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NS 10 NOV 2001

Try again, Mr President
Bush's ill-conceived bioweapons proposals won't win any friends

US PROPOSALS to enforce the 1972 Biological Weapons Convention have come under heavy criticism since they were announced last week by President Bush.

Instead of coming up with new ideas, say experts, the US has simply revived some sections of a protocol that it rejected earlier this year, while ignoring crucial parts that it doesn't like. So despite the recent anthrax attacks on the US, few people expect any progress on enforcing the convention when its members meet in Geneva later this month.

The protocol rejected by the US had taken six years to negotiate. lt required governments to allow international inspectors to check any facilities suspected of being used to produce bioweapons, and to declare in advance any legitimate activity that might raise such suspicions. But the US

vetoed the protocol (New Scientist, 4 August, p 17), claiming that it would create a false sense of security while not actually catching cheats. lt promised to come up with alternative proposals this month.

But neither Bush's statement nor an internal White House briefing document obtained by New Scientist contain any original proposals. "Either they are goodwill measures, like ethical guidelines for scientists, which the US has rejected before as unverifiable, or they were already in the protocol," says Trevor Findlay of Vertic, a disarmament think tank in London.

It's what has been left out or watered down that will most annoy countries involved in past negoti6tions. Among the measures the US wants to weaken are those involving inspections and information exchange. Countries would not have to routinely declare biological research and manufacturing activities, information which is essential to guide inspectors, should suspicions arise. "That means an accusing country would have to put together all the information the inspectors would need, from scratch, unilaterally," says Findlay.

Bush's proposals also lack any provision for a specialised bioweapons agency to help with information and inspections. Instead, the onus would be on individual countries to gather enough evidence to convince the UN to send in investigators. Only rich countries would have the resources needed to do this. Having dismantled the package of hardfought compromises that would have given poor states an incentive to participate, Bush is now asking countries to put forward ideas-something that particularly enrages some observers. "We did, from before 1995 until 2001," complains Nicholas Sims of the London School of Economics. "You can't just [email protected] a carefully balanced agreement like @tocol."

European delegates to the Geneva talks are said to be planning to accept anything the US proposes that they think won't actually be harmful, just to keep the prospect of an agreement open. But developing countries, still smarting from this summer's rejection of their efforts, are unlikely to play along. Debora MacKenzie

Ready for anything
Warn the immune system an attack is coming and it can protect us from bioweapons

IT COULD soon be possible to temporarily boost people's immune systems to fight off all sorts of diseases, including anthrax. This could help protect travellers and people undergoing surgery as well as workers or soldiers at risk from bioweapons.

The method is based on a key difference between human and bacterial DNA. In people, when the bases cytosine and guanine occur together, the cytosine usually carries a methyl group. In bacteria, it doesn't. So when the vertebrate immune system encounters a "CpG" sequence containing unmethylated cytosine and guanine, it immediately mounts a generalised immune response that protects against bacteria and other pathogens.

Several teams are now developing synthetic CpGs that trigger this response. They have shown great promise in initial studies. Because a generalised response is quick and non-specific, it should protect people exposed to a wide range of bacteria, or to strains against which vaccines don't work.

Unpublished work by Dennis Klinman of the US Food and Drug Administration shows that immunisation with CpG sequences can protect mice from anthrax. Others have shown that CpGs completely protect mice from potential bioweapons such as Ebola, Listeria and tularemia.

The sequences also offer protection against parasitic diseases that could infect travellers and soldiers, such as those responsible for malaria, leishmaniasis and schistosomiasis. The studies have shown that CpGs induce an immune response that limits a pathogen's early growth and reproduction.

"I am convinced that these things are almost ready for prime time," says Robert Seder of the National Institutes of Health, who is working on CpGs in mice. Still, he cautions that: "we'll have to go with this carefully" in people. Tests on human cells suggests exposure to CpGs does produce good innate immune responses, but clinical trials have yet to be performed.

However, CpGs have already been tested on people for different reasons. Companies such as Coley Pharmaceuticals of Massachusetts have been trying to use CpGs as adjuvants-substances added to vaccines to boost the immune response. The trials so far show no serious adverse reactions from CpGs, says spokeswoman Patricia Dimond. Other teams are trying to use CpGs to prevent asthma (New Scientist, 2 October 1999, p 1 7).

Dimond would not say whether Coley Pharmaceuticals is interested in exploring CpGs as protective agents. But the company's chief scientific officer, Arthur Krieg, has said in the past that CpG DNA "may be a profoundly effective way to activate the body's natural immune defences to provide a broad-spectrum protection against biowarfare". Sylvia PagAn Westphat, Boston

Dirty dealing
Careless emissions trading may make pollution worse

POWER plant operators in the US are keen to trade emissions credits with each another as a way of staying within overall pollution limits. But unless the trades are carefully monitored, the strategy could make things worse.

Researchers in Texas, where emissions trading is already under way, have found that the location where pollutants are emitted can be just as important as the quantity. Get it wrong, and some kinds of pollution worsen.

Nitrogen oxides (NOx), for example, react with volatile organic compounds to produce sniog-forming ozone. If power plants near urban areas buy credits to belch out NOx, then smog can rise to levels that aggravate breathing problems. "There are scenarios where you can reduce NOx by half and wind up with a worse case of pollution than what you started with," says David Allen from the University of Texas in Austin. The Texan Emissions Banking and Trading Program has tried to tackle this problem by splitting the state into large areas, and only allowing companies to trade with others in the same area. But in the first detailed study of NOx trading, Allen and his team have found this isn't good enough.

The researchers created a computer simulation in which 50 power plants in eastern Texas were allowed to trade with each other. They found that I in 10 trading scenarios created a quarter more ozone pollution than if the same cuts were spread equally across all the power plants. And a few trades in the wrong direction resulted in worse pollution than if there had been no emissions reductions at all. On the other hand, some trades virtually doubled the reduction of ozone, they will report in an upcoming issue of Environmental Science and Technology.

Allen says that stopping the top 10 per cent of polluters from buying NOx credits would solve a lot of the problems. Matthew Baker from the Emissions Banking and Trading Program says they are taking the scientists' views on board, and accepts they may need to fine-tune their trading system.

Allen suspects the same thing might happen with other pollutants that cause local problems and have complex interactions with the environment-like mercury, for example. Nicoia Jones

Family brains
like it or not, you've inherited your parents' intelligence

YOU can claim to have inherited the family nose without inciting controversy. But the mere mention of inheriting the family brain makes people shift uncomfortably. Say that the grey matter passed down through the generations affects how smart or stupid you are, and you're as good as shunned.

Yet that is precisely what scientists in the US and Finland have found: genes strongly influence how certain parts of our brains develop. And the parts genes affect most are those that govern our cognitive ability. In short, you inherit your IQ.

That doesn't mean your intellect is set in stone, says Paul Thompson at the University of California at Los Angeles. But it does mean that your genes set the limits on your intellectual prowess. And, say neuroscientists, this may one day help us target the areas of the brain that respond most to environmental stimuli, where the potential for improvement may be greatest.

Thompson and his team studied 10 pairs of identical and 10 pairs of fraternal twins. Identical twins share the same genes, while fraternal twins share half on average. Because twins usually grow up in a similar environment, any differences between the two sets of twins can safely be put down to their genes.

The team used a medical MRI scanner to study the brains of the volunteers, selected ftom a Finnish twin registry. All twins were same-sex pairs born between 1940 and 195 7. Identical and fraternal pairs were matched for age, gender, handedness, social class and how long they'd lived in the same house.

The researchers found that certain regions of the brain were highly heritable. These included language areas, known as Broca's and Wernicke's areas, and the frontal region, which is one of the areas that plays a huge role in cognition. In identical twins, there was a 95 to 100 per cent correlation in these areas between one twin and the other-they were essentially the same. The frontal structure, says Thompson, appears to be as highly influenced by genes as fingerprints. "It's extraordinary how similar they are," he says.

The finding suggests that environmentthe twins' personal experiences, what they learned in life, who they knew-played a negligible role in shaping that part of the brain.

Fraternal twins had very similar Wernicke's area, showing about 60 to 70 per cent correlation. But they were less similar in other areas. You'd expect no correlation in random pairs of people.

Even more interestingly-not only was this grey matter highly heritable, but it affected overall intelligence, too. The volunteers each took a battery of tests that examined 17 separate abilities, including verbal and spatial working memory, attention tasks, verbal knowledge, and motor speed.

These tests home in on what's known as llg", the common element measured by IQ tests. People who do well on one of these tests tend to do well on them all, says Thompson. It's not known exactly what g is, but these new findings suggest that it is not just a statistical abstraction. Rather, they point to a biological substrate for g in the brain, says Robert Plomin, of the Institute of Psychiatry in London.

But Stephen Kosslyn of Harvard University questions whether g should be called intelligence. It picks up on abilities such as being able to figure out how to order things according to rules. "It's the kind of intelligence you need to do well in school," he says. "Not what you need to do well in life."

Kosslyn also says that many genes turn on or off in response to what happens in the environment. This means that learning and experience can indeed boost your intelligence within its predetermined range.

He thinks that the study may eventually help us target education to areas of the brain that are most responsive to environmental stimuli, such as the sensory areas. Alison Motiuk More at: Nature Neuroscience ontine (DOI: 101038/nn758)

Cotton-pickin' farce
Confusion threatens to send part of the Indian cotton crop up in smoke

FARMERS in Gujarat in western India who were preparing to harvest over 2000 hectares of cotton have been told to torch their crop because it is a genetically modified variety supplied to them illegally. The crop contains the Bt gene added to cotton by Monsanto, which makes the plant resistant to the bollworm that devastates almost half the annual cotton crop in India. Because the sale of transgenic crops has yet to be approved in India, the Genetic Engineering Approval Committee (GEAC) has ordered the Gujarat government to burn all standing crops, destroy all seed from them and test any lint that may already have entered the market. Yet clearance for the commercial produc tion of Bt cotton had been expected by the end of the year. Farmers' organisations are protesting, and it is not clear if Gujarat will risk their wrath by complying with the government's orders.

Who will pay compensation is also unclear. The GEAC is prosecuting Navbharat Seeds, which supplied the farmers. But the company says it developed the seeds through conventional hybridisation and was not aware that they contained the gene.

Besides Gujarat, Bt cotton was being grown clandestinely in Andhra Pradesh and Punjab states. But Prasanta Ghosh, a member of GEAC, dismisses fears of poor regulatory control. "The magnitude is insignificant, considering that cotton is grown over nine million hectares in India," he told New Scientist. "We have a stringent system.' But stopping unapproved GM crops being grown has proved difficult even in more industrialised countries. For example, last year hundreds of farmers in Britain, Fiance and Sweden had to destroy fields of oilseed rape. The Maharashtra Hybrid Seed Company (MAHYCO), in which Monsanto has a 26 per cent stake, has been conducting field trials of Bt cotton in India for the past five years. If Bt cotton is approved in India, Monsanto will not be able to impose the strict conditions farmers face elsewhere, such as having to buy new seed from the company every year. "The case is different in USA and Canada which have strong patent laws, agricultural laws and licensing-fee concepts," says a spokeswomen. Padma Tata

India allows sale of GM cotton Thursday, 6 December, 2001, 18:33 BBC

The date for the sale has not been set yet By the BBC's Alastair Lawson in Delhi

The Indian Government says it will soon allow genetically modified cotton crops to be sold commercially for the first time.

The head of the Department of Biotechnology, Manju Sharma, told the BBC that a date for the sale has not yet been set.

The announcement by the India is the culmination of over a year's experiments involving GM cotton crops.

Tests positive

The Biotechnology Department says the tests have been positive.

That means that GM cotton will soon be sold commercially throughout India.

The crop trials have taken place in 40 locations across the country's main cotton-growing areas, including the states of Maharashtra and Gujarat.

Resistant crops

Such crops are resistant to cotton bollworm, which causes heavy damage to India's cotton harvest.

This has experienced low yields for several years in comparison to developed countries.

India devotes more land to growing cotton than any other country in the world, but it produces far less per hectare.

The government research into GM crops has already been strongly criticised by the environmental lobby who are likely to be incensed by the latest news.

Moratorium

They have called for a 10-year moratorium on field trials and production.

Some cotton farmers argue that many who are opposed to GM seeds are acting in concert with the domestic seed and pesticide companies who want to protect their interests.

The government announcement is also likely to be criticised by those who argue that it contradicts its stance against multinational companies who it has criticised for acquiring patents on staple foods such as rice.

Quantum Knots
SOMETIMES it's hard enough just to find your shoes in the morning. Now you'll have to get used to the fact that tying the laces can entangle you in aspects of quantum theory. A Polish physicist has recently made the remarkable observation that, just like matter and energy, knots are quantised. The implications are still not well understood, but it has added a new twist to the branch of mathematics known as knot theory, and may @ave applications elsewhere. It could help unravel the mysteries of how DNA coils itself into tight tangles to fit inside a cell nucleus. And it might even shed lig ht on quantum physics.

This surprising discovery began when Piotr Pieranski of the Poznan University of Technology in Poland wrote a computer program that takes a given knot and, simulating a process in which the rope shrinks, produces what knot theorists call its "ideal" configuration. Until recently, mathematicians studying knots never worried about the properties of the rope or string used to tie their knots. They were only concerned with the way the knot wrapped around itself and ignored real-life questions such as whether a particular knot can be constructed in practice. Their mathematical knots were constructed out of string that had no thickness, just as the figures of geometry are constructed from idealised lines with no thickness. In the real world, of course, thickness makes a difference: for example, there are lots of knots you can tie with a thin length of string that you can't using the same length of thicker garden hose. The crucial factor for tying real knots is not the width of the string, but the ratio of the length to the diameter. The smaller this ratio becomes, the harder it gets to construct a given knot. Below a certain threshold in this ratio, you can't construct the knot at all. There are different ways to tie any particular knot, and for a given length of string some con figurations are easier to tie than others. Knot theorists-Pieranski among them-assume that each

knot made of real string can be manipulated into an ideal configuration that minimises the length of string used. It is just an assumption, however-no one has ever proved that each knot has a unique ideal configuration. Once it had produced an ideal configuration, Pieranski's program then went on to calculate what is called the writhe. This is a number that measures the overall degree of "inter-twistedness" of the knot. To calculate the writhe, you start with a 2D projection of the knot essentially the shadow it would cast if you were to shine a light on it from a particular angle. Then you examine the way the shadow crosses over itself as you follow it round. Imagine the rope is a oneway street. When you cross over another part of the street, does that other part run from left to right or from right to left? If it's going to the right, count it as +l. If it's going left, count it as -1. Once you've done this for all the crossing points, the total of these numbers gives you the 2D writhe of the knot from that particular angle.

But this view from one angle is not enough to tell you what a knot is really like. Even a very simple knot will look different from different angles. So knot theorists calculate the knot's writhe-also called the 3D writhe-by measuring the 2D writhe from all possible angles and then calculating the average of these values. Since there are infinitely many viewing angles, researchers use computer programs to calculate an acceptably accurate approximation. Pieranski's program calculated the 3D writhes of all ideal, alternating, prime knots with up to nine crossings. A knot is alternating if the crossings alternate between over and under as you go round the knot. It is prime if you can't split it into two simpler knots. The computer plotted the knots along the horizontal axis and their writhes as points up the vertical axis. At first glance, the plot of the results looked like a random scatter of dots. But then, being a physicist, Pieranski did something that few mathematicians would think to do. He picked up the printout and looked again from a shallow angle to see if he could detect any pattern in the spread of the dots. What he found amazed him. All the 3D writhe values fell along evenly spaced horizontal rows.

Pieranski thought it might have been a fluke so, with the help of his PhD student Sylwester Przybyl, he ran his program again on a much wider range of knots. For about 200 alternating prime knots with up to 10 crossings, the result was the same: each one's 3D writhe fitted into a particular row. It was like looking at the evenly spaced energy levels of electrons in an atom. Knots, it seems, have their own quantum theory.

The discovery amazed everyone in the field. Since it was made by simulating the ways ideal knots are actually tied, Andrzej Stasiak of the University of Lausanne won dered if the same result would come from using a purely theoretical approach. Together with mathematician Corinne Cerf of the Free University of Brussels, Stasiak showed that it could. Cerf and Stasiak proved that the 3D writhe of ideal knots has to be quantised, and that the quantum for knot writhe is 4/7. It fits perfectly with Pieranski and Przybyl's analysis: the 4/7 quantum provides the best fit for the 200 writhes they worked out.

So far, no one really understands why the 3D writhes of ideal knots seem to prefer par ticular quantised values, nor what is special about the number 4/7. Even so, Pieranski does seem to have stumbled upon a deep and fundamental property of knots that no one had even suspected might be there. His result is to be published in a forthcoming issue of The European Physical Journal E. Cerf and Stasiak have already published their theoretical work in the Proceedings of the NatiotialAcademyofSciences (vol 97, p 3795).

Knot researchers are now working to unravel the implications of the mysterious quarftum writhe. It could be hugely signifi cant, because knots form an integral part of the processes of life, and may even be at the heart of how our Universe works.

DNA, for example, routinely gets knotted. That's because a copy of an organism's DNA-which is millions of atoms long-has to fit inside the nucleus of each cell. To do that it "supercoils", winding itself up like a telephone cord, and during this process the strands get tangled and knotted. When the DNA is copied it has to be uncoiled, because reading off its genetic information requires untangled and unknotted DNA.

Enzymes called topoisomerases do this job. They free the strands by slicing through crossover points, pulling the two ends free from the knot and then reconnecting the straightened strands. Quantisation of knots makes this complex process much harder. DNA isn't like an ordinary rope, where you can join two ends at any orientation. Its structure, a double helix, means the ends cannot be connected unless they match up in exactly ihe right way. If the knots in DNA had integer writhe, cutting and rejoining them would be a simple matter, Pieranski says. Integer writhe would mean that the cut ends could be matched together without any re-orientation. But because the writhe numbers are clustered around multiples of 4/7, the enzymes usually have to cut a given DNA knot in several different places in order to undo the supercoiling. In short, the quantum nature of knots means that nature has to work much harder-and more slowly -to manipulate DNA. Writhe quantisation could also have important consequences for physics, though they may prove much harder to pin down. Some theorists trying to unify Einstein's theories of gravity with quantum mechanics postulate that everything in our Universe is made of tiny vibrating loops coiled up in higher dimensions-the "strings" of string theory. Crucially, these tiny filaments can be knotted, and that means knot theory may have something to say about why the Universe looks the way it does. Quantum theory itself might even be a product of the quantum nature of knots. At the moment, the idea is wild speculation. What's more certain is that when it comes to understanding knots, the road ahead almost certainly has more twists and turns. The quantum nature of knots was a surprising discovery whose implications are still largely unknown. "It glitters," Pieranski says. "But is it gold?"

Keith Deviin is a mathematician at Stanford University, California. His latest book is The Maths Gene, published by Phoenix, E7.99

NS 17 nov 2001

Global warning
Is the UN wrong about climate change leaving billions to starve?

AS CLIMATE talks in Marrakech drew to a close last week, the UN Environment Programme issued a stark warning of what global warming could do. Harvests of vital crops like rice, wheat and corn could plummet by a third over the next hundred years, it said, leaving billions to starve. The UN body rang the alarm bells as part of a last-ditch effort to persuade the US and others to ratify the Kyoto Protocol on limiting greenhouse gas emissions. But experts contacted by New Scientist say that whatever the other consequences of global warming, its effects on crops are much more complex than UNEP is claiming. And the US stuck to its position that the Kyoto deal is not the best way fix the planet's climate. Delegates from 1 78 countries attended the Marrakech talks to finalise the wording of the Kyoto Protocol. It was also seen as a golden opportunity to convince wavering nations to ratify the protocol and join a global coalition committed to fighting climate change.

UNEP quoted alarming studies by the International Rice Research Institute (IRRI) in Manila, Philippines, showing that crop yields can drop by 10 per cent for every 1 'C temperature rise. They also predicted a dramatic decrease in the land area suitable for growing cash crops of coffee and tea, including almost all of Uganda (see Graphic). Those are stunning effects. But according to Mark Rosegrant of the Washington-based International Food Policy Research Institute, which studies food production in the developing world, these figures are contentious. "The finding of a 10 per cent reduction in yield per 1 'C increase in temperature is not necessarily a consensus among climate scientists,' he says. 'Many believe that to 2020, and maybe even 2050, the net effect of global warming on crop yields will be positive." Increasing carbon levels in the atmosphere could help make crops more fertile, he says, more than counterbalancing the direct effects of global warming. A sophisticated study from the IRRI in 1995 concluded that while crop yields would fall by 4 per cent over the next century throughout Asia as a whole, they would probably go up in Indonesia, Malaysia, Taiwan and

Should we worry?
Report into birth defects near nuclear plant falls short of an all-clear

BIRTH defects around a factory in Britain that makes radioactive materials are 20 per cent higher than the average for the area, according to a government study. Radioactive emissions from the Cardiff plant run by Nycomed Amersham to make isotopes for the pharmaceuticals industry had previously been blamed by environmentalists for harming babies. It is Britain's second biggest radioactive polluter after the Sellafield nuclear complex in Cumbria. The local health authority Bro Taf commissioned the Small Area Health Statistics Unit at Imperial College, London, to investigate infant health within a 7.5-kilometre radius of the plant. Its study, published last week, showed that 907 babies were born with congenital deformities between 1983 and 1998, slightly more than you would expect in this part of Wales. Max Wallis of Friends of the Earth Cymru says this is "dynamite" because it vindicates environmentalists' claims. A report in 1999 by a local campaigner linked aerial emissions of radioactive tritium from the Nycomed plant with an increase in the number of infant deaths. But Bro Taf and Nycomed Amersham argue that the latest study provides no clear evidence of a link with pollution from the plant. The only statistically significant excess in birth defects was in families who lived between 2 and 7.5 kilometres away-and the excess is in comparison with birth defect figures for Wales that are incomplete, they say. "There is no credible evidence that the plant has caused harm," concludes Mark Temple, a public health consultant with Bro Taf. Nevertheless, he stresses that there is still a need for further investigation.

Tritium and carbon-14 from the plant can be detected in fruit and vegetables grown locally, and concentrations of tritium in flounder from the Severn Estuary doubled between 1999 and 2000. Excluding fish eaters, the Food Standards Agency says that children aged one to two get the largest dose in the local population, particularly from carbon-14 in cow's milk, though even this is well within safety limits. Rob Edwards

Fixing the script
Why replace genes when editing their messages works better?

A NOVEL form of gene therapy that repairs the templates cells use to make proteins could be used to treat genetic diseases and destroy cancers. The technique could one day even remove organs such as the prostate gland without surgery.

In animal tests, Intronn of Durham, North Carolina, and its collaborators have already shown they can fix the faulty templates to blame for cystic fibrosis and haemophilia. And they're using the technique to target and destroy cervical cancer cells.

For some disorders, the approach has seversal advantages over normal gene therapy. This involves adding extra DNA to cells to compensate for a faulty gene. However, the modified viruses usually used to shuttle the DNA into cells are too small to carry large genes. They also need to be targeted to the right cells. And the activity of the extra genes needs to be carefully regulated.

One promising alternlitive is to repair genes rather than add new ones (New Scientist, I I September 1999, p 14), but so far this is limited to fixing only one or two DNA 'letters' at a time. Intronn's technique, however, allows major alterations to be made.

It exploits the fact that each of our genes is interspersed with many regions of junk, or introns. After DNA has been transcribed to create "pre-mRNA", the introns are edited or spliced out to make the final mRNA-the template for making a protein (see below).

IntTonn has devised tiny slugs of RNA that it calls "pre-therapeutic mRNAs", or PTMS, that carry replacements for some of the coding regions in a gene, or exons. A PTM binds to pre-mRNA in such a way that during splicing, when introns are removed, the PTM exons replace the defective natural exons.

Crucially, PTMs affect only cells that "express' the target gene. If the gene in a particular cell is not churning out its protein product, there'll be no pre-mRNA from this gene to bind to, so the PTM will be harmless and inactive. "If our system gets into the wrong cells, the natural target is not there," says Gary McGarrity, the founder of Intronn.

Other attempts to edit pre-mRNAs using RNA enzymes haven't worked well because these sometimes bind to the wrong premRNAs (New Scientist, 15 June 1996, p 16). But the PTMs target a longer sequence on the pre-mRNA and so are more specific.

The approach also means you don't have to worry about regulating gene expression, since an excess of PTMs will make no difference. "Production of the protein would be regulated by the availability of RNA from the [cell's own] gene," says Dusty Miller of the Fred Hutchinson Cancer Research Center in Seattle.

He points out that this approach can help with genetic disorders where the problem isn't simply the lack of a working protein, but the production of a dangerous defective.?, protein. "For dominant genetic diseases like some collagen disorders, this is one of the few strategies that would reduce production of the defective protein," he says.

As with conventional gene therapy, though, delivering the PTMs is the biggest obstacle. At present, Intronn is using viruses to deliver DNA-from which cells make lots of PTMs-but it believes that PTMs could be small and versatile enough to be packaged and given as pills.

While people with hereditary conditions might prefer a permanent treatment to taking expensive pills, this would be fine for short-term treatments for cancer. With Carl Baker of the National Cancer Institute, near Washington DC, Intronn is devising PTMs that target pre-mRNA from the human papilloma virus, found in cervical tumours. Rather than fixing part of the gene, however, the PTM sneaks in the recipe for making diphtheria toxin, killing the cell.

The company hopes to create a range of PTMs that target genes switched on only in tumours or specific tissues. Andy Coghtan

Seized by God
THE Bible may contain the oldest recorded case of temporal lobe epilepsy. Ezekiel, the prophet whose visions are recorded in a book of the Old Testament, apparently had all the classic signs of the condition. Earlier this year Eric Altschuler, a neuroscientist at the University of California at San Diego, claimed that the Biblical strongman Samson may have been the earliest known sufferer of antisocial personality disorder (New Scientist, 17 February, p 19) Now he says that records in the Bible reveal that Ezekiel, who lived about 2600 years ago, showed extreme classic symptoms of temporal lobe epilepsy. People with the disease experience partial seizures, often accompanied by a dreamy feeling that things are not quite as they should be. Patients are often misdiagnosed with psychiatric problems. Neurologically, Ezekiel displayed some obvious signs of epilepsy, such as frequent fainting spells and episodes of not being able to speak. The Biblical figure, who chronicled the fall of Jerusalem in 586 BC, exhibited other peculiarities associated with the disease. For instance, he wrote compulsively, a trait known as hypergraphia. Altschuler points out that the Book of Ezekiel is the fourth longest in the Bible-only slightly shorter than Genesis. "It's impenetrable," he says. "He goes on and on." Ezekiel was also extremely religious, another characteristic associated with this form of epilepsy. V%rhile many Biblical figures are pious, none was as aggressively religious as Ezekiel, says AltschuleL Other signs of epilepsy can include aggression, delusions and pedantic speech-and the man had them all, Altschuler this week told a meeting of the Society for Neuroscience in San Diego.

Understanding that Ezekiel may have suffered from epilepsy helps put his writings into perspective, says Altschuler. "Once you appreciate that, you can see where he's coming from." It also serves as further evidence that this disease is genetic in origin. "If there were no old cases," he says, "we'd have to ask if there was something wrong in our environment." Alison Motiuk

The Song of Catastrophe
EARTHQUAKES, landslides, premature births, stock-market crashes and mass extinctions the more we find out about them, the more unpredictable they seem. For years, people have been trying to understand what triggers catastrophic events like these. Why, when everything is running smoothly, does disaster strike out of the blue? Are there really no warning signs that would let us take cover?

Most researchers have given up. They say these catastrophic events occur because the Earth's crust, financial markets and the world's ecosystems are all "critical systems"-always balancing on a tightrope. They are inherently unpredictable because it is unclear how they will react to a nudge: sometimes they keep their balance while at other times they topple off the rope. But Didier Sornette, a geophysicist who splits his time between the University of California, Los Angeles, and the CNRS in Nice, France, thinks they have given up too easily. He claims to have found a subtle underlying signal, common to many catastrophes, that can sound the alarm before it's too late. Until now, these whispers have gone unnoticed, but Sornette believes they could be the key to forecasting catastrophe. It's a hugely controversial claim, and has attracted criticism from experts in all fields where Sornette has touted it.

It began in the early 1990s, when Sornette was developing a theoretical model for predicting rupture in materials such as concrete, carbon fibres and certain metal alloys (Physical Review Letters, vol 68, p 612). He modelled the breakdown as a network of growing and interacting microcracks that finally result in rupture. Sornette found that the rate at which these growing cracks released energy was correlated with the time left before the material suffered catastrophic failure. In other words, the cracks-even the seemingly insignificant ones-give you a countdown to disaster. So that's the model, but would the same thing hold for real materials? Working with engineers from Aerospatiale, the French aerospace company, Somette stretched Kevlar and carbon-matrix sheets to cracking point in pressure tanks, while sensitive microphones recorded the pops and squeaks of the materials. Careful analysis of all the frequencies revealed warbling trills and rumbling bellows that no one had noticed before. "It was like suddenly being able to pick out the plucking of the double bass and the tinkling of the harp from the rest of the orchestra," says Sornette. "The secret was in getting a very clear recording so that nothing was muffled."

They repeated the experiment using all sorts of different materials, and the same pattern emerged every time. A little trill appeared at intervals in the recording, a bit like the chorus in a song. Except it grew higher and higher, with ever smaller gaps between repeats, until suddenly the material broke.

Sornette plotted these choruses against the time to failure, with the time axis on a logarithmic scale. Remarkably, they appeared to repeat at perfectly regular intervals so he called them "log-periodic' oscillations. By plotting three or more choruses he could use the intervals between them to predict how long it would be-or how much stress it would take-before the material suffered catastrophic failure. As the experiments progressed, Sornette became increasingly confident that he could accurately predict impending failure in materials. Aerospatiale patented the method, citing Sornette as one of the inventors, and used it to pressure-test the carbon-matrix tanks on the Ariane 4 and 5 rockets. After applying a constant pressure to the tank for a short time, software picks out the chorus in the cacophony of sound and gives a prediction of a tank's rupture pressure to within 3 per cent. "Sornette's method made a big difference to us," says Jean-Charles Anifrani, an Aerospatiale engineer who worked on the Ariane project. Anifrani is now chief engineer at Eurocopter, the world's largest manufacturer of helicopters, and has begun using the same idea to test helicopter gearboxes and parts of tail rotors. "Now we can predict the pressure at which the tail rotor tubes will rupture, and this means we can be confident that each tail rotor tube is capable of doing its job," he says. Sornette is not content to leave it there. Because it now looks as if predicting certain catastrophic events may be possible after all, he feels that he ought to be doing just that. He has, for instance, studied landslides to see what kind of tune they sang. First he and collaborators ftom the University of Grenoble, France, analysed laser measurements and seismic data taken before the 1987 slip at the Tinee Valley in southern France. It was ZE a fairly minor event and no one was hurt, but it did destroy a road, which had to be rebuilt on the other side of the valley.

The seismic data from the slip lived up to Sornette's expectations: there was his pattern-with the all-important chorus-well before the slip occurred. Sornette showed how the data could have been used to predict the timing of the landslide-to within a month-up to a year in advance.

Sornette has also looked at seismic data from landslides and rockfalls on the volcanic island of Reunion in the Indian Ocean. Once again, he says his method successfully predicted when the slips were due. "I am really encouraged by these results,' he says. "If I can verify the method on a few more landslides then I hope to start putting this work into practice." He believes he will be able to give enough warning to evacuate an area before a catastrophic slip occurs.

If seismic rumbles can predict landslips, what about earthquakes? Sornette has spent much of the past decade analysing seismic data from earthquake zones, and says we should be able to spot danger coming here too. But, he adds, it's not as straightforward as predicting landslides. "Identifying the relevant data really is a big problem here," he says. "Earthquake fault networks cover vast areas and we can never be confident which fault the big earthquake will choose to rattle." There are also problems in identifying the area over which to take measurements. But even if his method can't predict the timing and location of earthquakes, Sornette says it can at least provide an all-clear. While most researchers believe earthquake systems are in a dangerous state the whole time, Sornette claims that most of the time they're safe. He believes that earthquakes follow seismic cycles in which small and medium-sized earthquakes join up faults and create stress links across the whole fault network. Eventually all the faults become connected-the critical state-and a small slip anywhere in the network can lead to catastrophic failure. But until that state is reached nothing major will happen, and the area can be declared safe. After a large quake the stress correlation is destroyed and the whole process starts again.

This hypothesis cuts right across the received wisdom about earthquakes and similar catastrophic events. The orthodoxy says that there's no fundamental difference between the mechanisms behind differentsized cracks. Most researchers follow the model that crack networks in any brittle material-from a piece of concrete to the Earth's crust-are "scale-invariant" (New Scientist, 8 November 1997, p 30). Look at a stressed piece of concrete from half a metre away, and you might see a few large cracks per square metre. Zoom in with a microscope, and you'll see smaller cracks, but they'll look the same as the large ones: they have the same distribution over the area that you can see. Whatever the scale at which you look at the concrete, your view always appears the same. That means a large crack is just a small one that didn't stop growing (Science, vol 275, p 1616). And this, the sceptics say, is what sounds the death knell for predicting disaster: a big earthquake is simply a small earthquake that didn't stop. So, unless you're willing to panic every time the earth so much as shivers-and in earthquake zones it does that a lot-there's no way to get out of town before the big one.

However, Sornette thinks that many systems have a special kind of scale-invariance, called discrete scale-invariance, that might actually make it possible to spot a breakdown coming. Ordinary scale-invariance leads to a distinctive distribution of crack lengths: plot the length of a crack against the number of cracks of that length and you'll get a smooth curve with small cracks most common and big cracks least common. But from his analysis of real and model systems approaching catastrophic failure, Sornette believes a system under stress will actually show discrete scale-invariance. So, some crack lengths will occur more frequently than for an ordinary scale-invariance distribution. The details will be different for each system, but the signal data will always be peppered with subtle signatures-such as the log-periodic signals-that reveal when the whole system will go critical.

Sornette has begun looking at seismic data from the southern California fault system, including the famous San Andreas fault. From an initial study of the data, he thinks he can pick out a faint chorus signal among all the noise. What's more, the timing between seismic choruses has been diminishing fast recently, and the southern part of the California fault system may be just months away from the "critical state'. He thinks that California is gearing up for another big quake, measuring around 7.5 on the Richter scale.

But that doesn't mean Californians should be panicking around Christmas. The critical state is where the system is poised to failit doesn't mean that an earthquake will happen immediately.

Ian Main, an earthquake researcher at the University of Edinburgh and chair of a recent

set of Nature debates on earthquake prediction, feels that Sornette may be stretching a good idea too far. A block of concrete or the side of a mountain has clear edges to its fault network, he says. Earthquake zones do not. 'lt follows that it is harder to determine the location and maximum size of the next big earthquake in advance,' Main says. He is also concemed that Somette's interpretation of the data makes some artificial, arbitrary distinction between smaller and larger earthquakes.

Sornette acknowledges that a fault zone is not the same as a block of concrete, but he is undeterred. In fact, he reckons that logperiodic signals, and other indications of an impending critical point, will turn up in many different systems that undergo sudden, catastrophic changes. He even reckons they could help predict the timing of one of the most traumatic events any of us face: birth.

In this instance, the equivalent of the Earth's seismic vibes are the electrical signals given out by uterine muscle. Sornette wants to look for log-periodic signals in the muscle fluctuations, and translate them into a birth forecast. "I believe that this could be used to predict the day a woman will give birth and that I could recognise unusual signals such as that of a premature birth,' he explains.

'IT NOW LOOKS AS IF PREDICTING CERTAIN CATASTROPHIC EVENTS MAY BE POSSIBLE AFTER ALL'

'SORNETTE CLAIMS TO HAVE PICKED OUT CHORUSES HERALDING THE WALL STREET CMSH'

This claim has already caught the attention of Peter Bowen-Simpkins from London's Royal College of Obstetricians and Gynaecologists. Premature babies are usually much smaller, weaker and more likely to suffer from problems in later life. Many women are knownfrom past experience-to be at heightened risk of premature birth, so being able to monitor them and have advance warning would be immensely useful, says Bowen-Simpkins.

They might not be able to stop the birth, but they could act to give the baby the best chance of survival-steroids, for instance, to help mature the fetal lungs. 'This would significantly reduce the risk of breathing problems when the premature baby is born," Bowen-Simpkins says. And since the steroids can have serious side effects for the mother, he would welcome any test to see if and when they are necessary.

Sornette has collaborated with a team of Parisian obstetricians to produce a mathematical model of the triggers for birth. He modelled the various tissue layers of the uterus as oscillators. Before labour they are all unconnected and behave independently, he says, but as the layers of tissue mature, their behaviour changes. They start working together, in the same way that independent cracks in concrete grow and form networks. And because of that, a repeating chorus in the electrical signals from the uterine muscles should tell you when the organisation will be complete and labour is set to begin.

Sornette and the obstetricians have already done some preliminary experiments. They fitted pregnant women with an electronic belt that continuously monitored and recorded their uterine muscle activity. Initial results are promising, and there seemed to be a chorus, but logistical problems such as the uncomfortable design of the belts halted the experiments before they could gather enough evidence to tell for sure.

"The biggest difficulty is to find a sensible way of measuring the uterine contractions," says Bruno Carbonne from the Port Royal Baudelocque maternity hospital in Paris. "Currently we are investigating non-invasive methods such as using ultrasound." Once the problems have been ironed out, Sornette wants to restart the project, and is looking for more obstetricians willing to participate in a large-scale, long-term survey.

It's odd enough that the same patterns should appear in apparently unrelated natural signals, such as seismic data and muscle impulses. But Sornette believes that exactly the same patterns also turn up in man-made systems. And that's why he wasn't surprised to find his repeating choruses singing their way through the financial markets.

Sornette, working with Anders johansen of the University of Copenhagen, claims to have picked out the choruses heralding the Wall Street crashes of 1929, 1962 and 1987, as well as the 1997 crash on the Hong Kong stock exchange. He also heard the warning bells before the NASDAQ high-tech bubble burst in April 2000 and correctly predicted a sudden upturn in the Japanese Nikkei index for January 1999. "In some ways it seems surprising that the same theory works for epochs that are so different in terms of speed of communication and connectivity," he says. "What this may show is that the stock market has always been driven by human nature-and this hasn't changed so much." However, that's not enough to persuade James Feigenbaum, a physicist working in the Tippie Business School at the University of Iowa. He believes Sornette's vision of portentous periodic signals hidden in financial data could be fundamentally flawed. "It has not been convincingly established that logperiodic oscillations are absent from times where no crash is evident," Feigenbaum says. It's possible that everything-catastrophic or not-produces subtle log-periodic signals. Sornette is undaunted by Feigenbaum's observation: he believes he has been thorough in the statistical analysis of his data. 'I am confident that I am seeing a real log-periodic signal, and that in certain situations this can be used for predictive purposes," he says.

Yet the very fact that Sornette's theory is so wide-ranging worries many other researchers of critical systems. For them, the large number of phenomena which he claims will be predictable makes the whole thing seem just too good to be plausible, let alone [email protected] though so far no one has come out and told him flat that he's wrong.

Sornette is still working on his analysis techniques, unravelling new signatures from the data and working out new ways to model critical systems. And not everyone thinks he's following a false trail. "There may be some truth in Sornette's claims," says Neil Johnson, a director of the Oxford Centre for Computational Finance. "I do believe the answer to whether a large change is coming up may somehow already be encoded in the make-up of the system." Of course, Johnson warns, dramatic external events-such as the attack on America or a meteorite impact-can propel a system beyond the boundaries of predictability. But in the normal course of events, everything required to predict big changes could well be hiding within the data. All we need to do is find the right way of taking a diagnostic X-ray. "The question is: has Sornette found the right X-ray?" Johnson asks. "Only timeand an awful lot of testing-will tell."

Kate Ravitious is a science writer based in London Further reading: www.arxiv.org/abs/cond-mat/0107173 http://helix.nature.com/debates/earthquake

Forget the pharmacy
Ordinary foods are packed with substances that keep disease at bay, says Colin Tudge

SURELY the whole thing should have been sewn up long ago, it's been 300 years since British sailors discovered the value of limes for staving off scurvy, and the science of nutrition was born. Now there are charts and textbooks galore to tell us exactly what each of us needs each day, and why: energy, protein in all its forms, the many kinds of fats, the peculiar miscellany of essentials known collectively as vitamins, plus a catalogue of minerals that seems to include half the periodic table; all that plus dietary fibre. There is nothing to do now, it seems, but dot a few i's and cross a few t's. Wrong. On supermarket shelves and in the labs of multinational companies a quiet revolution is taking place. Bemused consumers are being bombarded with an ever-swelling range of products loaded with ingredients quite alien to standard nutrition texts. There are yoghurts containing the Shirota strain of the bacterium Lactobacillus casei, margarines containing plant sterols. Even everyday fruits and vegetables are being presented in a new light; for centuries regarded as "just food", they are now being rebranded as handy devices for delivering antioxidants or natural repositories of agents that have pharmacological effects over and above their role as conventional nutrients.

It is easy to be cynical, and regard these so-called functional foods and nutraceuticals as commercial gimmicks. Or worse, to view them suspiciously as medicines thinly disguised as food supplements, evading regulation and rigorous clinical testing-the modern equivalent of past centuries' snake oil. And in truth, the benefits are in many cases still contentious. Does tycopt!ne in tomatoes really reduce the risk of prostate cancer? The evidence is incomplete. Do plant sterols lower blood cholesterol? Some studies say yes, others no. Should we all be consuming "probiotics" so encouraging "friendly" bacteria to grow in our guts to protect us against disease? Again, the evidence is mixed. Yet there are sound scientific reasons for taking this revolution very seriously. These nutraceuticals may represent just the first foray into a whole new category of nutrients that lie somewhere between vitamins that we can't do without and toxins that we must avoid. Plants have evolved a host of chemicals to protect them from being eaten, and we, in turn, have evolved a tolerance to many of them. But evolution didn't stop there.

I believe that we may have turned many of these chemicals to our benefit, and that our diets are impoverished without them. Nutritional science so far is actually nothing more than a first draft. I suggest that we need to rethink the way we farm, cook and eat. Not only that, but viewed in the light of evolution, I think that many of the chemicals we think of as damaging drugs may well have hidden benefits. I arrived at these ideas by asking why we need even such well-accepted entities as vitamins. The answer is far from obvious. Vitamins are an extraordinarily mixed bag of chemicals, which complicate our nutrition no end. Our dependence on them seems bizarre: no engineer would design a motor with such an arbitrary list of extra requirements. Yet in a state of nature, vitamin deficiency does not seem to be a problem. How do we make sense of all this? Part of the answer, of course, is that human beings are not "designed" at all. We are not simple machines. We are innately messy because we have evolved. And because all creatures are constantly exposed to the presence and the importunities of others, we are permanently locked in what modern biologists call an arms race. Some of the fiercest battles are fought at the level of chemistry. Below ground, bacteria and fungi have been slugging it out for bil lions of years. We take advantage of this by creaming off an ever-increasing range of antibiotics, those organisms' principal arma ments. Above ground, animals slug it out with plants. All terrestrial animal life depends in the end on the consumption of plants; the plants, for their part, have to have ways of dealing with the onslaught of animals. To some extent they seek simply to outgrow the animals that prey on them. But plants also produce an array of spikes, fibres and hairs to make themselves unpalatable. In addition, most wild plants are toxic to some degree. Chemical warfare is expensive, metabolically speaking. If it were not necessary, plants would be able to spend their hard-won energy on making seeds, to spread their own genes. But like a beleaguered nation, they must invest heavily in defence. When animals eat the plants, as they must (or, if they eat meat, they rely on those that do eat plants), they in turn evolve detoxifying mechanisms. Koalas are the supreme detoxifiers. The leaves of eucalyptus, their only food, are steeped in toxins and noxious oils, all bound up in the toughest fibre. But the koala appendix takes the poisons in its stride. Here's the twist. Evolution is supremely opportunistic. Any organ or metabolic system that has evolved in response to any one problem is liable subsequently to be pressed into some different service. Natural selection would favour any individuals who could turn the costly detox mechanisms, or the residues that they produce, to some further purpose. For such organisms, detox would not just be a matter of cleaning up. it would become a positive bonus. Are there examples of such a progression, from negative to positive, that would make such musings more convincing? Indeed there are. Earth's earliest life flourished in an atmosphere that was almost totally devoid of free oxygen. Then, probably around 3 bil lion years ago, bacteria comparable to the modern cyanobacteria evolved a primitive form of photosynthesis, harnessing energy fr,om sunlight and releasing oxygen gas as a by-product. Photosynthesis works, and the organisms that could do it flourished. Suddenly, geologically speaking, the Earth acquired air rich in oxygen. Oxygen is extremely reactive. It rusts iron, it tums fats rancid, it makes fire. For creatures that did not evolve in its presence, oxygen is lethal. Natural selection would have favoured creatures that could detoxify this awful gas. All creatures that choose to live in the modern atmosphere contain a host of oxygen detoxifiers But that, of course, was not the end of the story. We may speculate that some organisms detoxifled oxygen by exposing sugars to it. The energy thus released was presumably wasted at first, as heat. Later, though, it was harnessed: used to create ATP, the universal currency of energy exchange. Thus was bom aerobic respiration. Oxygen, so lethal because it is so fiery, was put to good use. A similar process, I suggest, explains our reliance on vitamins. Some, at least, arose as toxins. Plants evolved the means to produce them because at first this kept animals at bay. Then those animals evolved detoxifying mechanisms in response. Later, the descendants of those first detoxifiers began to exploit the toxins themselves, or their breakdown products. These attempts to cope with plant toxins, I suggest, have left us with the need for vitamins. Now apply this notion more broadly. We know that plants between them produce an astonishing pharmacopoeia of recondite chemicals, often in the spirit of self-defence. What they do to us, or for us, depends on where we've got to in the arms race. A great many materials that plants produced as tox ins still poison us: here, the arms race favours the plants. At the other end of the spectrum are the vitamins that have become as vital to us as oxygen. Somewhere between the two extremes lie a host of pharmacologically active agents that affect us to some extent, but are not gener ally lethal except when taken in very high and unlikely doses, and yet are not absolutely vital either. These materials include all those that have long been recognised as "tonics": everything from camomile tea to ginsengindeed embracing a great deal of traditional herbal medicine. But also, near the vitamin end of the spectrum, is the growing list of beneficial but not absolutely vital materials that are now being classed as nutraceuticals or functional foods. Our bodies have come to terms with them, evolved ways of using them, but are not absolutely dependent.

If nutraceuticals are so important, why has it taken so long to discover them? Many reasons. In part, there's simply a lot to find out. Knowledge even of the recognised vitamins has been hard won. 'hie notion that lack ot folic acid in pregnant women might predispose to spina bifida has been verified only in the past few decades. (I attended a meeting in the 1970s at which doctors discussed the ethics of conducting a controlled study of the role of folic acid, given that its role in protecting fetuses was already strongly suspected). Nutraceuticals might be seen as .quasi-vitamins", with many obscure effects. It is good to lower the blood cholesterol, as plant sterols seem to do. But most of us live to reproductive age and beyond even if our cholesterol is higher than is ideal. It is a tribute to modern pharmacology that the effects of these plant chemicals have been noticed at all. A few extra years of life or a slight but significant improvement of mood, for example, would be even more difficult to detect. How much more is there to be found out?

Although specific tests have yet to be done, if the thesis is true then the implications are immense. To begin with, the host of companies now involved in nutraceuticals stand to make billions, and perhaps deserve to. They may be onto something big. Yet there are far broader implications. For the thesis suggests that human beings need a huge variety of chemicals that are made by plants and fungi and microbes that are as yet unquantified or even unsuspected. People gathering plants from nature achieved this in passing: a hunter-gatherer's diet typically included scores of species, most of them shot through with tannins, terpenes, alkaloids, oils, and all the rest. Modern diets are based on just a few domesticated plants which in general have been bred not for their biochemical variety but for yield and succulence. Biochemically speaking, modern crops tend to be far blander than their wild counterparts. In general, then, I suggest that modem, agricultural human beings, are 'pharmacologically impoverished': deprived of that host of quasi-vitamins that our physiology has evolved to make use of.

The real message, perhaps, is that we should revert to a more 'primitive', botanically far more varied, diet much closer to the diets not simply of our hunting-gathering ancestors, but of our pre-human ancestors. All the world's agriculturalists, both breeders and farmers, and indeed the world's chefs, should go back to the drawing board. Indeed, the whole of herbal medicine needs looking at again in the light of this idea.

We might also apply a little evolutionary thinking to the great [email protected] noire of our age: "drugs". Behind the official condemnation of opiates and cocaine, alcohol and nicotine, marijuana and caffeine-and the undoubted dangers that their misuse can pose-lies the largely unexplored conceit that "drugs' in general must be bad. Yet our brains, like our bodies, evolved in the presence of weird, extraneous materials made by plants and mushrooms. We know from experience that if we expose ourselves to some of them, we perceive the world differently.

Puritans, along with most modern lawmakers and medical scientists, feel that any deviation from the most unadulterated baseline in what we ingest is by definition abnormal. But our ancestors, gathering wild plants, must have been steeped in these recondite materials. Perhaps our brains work best in their occasional presence, just as our bodies work best in the constant presence of oxygen. Perhaps our brains, like the rest of us, are "pharmacologically impoverished'. Maybe there is survival value in looking at the world from different points of view at different times; perhaps the agents that we recognise and have often condemned as 'drugs" help us to do this. Many people with no criminal or otherwise pathological tendencies adjust the tenor of their lives by judicious intake of alcohol, caffeine and nicotine. Is it because they are .weak', as puritans have maintained, or because that's the way the human brain works best? Perhaps we should ask whether the current often hysterical war against 'hard" drugs is really appropriate-and I write as one with almost no exposure to any drug less respectable than Glenmorangie.

Only in recent years, 140 years after Charles Darwin laid out the idea of natural selection in On the Origin of Species, has it become fashionable to apply elementary evolutionary thinking directly to day-to-day human affairs. When applied to nutraceuticals, such thinking suggests that they are not mere hype. They could be the start of an even more exciting era in biology than we have yet realised.

Cotin Tudge writes about science. His latest books are In Mendel's Footnotes (from Jonathan Cape) and The Variety of Life (Oxford University Press)