy, Professor Paul Fine and Dr. J.Nl. Ponnighaus from the London School of Hygiene and Tropical Medicine set up an extensive vaccine trial. Researchers returned to the Karonga District where 121,000 people agreed to take part in the trial. Each person was given either a single BCG vaccine, a repeat BCG vaccine or a trial experimental vaccine combining BCG plus killed leprosy bacilli.

The results of the trial were published last year and they showed that a second dose of BCG vaccine could prevent 75% of leprosy cases. On the other hand, the additional BCG failed to provide any protection against TB and there was no evidence that the addition of killed leprosy bacilli contributed to protection against either disease.

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MARION SIMPSON


Dolly's No Mixture

"Pass the salt, Albert!" There was a lull in the animated conversation round the dinner table. Pythagoras continued to doodle triangles on his napkin. Newton threw his breadroll up in the air, while the others giggled at Darwin's monkey impression

Imagine a table around which sit the great thinkers of the past, recreated by the miracle of genetic engineering. Less incredibly, imagine that a modern-day scientific genius was never allowed to die, being regenerated in several editions from genetic material. A recent arrival in a laboratory in the east of Scotland has opened these avenues of possibility, inciting talk of six-headed chickens and eight-footed lambs, and prompting a demand from President Clinton for in-depth investigation. Her name is Dolly and she is a sheep.

Dolly is the result of several years' research at the Roslin Institute in Edinburgh. She is the first sheep of her kind in the world because she is a clone; genetically identical to her "mother". She is not the first sheep ever to have been successfully cloned, since Dr Ian Wilmut and his team at the Roslin Institute achieved this in 1995, using tissue from an embryo to produce Megan and Morag, but Dolly is the first sheep ever to have been developed from an adult cell.

The process used to create Dolly does not involve male-female reproduction but a single cell from a piece of non-reproductive tissue taken from an adult ewe. This cell is combined with an immature, unfertilised egg, called an oocyte, taken from the ewe's ovaries. The oocyte is "wiped clean" of DNA by the removal of all its chromosomes so that when it is fused with the donor tissue, using an electric current, one cell called a blastocyst is produced. This is then implanted in a surrogate mother and carried to delivery.

In the past, cloning has only ever been achieved using donor tissue taken from an embryo, and efforts involving older tissue resulted in chromosomal abnormality, but in Dolly's case, cells from an adult udder have been used. This attempt has been successful because of a co-ordination between the cell development cycles of the donor tissue and the recipient egg. In order to do this, the research team used a donor cell in a state of quiescence, which means that it was not going through the cell growth cycle. They generated this quiescent state by starving the cell, placing it in a saline solution with the bare minimum of nutrients. Thus when the donor cell was fused with the egg, they grew as one.

Now that the cloning of an adult mammal has been shown to be possible, many people are asking how long it will be before we can all have a carbon-copy of ourselves, to use as an organ bank, a fourth at bridge or even a body substitute, for those rainy days when we can't be bothered getting out of bed to go to work. However, the technique used to clone Dolly is fraught with risks and unknowns (not to mention the worldwide ethical controversy it has caused).

From the cases of human cloning which already exist, namely identical twins, who are of course individual people, and are formed by their environment and life experience, we can see it would not be feasible to create a race of musical geniuses using cells from Beethoven's body, or to bring back Elvis in the laboratory. In addition, there are many unanswered questions about the technique which can only be explained by monitoring Dolly's development. It is not known whether this cloning technique could lead to infertility or premature ageing, and the trial-and-error experimentation required could have catastrophic consequences for its subjects. As yet, the technique is not perfect; Dolly was the only successful result of 277 fusions involving adult tissue, although the team also produced several other lambs, using tissue from an embryo and from a foetus. It also remains to be seen whether it is possible to clone using just any donor body tissue, or if certain parts of the body are unsuitable. It is thought that some cells, especially brain and nerve cells, may be too specialised in their operations to allow their cycles to be controlled, and it is not yet certain whether the technique may even be transferable to humans.

Human cloning is illegal in this country, and the research which led to Dolly was directed at agricultural applications. In many other countries, including the USA, no such prohibition on human cloning exists, and the possible consequences in terms of commercial applications and political misuse under tyrannical regimes are alarming. At the moment it is unclear whether Dolly marks the advent of an age of therapeutic genetic miracles or genetically enforced subordination. Layers of possibility remain to be explored.

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MONICA DESAI


E-vac-uating Cancer

Could Janet Thurman have avoided the months of pain and anguish that she suffered and would she have had to give up her unborn child if she had been treated earlier? Having been diagnosed as having cervical cancer in its late stages, she underwent a radical hysterectomy, even though she was three months pregnant, preventing her from having children again. For Janet Thurman it is too late now but for many women like her the future could be different. The race is on around the world to develop a vaccine against cervical cancer.

But why the anguish? Although in the western world, 80% of cervical cancers are found in screening and removed, world-wide, cervical cancer is the second largest killer of women after breast cancer with almost 500,000 new cases annually. In the UK alone, there are 144 new cases of cervical cancer per million people annually and Britain has the second highest recorded incidence in the EC. The statistics are frightening.

So what is the culprit? Certain types of Human Papillomavirus (HPV), which are sexually transmitted are believed to cause cervical cancer. The target of the virus is the transformation zone of the cervix which develops at puberty under the influence of oestrogen. This is the area which is sampled in smear testing. HPV infections are associated with the precancerous stage called CTN.

The most common variant is HPVl6. HPV can lie dormant in the cells of the cervix for many years but additional changes can occur, which enable the HPV genetic material to hijack the cellby docking into the host cell's DNA. The HPV genes E6 and E7 can then make products. These seize control of the products of the host cell that are responsible for regulating the growth and replication of the cells. This is a vital step that allows cells to become cancerous as this interaction causes the cells to replicate uncontrollably.

Since the cancer has foreign labels, or recognition proteins, it might be possible to produce a vaccine to marshal the patient's immune systems to kill the tumor cells. The body's army of killer immune cells tries to wage war against these cancerous cells and in some cases succeeds but the battle is full of problems. There are major complications. The labels, or recognition sites on these cancer cells contain an extra, simple viral protein, a peptide. Therefore, the killer cells' sensors have to be extremely specific. Even worse, the recognition sites are sometimes lost, so the cancer cells remain camouflaged. Producing a vaccine against HPV has proved even more difficult as it is not easy to grow HPV in a laboratory. Nevertheless, researchers all around the world are well on their way to producing a vaccine to prevent and cure cervical cancer.

A genetically engineered vaccina virus produces HPV E6 and E7 proteins stimulating the immunfty of patients with cervical cancer. This is a therapeutic vaccme. Clinical trials on this type of vaccine were carried out earlier last year by Cantab Pharmaceuticals in Cambridge and the University of Wales. Eight women who had advanced cervical cancer were given a vaccine called TA-HPV. Six died but three women showed an immune response. Two of these women survived fifteen and twenty-one months after treatment - a significant breakthrough.

The second type of vaccine is a disease preventing, or prophylactic vaccine. This has used insect cells and viruses to engineer proteins that make Papillomavirus-like particles which have external structures like that of HPV. This would induce antibodies to recognise and neutralize HPV whenever it enters the body. This vaccine could be given at birth as the immune system would keep memory cells in the system to attack at the first sight of HPV.

I asked Dr. P. L. Stern at the Paterson Institute for Cancer Research in Manchester how far trials for the disease preventing vaccine had progressed. He said, "Successful animal trials have taken place but it will still be several years before a vaccine will be available for use in humans. However a vaccine against an HPV which causes genital warts has shown very encouraging results in early trials in patients."

There are, however, still questions to be asked. The vaccine would benefit the third world the most, so who would fund the mass innoculation? Are there cheaper alternatives, like encouraging the use of condoms? Unfortunately there are several different types of HPV which can cause cervical cancer, so how many vaccines will we have to keep on developing?

Thus, a cervical cancer vaccine is an excfting and realistic prospect. Most women would cheer at the prospect of a small jab instead of weeks of mental anguish, waiting for their cervical smear test results. This, however, may be little consolation for Janet Thurman.

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NICOLA CORNISH


The Animal Within

Since the first transplant operations were carried out in the 1960's, organ grafting has developed from a final attempt at saving life to become a standard surgical procedure. It is now possible to transplant all vital organs apart from the brain and many previously fatal diseases are treated in this way. The biggest problem is that the number of people waiting for organ transplants exceeds the number of organs available for transplantation.

So, scientists are looking towards xenotransplantation as an alternative source. This is the transplanting of animal organs into humans and there now exists the scientific and medical knowledge to carry out such a procedure. Many such operations have already been performed, although with limited success.

The first xenografts used organs from primate donors as it was felt that, being man's closest relatives, they offered the most suitable compatibility. Their use was, however, soon discouraged due to the high risk of transmission of disease from donor to patient, and the scarcity of higher primates. The next animals to be considered were pigs and, in many ways, these animals are ideal as organ donors for humans. They grow to an appropriate size, with their major organs being similar in structure and function to those of humans, they are easy to breed and feed at low costs and they are reared and slaughtered for human consumption in large numbers. However, the problems associated with transplanting organs from unrelated species are even greater than those of primates. Not only is there a risk of transmitting foreign diseases between species, but the human body's immune system has its own anti-pig antibodies which would lead to rejection of the transplant within minutes. Until these problems can be overcome, it seems that success of whole organ pig xenografts is unlikely.

One of the latest areas of research has been in the use of animal pancreas islets (the cells that produce insulin) as a treatment for diabetes. Diabetic's pancreases cannot produce enough insulin, a hormone that allows tissues to take up sugar required for respiration, and sufferers must survive on daily injections of insulin. However, injections cannot mimic the precise response of normal islets to fluctuating levels of blood sugar and eventually injected insulin may damage patients' eyes, hearts, nerves and kidneys. For a decade, scientists have been trying to transplant healthy islets but it takes three human pancreases to provide enough for one transplant. The possibility of using pig islets has been widely studied but four pigs are needed for one transplant. To treat a small percentage of diabetics each year would need a million pigs and the practical problems and cost of rearing the animals would be astronomical.

A group of Canadian scientists, lead by Jim Wright, at the Izacc Walton Killam-Grace Health Centre in Halifax, Nova Scotia, are now looking into the use of the tilapia, a fresh water fish widely farmed in the tropics. Unlike pigs, fish can be raised cheaply, at high density in small spaces. Tilapia also have two pancreases, one for digestive enzymes and the other for insulin. This means that it is much easier to isolate the islets from other tissue, thus reducing the total cost of the entire process further.

To overcome the problem of rejection without drugs, a method of encapsulating the cells in gel has been developed. This gel, derived from seaweed, allows sugar and oxygen in and insulin out, but excludes the cells and large molecules of the immune system. As blood vessels cannot grow into the capsules, human cells would suffocate. Tilapia, however, live in ponds with low levels of oxygen and their cells only need one-fifth of the oxygen required by human cells, so their cells survive encapsulation.

The biggest problem with using fish islets is that fish insulin differs from that of humans by seventeen amino acids so it works poorly. Jim Wright and his team have cloned and modified the tilapia insulin gene to produce human insulin and are now injecting it into tilapia eggs. If they can breed a stable line of fish that produce only human insulin, it seems that a long term cure for childhood diabetes is possible.

Of course, even if we manage to overcome all the practical problems associated with animal transplants, there are many ethical arguments which could prevent their widespread use. These all need to be discussed thoroughly and fair conclusions drawn before the use of animal organs can become an accepted, surgical procedure.

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NIGEL JACKSON


The Good Old British Chip

Nearly fifty years ago Britain was at the forefront of computer technology. On 21st June 1948 Tom Kilburn and Freddie Williams of Manchester University saw their Mark 1 computer work for the first time. All computers before this were built to carry out specific tasks; the Mark 1 was the first flexible universal computer. lt was the beginnings of the modern day computer. In 1974 Freddie Williams recalled the event saying "it was a moment to remember... and nothing was ever the same."

Today you may well believe that nothing is the same. There seems to be no similar achievements proceeding from our universities. You would be mistaken. For in that same computer science department at Manchester there is a great lateral thinking scientist: Professor Steve Furber.

In 1983 he led the hardware design team that began working at Acorn Computing for a successor to the much loved BBC Micro - that ubiquitous school computer that can still be found buried at the back of many supply cupboards nationwide. Professor Furber told me of the group's audacious approach to the task; "We started reading the papers published by Berkeley and Stanford on their RISC design and began to think that maybe we should try to design our own processor."

RlSC (Reduced Instruction Set Computing) processors were at that time only avail£ble at high costs for specialist computers. All home computers were then using CISC (Complex Instruction Set Computing) technology. The idea behind RlSC technology is that a sequence of simple instructions can be used to make up a single complex instruction. This sequence of instructions can then be executed more quickly, since the processor will generally operate at a speed defined by its longest instruction. The project therefore required a new programming language, so these instructions could be written into programs. They created the ARM (Advanced RISC Machine). Not only was it fast, the ARM chip was cheap to make and power efficient.

Despite the evident qualities of Acorn's ARM based computer, a combination of bad sales and marketing alongside financial troubles made them fail to dominate in the business market. Due to the great innovation employed by Furber and his design team, the resulting computers were not compatible with market leaders, due to the different instructions the processor required.

Today the basic ARM architecture is still alive, having been licensed to Digital Equipment Corporation of America who have vastly improved its speed. Though the latest incarnations of the ARM are useful to the British Computer Industry they are more french fries than chips.

At the historical heart of British Computing at Manchester University, Professor Furber has once again started the computer science department beating with the expectancy of another great achievement. Furber is going back to what he calls "the older and more anarchic approach" of asynchronous technology.

In just about every processor there is a clock, it co-ordinates all the different components of the processor by making them perform their task at the end of a clock cycle, signalled by an electrical pulse. The processor, however, will function at the speed of its slowest component. Furber has developed the Amulet along with other staff and students. It is a chip with no clock to synchronize it, fully asynchronous and very different.

Furber was inspired when he read Sutherland's Turing Award Lecture on Micropipelines from 1987. "The Micropipelines paper is beautifully written... and that started me thinking," he said.

Don't believe the clock can simply be taken away and the processor will magically work faster. The passing of information, or data, between components has to be facilitated by micropipelines. These micropipelines are labyrinthine techniques, basically making sure data is only passed on when needed, still allowing every component to execute its task as quickly as it can.

The Amulet is most likely to be sold on the merits of its power consumption due to its relatively slow speed. Most power wasted in an average chi p is due to the clock. Even when idle, the clock must be ready if the processor is suddenly required to work. The Amulet is fairly power efficient while in full flow, but when idle requires considerably less power, since there is no clock to keep pulsing.

Professor Steve Furber feels optimistic about the progress of the third version of the Amulet. With his experience and a strong team to help him Manchester University may realise a similarly great computing success, soon after the 50th anniversary celebrations of the Mark 1. Perhaps Furber's achievements are nothing like the same as that of Kilburn and Williams but it will be a while before they stop making good chips in Manchester.

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RICHARD HALL


Starlings and Natural Alcohol

It is probably a safe assumption that the science of alcohol is not a hot topic of conversation in your local pub. Neither is it likely that the natural world would be mentioned in any conversation that involved one of the most popular of the class of drugs referred to as 'socially acceptable'. However, one group of scientists have made a discovery that might just make you think a little more about it.

First of all, though, let me give you a little bit of background on the subject. Alcohol is a depressant drug (one which has an anaesthetic effect on the nervous system), and being rapidly absorbed into the bloodstream its effects on the brain are not long in coming. If taken in excess it will eventually be absorbed by the cerebellum, the part of the brain which controls movement, balance and co-ordination, causing walking difficulties and a tendency to collide with objects that are usually easy to avoid. This alcohol must be removed from the body. The vast majority of it is carried to the liver where it is converted into harmless products which can be assimilated or ejected by the body (i.e. it is metabolised). This metabolism is accelerated by an enzyme - a biological catalyst which alters the rate of a reaction while remaining chemically unchanged itself (a definition that should be ingrained on the minds of all biology students). The particular enzyme involved in the breakdown of alcohol is known as alcohol-dehydrogenase.

As well as its ability to aid the relief of stress when taken in moderation, alcohol is also used in another social context. It is a popular activity amongst students (so I'm told) to see which of them is best able to 'hold their drink'. In this fashion alcohol is used as a tool to assess social status, and the incapacitated losers often become an object of amusement for their rather-less-than-sober companions.

However, what if the consequences of dulled senses and physical ineptitude were more than just a loss of face? What if you were suddenly attacked by a predator while still in a drunken state? Admittedly, it is not likely that you would encounter a hunting tiger on a Saturday night in the middle of town, but consider what would happen if you weren't safe from attack by a deadly enemy.

This is where the discovery comes in. A form of natural alcohol, produced by wild yeasts fermenting the sugars in fruit, is a popular beverage for quite a few forms of wildlife. On warm summer days you may have witnessed, like I have, wildlife ranging from bees and wasps to house sparrows staggering about on the ground and careering into bushes and trees when attempting to take off. Until now I had not known what caused it, but apparently it is possible to have animal alcoholics. However, some animals are better equipped to 'hold their drink' than others, in particular the starling.

Roland Prinzinger and Ghassem Hakimi of the University of Frankfurt performed tests on European starlings, giving them diets containing what they thought was more than enough to get them drunk. Blood tests a short time afterwards, however, showed that it had taken just thirty minutes for the starling to absorb and begin breaking down the alcohol, and even a heavy dose took just two hours to be completely metabolised. This astonishing rate of breakdown is simply due to the fact that the aforementioned enzyme, alcohol-dehydrogenase, is working within the starling at a rate of activity around fourteen times higher than it does in a human. Birds that are usually seed-eaters, like the house sparrow, carry far less of this vital enzyme, which is why they are more likely to be seen drunk and disorderly in your garden!

As a prospective zoologist, the thing that interests me most about this discovery is the survival value that this heightened enzyme activity holds for the starling. It pays dividends to be able to glean good nutrition from a high-energy food like fruit while avoiding the side effects which would make it easy meat for a predator. Consider how much simpler it would be for an alert sparrowhawk to catch an inebriated starling.

It is indeed a sobering thought that this little bird, relatively speaking, could out-drink a human around 1,000 times heavier than itself!

A final word to all my fellow students. Remember the moral of this little story: the next time you see a starling, don't challenge it to a drinking competition.

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SAMUEL BUNTING


Yeast That's No Small Beer

"Ale man, ale's the stuff to drink/For fellows whom it hurts to think." So claimed poet A.E. Housman. No doubt, however, Mr Housman would have found cause to fret if his ale was stale - and the problem of preserving the flavour of beer is one which has occupied the brewing industry ever since it has been distributed from industrial breweries instead of the maltster's house.

Beer contains more than just malt, hops, water and yeast. It contains a whole cocktail of volatile chemicals, all of which add to the flavour of the beer. If exposed to air or left for long periods of time, these compounds will react with oxygen and the beer will go 'off'. Since even the most lowly lager-lout is disgusted by this, brewing companies have set out to find methods of preventing beer's flavour from spoiling.

Conveniently, beer contains naturally certain substances which prevent oxidation of its volatile components. These are sulphites, which are often added to foods because their antioxidant effect helps preserve flavour. The problem is that some of the yeasts used for brewing do not produce enough sulphites during fermentation to have a prolonged antioxidant effect. Jørgen Hansen and Marten Kielland-Brandt, two researchers at the Carlsberg laboratory in Copenhagen have found a solution to this problem by genetically engineering the yeast, known as Saccharomyces Carlsbergensis, which Carlsberg uses to brew their popular lager.

Inside each microscopic yeast cell is a molecule of DNA, one section of which carries the code which the yeast uses to produce a certain protein molecule. This is the MET 10 gene. The protein molecule it produces is used to make a substance known as sulphite reductase. It is an enzyme and is so called because it speeds up the reduction of sulphites to simpler substances which do not have the same antioxidant effect and therefore are useless in preventing the beer from going stale.

Hansen and Kielland-Brandt replaced the MET 10 gene with one which did not allow the yeast to make the protein molecule needed for sulphite reductase. The result was that sulphite reductase could not be made and sulphite levels built up during fermentation to 13-14 times the concentration found in normal beer. When the researchers did experiments to find what effect this would have on the concentration of the volatile compounds in the beer, they discovered that their levels remained higher, longer in the new beer. They concluded therefore that their technique improved the flavour stability of beer.

The sternest test was yet to come: approval by the taste panel. Several expert sups later came the cautious thumbs up - yes, the beer was satisfactory, but a difference in taste was noticeable. Carlsberg has no plans to use the new yeast.

Science has always had a major role to play in the brewing industry - brewing is often cited as the oldest example of biotechnology - with a 5,000 year history. Louis Pasteur first discovered the harmful effects of germs while helping out his local brewer, whose beer wouldn't brew. He discovered it could be treated by heating it strongly to kill the bacteria and developed 'pasteurisation', which is still used for milk and beer. More recently, Bass patented a plastic disc to which yeast sticks in cans of beer so that brewers can package 'live' beer in cans instead of the traditional bottles. Alpha Laval Brewery Systems have developed a system with which, by attaching yeast to small pellets of glass, they can ferment full-strength beer in two hours instead of the several days normally required.

The question is, at what poInt do we get so far towards the ultimate techno-pint as to lose the comfort of traditionaI real-ale? Some ale-drinkers may be concerned at the prospect of beer made with genetically engineered yeast, especially following the protests against the genetically engineered soya recently imported into Europe. It should be noted that Hansen and Kielland-Brandt bred their yeast so as to remove the antibiotic-resistance gene added in the gene replacement process which is proving so worrisome with the soya.

At least J.C. Jacobsen, founder of the Carlsberg laboratory would be happy. He thought: "It should be a constant purpose regardless of immediate profit, to develop the art of making beer to the greatest possible degree of perfection." One wonders what A.E. Housman would have thought of manipulating yeast's genes, but he can rest assured that with science's help, there will be ale for all for some time to come.

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VICTORIA HOYLE


Nature's Supercomputer

Picture the scene: dedicated computer scientists using the latest computer technology to crack foreign governments' high security encryption. Millions of computations are needed - but there are no sophisticated computer systems, no keyboards, no monitors - only rows of innocuous-looking test tubes. It is in these that the key will be cracked. Confused? Read on.

Electronic computers have evolved from the abacus through Babbage's Analytical Engine and 'adding machines' to the powerful systems used today in every aspect of our society. We have come to expect continuous improvements - more powerful, more compact, more user-friendly. But electronic computers use a labour intensive method of problem solving, checking every alternative in turn. Although each computation takes only a fraction of a microsecond, this means that for complex situations each additional variable adds significantly to the time taken. If the problem can be broken down into a huge number of very simple tasks however, then it may prove that a computer using the stuff of life itself DNA, will come into its own when silicon struggles to keep up.

So why are scientists manipulating solutions, test tubes and enzymes to come up with the same answer computer relics of 20 years ago did? A 'computer' using DNA can solve in days problems that take most people minutes, and a PC microseconds. They know that it is unlikely that DNA will ever beat or even rival silicon circuits at their own game. Lateral thinking is needed to find innovative ways of exploiting the inherent properties of DNA to achieve what electronic computers are sorely beginning to lack - the massively parallel processing needed for today's increasingly complex problems.

DNA consists of two strands made up of various combinations of 'bases', A, C, G and T. Bases A and T bind exclusively together, as do C and G. A strand with a particular sequence of bases can bind with another strand containing complementary bases in the same order, and not with other strands. It is this basic feature that provides the biological equivalent of binary code, the basis of computer programming. By creating strands corresponding to all possible solutions to a problem and applying a series of filters representing solution criteria, millions of strands can be thinned down to a single solution. The significant advantage is that billions of computations can be carried out simultaneously in one test tube.

Various ingenious methods are under development, some already having proved successful in limited applications. Leonard Adleman in 1994 was the first to solve a simple Hamiltonian path problem, a so called 'hard problem' using a five step algorithm, which in theory could be extended to solve considerably more complex situations. More recently the logic gates that conventional computers rely on to process binary code have been simulated using DNA. Molecular computing is taking its first tentative steps and its full potential is as yet unexplored. Admittedly, a test tube of DNA does not lend itself to the image of a personal laptop, but Adleman suspects 'molecular computers may fill a computational niche which electronic do not'.

Although electronic computers have developed out of all recognition from the monsters they once were, we cannot continue indefinitely building 'bigger and better'. At some stage even the most advanced computers will succumb to limiting factors of time, cost and hardware. As 'traditional' computers become more powerful they need more and more memory, whereas 'a single DNA memory could hold more words than all the computer memories ever made' according to Lila Kari. lt is estimated that to solve the US Data Encryption Standard program of DNA is needed. The main cost will be the enzymes needed for the biological filters; in theory 'biocomputers' would be thousands of times more energy efficient than silicon. Perhaps more significant is the exponential increase in time-consuming operations which means that some computations will simply never be completed using electronic computers, whereas DNA has parallel programming powers far exceeding the most up-to-date hardware available - as is evident all around us.

Is this the future direction for computing? Some scientists believe that DNA will never be useful enough to solve anything but the simplest problems. Clearly, however, DNA has already proved its superior computational powers The very fact that we are here is evidence enough - an incredibly complex living being resulting from many millions of basically simple operations systematically programmed, using the parallel processing that is biologically intrinsic to nature.

The study of molecular biology indicates that biochemical systems show parallels to the modern wonder and technological success of our time - the computer. But nature was programming its own 'systems' a long time before the first silicon chip was dreamt of. Our efforts are mere imitations. We didn't get there first. The cell did.

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