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Addiction Vaccine

Experiments with rats and monkeys have already shown that an injection of antibodies can stop cocaine-addicted animals from seeking out the drug. The hope now is that this will help people who want to quit. 'This isn't a cure, it's fike a safety belt," says Michael Owens of the University of Arkansas for Medical Sciences in Little Rock. "For people who use it right, we think it will greatly reduce the chance they get hurt.' But potential misuse of the vaccine seems destined to trigger as much interest as its benefits. Barbara Fox remembers about six years ago, when her team at the Massachusetts-based company ImmuLogic presented their grant request to the NIDA for the cocaine vaccine now in clinical trials, it was tumed down flat. It was considered too revolutionary, and there were fears that it n-dght be used on people who hadn't given their consent. "They were worried it would be used coercively," says Fox, who is now at Addiction Therapies in Wayland, Massachusetts. Such fears don't surprise Peter Cohen, a doctor and lawyer at Georgetown University in Washington DC, who has written on the legal implications of vaccines against addictive drugs (Drug and Alcohol Dependence, vol 48, p 167). He thinks that American law would allow parents to vaccinate rebellious children like Billy against their will. "You don't need a law degree to see who is going to win that fight," he says. He is less concemed about the spectre of job applicants being screened for antibodies. "I doubt that would stand up to legal challenge," he says. But that doesn't mean companies won't try, he adds. The idea of targeting 'at risk" groups with an anti-addiction vaccine may have been one reason why the NIDA panel initially took fright, according to Charles Schuster, a former NIDA director now at Wayne State University in Detroit, Michigan. "I think someone called it a racist plot," he says. But many people are untroubled by such worries, says Schuster, and he suspects that a vaccine would have wide appeal. In the 1970s, when he was director of the drug abuse centre at the University of Chicago, Schuster was the first to show that anti-drug antibodies, in this case anti-heroin, could work in animals. 'When I published, I got calls and letters from parents all over the world saying would you please, please immunise my child," he says. And it's not just parents who think vaccines might be a good idea. Ali Fattom, a vaccine specialist at the Florida-based company Nabi, thinks that many kids would volunteer. Fattom recently asked the classmates of his 16-year-old son about their feelings towards an anti-nicotine vaccine. "Most of these guys say I'll take it first thing, because that would relieve the risk of experimenting with cigarettes and getting addicted," he says. But the ethical issues surrounding these vaccines run deep. "Should we be taking away people's pleasures?" asks John St Clair Roberts, medical director at the British company Cantab Pharmaceuticals, based in Cambridge, which took over Fox's vaccine programme from hnmulogic and now runs the clinical trials. "A person who gives up today might change their mind tomorrow," he points out. "But you can't tum off the immune system with a switch.' None of this will matter, however, unless the successes of the animal studies can be translated to humans. And this is far from certain-not least because researchers don't yet understand exactly how these vaccines work. Indeed, the approach was all but abandoned shortly after Schuster's pioneering work in Chicago. The work began when a colleague pointed out a newly developed antibody treatment for accidental overdoses of the heart medicine digitalis, which worked by binding the drug safely in the blood. Schuster and his team began to wonder whether it might be possible to treat heroin addiction in the same way.

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Constant cravings

The idea seemed straightforward enough. A major problem for recovering addicts is relapse. After a period of abstinence, they succumb to a craving for their drug and take a hit. But that taste only reinforces a greater hankering, and starts an ugly cycle of treatment and relapse. Schuster reasoned that because antibodies are too big to cross the blood-brain barrier, any drug they grabbed would be kept safely away from the brain. To test the idea, Schuster and his team created a vaccine by chemically joining a heroin-like molecule to a protein that they knew would be detected by the immune system and stimulate antibody-producing cells. Next, they inoculated heroinaddicted rhesus monkeys that had been trained to self-administer by hitting a lever which injected heroin straight into their blood. Their results were dramatic. At the peak of the vaccine's effectiveness, inimunised monkeys found heroin no more alluring than a salty water control (Nature, vol 252, p 708). But despite this success, there were major drawbacks. in par ticular, the animals had to undergo a brutal inoculation regime several times a day for weeks for the vac cine to be effective, which caused ulcers to form at the site of the injection. The researchers were also disappointed that the monkeys' antibody levels seemed to drop wiffiffi a few weeks, and that as the drug dose was raised, the anti bodies became saturated, and the animals resumed their heroin habit. The approach was all but aban doned shortly afterwards because, on top of these problems, it faced competition from other methods of treating heroin addiction. It was around this time that other groups were reporting excellent results using chemicals such as methadone and naltrexone, which block the action of heroin by competing with the drug for special receptor sites in the brain. 'Everyone became convinced that the true salvation for addicts everywhere lay in this "small chemical" therapy. One reason they seemed a better bet was that their molecules are similar in size to the drug they are countering, so they could be given in doses equal to or greater than the drug, while antibodies, being large molecules, seemed easier to outnumber. It was nearly 20 years before researchers seriously reconsidered the vaccine idea, and for a simple reason: desperation. No drug had emerged to treat cocaine and its use was reaching new heights. Then a pharmaceuticals company asked Kim Janda at the Scripps Research Institute in La jolla, California to develop a vaccine that would stimulate animals to produce antibodies which could be used in a cocaine screening test. To Janda's surprise, the vaccine his team created dramatically blunted the psychoactive effects of cocaine in rats, halting the hyperactivity and sniffing that the drug usually inspired (Nature, vol 378, p 727).

As it tumed out, Fox and her colleagues at ImmuLogic were right on Janda's heels, having decided to take a gamble on a cocaine vaccine of their own. They soon reported that immunised rats would stop self-dosing cocaine, much as Schuster's monkeys resisted heroin (Nature Medicine, vol 2, p 1129). Advances in vaccine design meant that the treatment worked after just a small number of injections, and caused no ill effects. So ImmuLogic pushed ahead with clinical safety trials, ultimately selling the rights to Cantab. The British company recently reported that there were no adverse reactions among the 34 recovering cocaine users who participated in the study. All produced substantial levels of antibodies to cocaine-, and in three of the participants, antibodies could be detected a year later. With the prospects for Cantab's cocaine vaccine looking promising, other labs have gone on to investigate the effects of vaccines on other addicfive drugs. For sheer numbers, the most impressive must be the study reported this February at the Sixth Annual Meeting of the Society for Research on Nicotine and Tobacco in Arlington, Virginia, by Fattom and his colleagues. Over one week, they infused rats with a dose of nicotine equivalent to 1400 cigarettes, together with antibodies against nicotine. They then stopped the nicotine infusion and looked for the characteristic signs of nicotine withdrawal, such as chattering teeth, gasps and tremors. Even after this enormous dose, the symptoms were reduced by half relative to unimmunised controls. At a more realistic nicotine intake rate, the antibody was completely protective. This is encouraging evidence that the vaccine might not only help people give up cigarettes, but could stop others from becoming addicted, says Fattom. Other researchers have shown that vaccines are effective at blocking the effects of PCP and methamphetamine. The success of these animal experiments might suggest that the ability of antibodies to mop up the drug is now beyond doubt. But things are not that simple. Fox's group, for instance, showed early on that 30 seconds after a dose of cocaine, the brain concentration of the drug in immunised rats is reduced by only 30 to 63 per cent. So it is still at a level that would have given an unimmunised animal a rush. "The paper calculation tells you it shouldn't work," says Fox. "But the animal behaviour data tell you it does. So the question is why." There are at least two ideas in circulation. C)ne is linked to the notion that a drug's addictive effect is related to the speed at which it enters the brain. Cocaine is more addictive when smoked as crack than when snorted because the lungs have a larger surface area than the nose. So for the antibody to work, it might not need to hang on to the drug, just slow its progress to the brain. By contrast, the negative or "dysphoric" effects of cocaine such as anxiety and nausea seem to come from its final concentration in the brain. So antibodies might take away all the good effects of cocaine and leave only the bad. Owens has other data suggesting that antibody therapy ends up targeting the brain selectively. His lab has done extensive work on the kinetics of PCP interactions in the brains of rats. VVhen the researchers infuse the animals with extremely high doses of purified anti-PCP antibodies, the brain concentration of the drug drops to zero, even though levels remains high in other parts of the body (The Journal of Pharmacology and Experimental Therapeutics, vol 292, p 831).

Mind-altering

Owens suspects that PCP wouldn't have the psychoactive effects it did if it wasn't able to penetrate the blood-brain barrier rapidly. This may explain why a little bit of antibody works far better than expectedit mops up the drug in the blood vessels and the resulting drug diffusion gradient causes the drug to leak rapidly back from the brain into the blood vessels. "If one organ is preferentially protected, isn't it wonderful that it's the brain?" says Owens. But even given immunotherapy's mysterious success, researchers are eager to improve on it further by changing the method of immunisation. Inoculation with a vaccine, made from a drug linked to a protein, causes active immunity, a natural antibody response which triggers the body to produce a wide array of molecules with varying abilities to grab the drug. It's a method that can remain effective for a few months to a couple of years. By contrast, the animal can also be given passive immunity by infusing it with monoclonal antibodies, a single species of molecule produced from an antibody-producing cell cultured in the laboratory. Monoclonals can be selected to have very specific properties, such as very tight binding of the drug, but they are short-lived, lasting just a few weeks. In a paper just published (Proceedings of the National Academy of Sciences vol 97, p 6202), Janda describes how he has combined the active and passive approaches to deliver what he calls a "one-two punch". The vaccine alone is able to stop rodents from self-administering the drug until high doses are available. But with monoclonals included, even doses equivalent to three hits of cocaine are blunted and the animals stop pushing the lever after a few tries. janda compares the natural antibody response to a group of workers of varying strengths trying to capture the drug. But the monoclonal antibody is in a different league: "It's like sending in Superman to help," he says. At Columbia University in New York City, Donald Landry and his colleagues have even found that some monoclonals can destroy cocaine molecules. His team developed these "catalytic" antibodies by creating a vaccine that mimics cocaine's "transition state", a fragile form of the molecule which breaks down into [email protected] nine methyl ester, or EME, and ben zoic acid-which aren't toxic or psychoactive. They used the vaccine to isolate monoclonal antibodies that bind to the cocaine and twist it into its fragile state, making it more likely to snap apart (see Diagram). This ability to break down cocaine seems to give the antibody extra potency. For one thing, the broken fragments just slip away, leaving the antibody free to work again. At concentrations at which a comparable cocaine-binding anti body had no effect in rats, Landry's catalytic antibodies increased the lethal threshold for cocaine three fold and also dramatically blunted self-dosing of cocaine by addicted animals (Proceedings of the National Academy of Sciences, vol 95, p 10 176). The vaccines are at last looking as though they might be a more promising treatment than the small chemicals. Antibodies don't mess with brain chemistry the way blocking drugs do, so there should be fewer side effects. And antibodies are expected to be long-lived-from weeks to years-compared with a single day for a dose of naltrexone. "Right now, an addicted patient has to ask themselves every day if they should take their medicine or get high," says Colin Brewer of the Stapleford Clinic in London. "If they only have to make that decision every few weeks, it would be a great relief." He thinks antibodies would be a big help to recovering addicts who have trouble sticking with their therapy Researchers are confident they can push the vaccine technology even further. And they have another reason to be optimistic. It's only anecdotal, but the story is often told of two men from the Cantab trial who started doing hits of cocaine after their treatment-to no avail. One experienced nothing from the drug, the other felt his heart race, but didn't achieve a high. Tom Kosten, a psychiatrist at Yale University who conducted the trial, says that if this anecdote foretells that effective immunotherapy is possible, then he, for one, will gladly confront the moral and medical morass that will follow. "hi my thinking," he says, "if we have a real vaccine to argue about, we would be very lucky."

Anthropic Controversy

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THE UNIVERSE is the way it is because if it weren't we wouldn't be here to see it. Profound insight or empty truism? This is the "anthropic principle", and in the past few years it has been embraced by many cosmologists to explain some of the most mystifying features of the Universe. But it leaves other scientists feeling deeply troubled. One of them is cosmologist Paul Steinhardt of Princeton University in New Jersey, who claims that the anthropic principle is sloppy and unscientffic. "It's corrupting science," he says. His view is shared by physicist Gordon Kane of the University of Michigan in Ann Arbor, who believes that string theory will make the anthropic principle redundant. The proand anti-anthropic camps are debating just about the most profound question there is: why are we here? But the final answer might not please either side. What makes the debate more difficult is that a precise definition of the anthropic principle is hard to come by. Roughly speaking, it asserts that our existence restricts the possible values of any physical constants, because simply to be observed, the Universe must allow life to exist. If we assume that life anywhere in the Universe must be broadly like that on Earth, for example, the Universe must allow stars to form. And the Universe must be old enough for those stars to have created plenty of heavy elements-the building blocks of biological moleevolve. Fred Hoyle was the first to In 1952, he used the fact that t carbon-12 had an 'excited" energy state unknown at the time. If the state did not exist, Hoyle reasoned, nuclear reactions inside stars could not assemble carbon and all heavier elements from lighter nuclei and so carbon-based life such as ours would not exist. The principle has gained popularity because of the apparent fine-tuning of physics. For'example, if the strong nuclear force were just a few per cent stronger, the Sun would burn all its hydrogen fuel in less than a second-not long for intelligent life to evolve. "Many instances have been found in which if a certain fundamental force were slightly weaker or stronger, or if a certain fundamental particle were slightly lighter or heavier, there would be no galaxies or stars or planets, and hence no human beings," says Max Tegmark of the University of Pennsylvania. Martin Rees of the University of Cambridge agrees: "I think the fine-tuning 'coincidences' need some kind of explanation." "Either God fine-tuned the Universe for us to be here," says Tegmark, "or there are many universes, each with different values of the fundamental constants, and not surprisingly we find ourselves in one in which the constants have the right values to permit galaxies, stars and life." Some have dubbed this the "multiverse". Inflation, one theory that aims to describe the first split second of existence after the big bang, hints that the observable Universe may simply be one bubble among an infinity of others in a vast ocean of space. Conceivably, the other universes might be distant patches of space where the fundamental constants are different. Tegmark believes that the anthropic principle is becoming more widely accepted. "Two years ago, at a conference at Fermilab there was an audible hiss when someone mentioned the A-word," he says. "But a couple of months ago at another conference in Santa Monica, Steven Weinberg argued that the anthropic principle may be the best explanation for the cosmological constant."

'Will the physics of the inflationary era indeed predict multiple big bangs, and do the underlying laws allow the different big bangs to be governed by different physics?"

The cosmological constant, which is a measure of the curious repulsive force exerted by empty space, is an embarrassing 10123 times smaller than that predicted by quantum theory Weinberg explains this by assuming that the constant takes on all possible values in all possible universes. Most universes would accelerate madly (where the constant is large) or make nothing but black holes (where it is large and negative). Only in a few freak universes where the constant is tiny would galaxies, stars and planets arise. So why does Steinhardt so vehemently oppose the anthropic principle? "I have several reasons," he says. "First, the anthropic principle is not testable, which means it is not science." According to Steinhardt, a statement has scientific meaning only if it can be tested by an experiment or observation. He maintains that there is no such test for the anthropic principle. "This makes it entirely different from, say, Newton's general principle that the laws of physics are deterministic," he says. "This was tested and found to be false in the realm of the atom." Tegmark, however, argues that the anthropic principle is no more sophisticated or controversial than the principles of logic that underpin a statement like 1 + 1 = 2. "If I have two competing theories, the anthropic principle merely selects the theory which gives the greatest likelihood of seeing what I see, given that I am here," he says. "The anthropic principle is no more than an application of probability theory Unfortunately, the word'principle' suggests there is something deep about it. In fact, there's nothing to test." But Steinhardt has a more telling criticism. C)ne of the characteristics of science, he says, is that you begin with a little and get out a lot. It's an efficient way of gaining knowledge. "What does the anthropic argument get you? I'm not sure there's enough to fill the back of a postage stamp." Take the cosmological constant. The anthropic principle seems to provide a rational explanation for why this constant has the value it has-but does that really tell us anything? Isn't it just a way of feeling comfortable with the way the Universe is? Contrast this with Newton's law of universal gravitation. Newton developed his theory to explain the orbits of the planets in our Solar System, but it has many other observable consequences-it predicts the existence of lunar tides and the movements of comets, moons, asteroids and other stars. So is the anthropic principle a useless but essentially harmless idea? Steinhardt thinks it's worse than that. He says it "dulls sharp problems with an air of explanation" it stops people from struggling to find really fundamental solutions. He sees its increasing popularity as partly due to impatience. "People want to know all the answers right now, but we have to accept that this is not possible," he says. 'I'd rather say 'I don't know'." Another serious objection to the anthropic principle is that "there are no rules of the game", says Steinhardt. He points out that there is no justification for the behef that physical constants vary from one universe to another. The problem, he says, is that there is no underlying 'metatheory" which predicts how they vary. We know that some parameters, such as the distance between the Earth and the Sun, can vary. Before Newton, there had been high hopes that this distance would turn out to be a fundamental constant, perhaps fixed by the geometry of cubes and other solid figures. However, Newtonian dynamics allowed a whole continuum of Sun-Earth distances. This is a little like the sort of metatheory that Steinhardt is talking about. For life to exist on Earth, the Earth must be neither too cold nor too hot-so we shouldn't be surprised that the Earth-Sun distance is just right for water to flow on the Earth's surface. But even this application of the principle is flawed. "Even now we cannot say how common planets are, or whether planets need to be like ours to foster life," says Steinhardt. For instance, if silicon-based machines could evolve, they might find themselves on a planet closer than Mercury is to the Sun. If it tumed out that life could exist in a huge range of physical environments, we would find ourselves in the special position of being cool, watery, carbon-based observers. The anthropic principle would lose its power. But in the case of the cosmological constant, says Steinhardt, there isn't even a theory predicting that it can take on a range of values. He maintains that such a theory, like Newtonian dynamics, would be bound to have other consequences-perhaps in the microscopic world-which could be measured. "If there's a breakthrough and the anthropic people can come up with an abundantly predictive, testable metatheory, I would be happy to accept it." Rees believes that such a metatheory could come from Andrei Linde's idea of etemal inflation. In that model, space spontaneously "inflates" to give birth to new universes, which give birth to yet more universes, and so on, ad infinitum. "There are two key questions for 21st-century physics/cosmology," he says. "When we understand the physics of the inflationary era, will it indeed predict multiple big bangs, as in the simulations of Linde and his colleagues? And do the underlying physical laws allow the different big bangs to end up governed by different lowenergy physics?" According to Rees, if the answer to both these questions is "yes", then anthropic selection would explain the apparent fine-tuning in our Universe. Tegmark would like to see this fine-tuning quantified. He believes that scientists have not performed such calculations because of "anthropophobia"-the principle makes them uneasy. The build-up of heavy elements inside stars, for example, depends on the electromagnetic and strong coupling constants, which determine the strengths of the electromagnetic and strong nuclear forces. "If someone calculated the detailed consequences for stars of varying these parameters, we could find out how small is the island in parameter space we live on," he says. That would tell us just how finely tuned the Universe is. Rees adds that if we found ourselves living on a highly improbable part of this island, that would invalidate the anthropic principle.

Useless speculation

All this may be useless speculation, however, because there are reasons to believe the constants can't vary. "I would say the examples of fine-tuning people have found aren't really there," says Steinhardt. He cites Grand Unified Theories (GUTs), which attempt to unify the three nongravitational forces of nature. In GUTS, the strengths of the electromagnetic and strong nuclear forces are intimately linked. "If you vary one, the other changes too," says Steinhardt. So the argument that all the constants must be individually fine-tuned begins to look shaky. Kane agrees: "It's simply not so that increasing the strong force or decreasing the electromagnetic force affects how the Sun works," he says. "Most of the old arguments are just misleading numerology." Kane believes that string theory provides even more powerful arguments against finetuning. In string theory, the fundamental entities of reality are tiny strings vibrating in 9-dimensional space, and all the constants of nature depend on a single fundamental parameter. "So if the theory is right there will be no room to vary any of the constants the anthropic people like to vary," says Kane. He and his colleagues, Malcolm Perry and Anna Zytkow of the University of Cambridge, have just written a paper [email protected] this argument, titled "The beginning of the end of the anthropic principle". But string theory does allow the vacuum to adopt a range of different states in different universes, which should, for example, have different cosmological constants. "In a sense, the ensemble of universes is replaced by something with a better theoretical basis, the many vacua of string theory," admits Kane. "Different vacua will lead to different universes, and only some will be right for life to emerge." So have string theorists, in rejecting the anthropic principle for a final theory, let it in by the back door? Is string theory the metatheory that Steinhardt is looking for? "Sure, superstring may some day prove to be a metatheory with lots of predictive power," says Steinhardt. "But I don't think Newton's theory or string theory include the anthropic principle-I think they replace it." Kane is also dubious. "Until the vacuum structure of string theory is understood better, it looks a lot like the multiple universes, but not the same," he says. That's because the various regions might be causally connected, affecting each other's states. For his part, Tegmark is sceptical of string theory. "It is emerging as the modern version of the emperor with no clothes," he says. "So far, it has predicted the value of none of the physical constants, and I'm willing to bet that numbers like the electromagnetic coupling constant will never be derivable from pure math." "Is he serious?" responds Steinhardt. "Where can we line up to take that bet?" But if Steinhardt wins the bet, the consequences may be uncomfortable. The theorists hope that string theory will be mathematically inevitable-the only logically consistent theory of the Universe. But if so, and if string theory pins down every physical constant, then the fine-tuning for life will turn out to be hard-wired into mathematics. "In that case, string theory will be a great argument for design," says Tegmark. He is reminded of Carl Sagan's novel, Contact, in which mathematicians calculate Tc to billions of decimal places and suddenly find the digits getting nonrandom. "It turns out there is a message written in a fundamental constant of mathematics-a message from the Creator," says Tegmark. Likewise, if the mathematics makes bfe inevitable, people might start using string theory as an argument for the existence of God. String theorists believe they are following a path to an ultimate rational theory that is a cut above the anfliropic altemative. They might be upset, to say the least, to find God in their equations. El

Further reading: Just Six Numbers by Martin Rees (Weidenfeld & Nicolson, 1999) The Anthropic Cosmological Principle by John Barrow and Frank Tipler (Oxford University Press, 1988)

Methane munchers go slow

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THE rise in atmospheric carbon dioxide predicted for this century could blunt the appetite of soil microbes that consume a large chunk of atmospheric methane, adding to the greenhouse effect, claim researchers in North Carolina. In dry soils, "methanotrophic" bacteria consume about 10 per cent of the atmosphere's surplus methane each year. In places where methane is produced, such as wetlands, methanotrophs consume huge quantities of methane before they ever reach the atmosphere. Researchers from the University of North Carolina in Chapel Hill and at Duke University in Durham studied methanotrophs in dry forest plots by exposing them for three years to twice the normal level of C02 When they then analysed samples from the soil, they found that methanotrophs were munching only about half as much methane as their counterparts from soil exposed to normal C02 levels. Rebecca Phillips of the University of North Carolina, who presented the work at the conference, says the team was not expecting such a dramatic decline. The microbes were not affected by factors such as water and nutrient levels, she says, so some as yet unidentified detrimental effect on the microbes themselves seems to be to blame.

Although less plentiful than C02, methane is 25 times as potent as a greenhouse gas. If similar results are found in other methane production sites, she says, the effect could have serious implications.

Gene smuggler

A CUNNING way of sneaking genes into the brain should make it easier to give people gene therapies for diseases such as Parkinson's and Alzheimer's. The brain is protected from potentially dangerous substances in the blood by the tight junctions between capillary cells. Only recognised molecules are allowed in, so to get genes into the brain, researchers either have to inject them through holes drilled into the skull or give them intravenously along with drugs that disrupt the blood-brain barrier. Now William Pardridge and Ningya Shi at the University of California School of Medicine in Los Angeles have found a way to trick the barrier into letting therapeutic genes through while still protecting against harmful substances. The researchers first packaged the genes inside a fatty sphere called a liposome. Pardridge and Shi then tethered this package to an antibody that latches onto receptors on the brain's capillary cells and tells the cells to let the package into the brain. "It piggybacks through without interfering with the endogenous transport system," says Pardridge. When the researchers injected a package containing a gene for luciferase into rats' bloodstream, they found the protein appeared throughout the animals' brains. Their results will appear in a forthcoming issue of Proceedings of the National Academy of Sciences. "This approach is intriguing, and a potentially useful means of distributing genes widely throughout the brain," says Mark Tuszynski, a neuroscientist at the University of California, San Diego. Pardridge says they have already developed antibodies for primate receptors that could work in humans. Nell Boyce

Dawn of crops

AGRICULTURE wasn't invented in the Jordan Valley, but 800 kilometres to the north on the borders of Syria and Turkey, say Israeli scientists. Recent genetic evidence from wheat and lentils shows that edible plants were first domesticated somewhere within a 200-kilometre circle on the upper reaches of the Tigris and Euphrates rivers. Some researchers have proposed the Jordan Valley and adjacent areas as the "cradle of agriculture", says Simcha LevYadun of Israel's Agriculture Research Organization. But Lev-Yadun and his colleagues have a different theory. They say that recent evidence shows that all seven crops important to ancient civilisations-einkorn wheat, emmer wheat, barley, lentils, peas, chickpeas and bitter vetch-originated in a small area on the borders of modern Syria and Turkey. And the latest research shows that modern-day cultivated lentils derived from a wild variety found only within this area. This fits well with archaeological evidence, which shows agricultural technology diffusing from the north to the south, Lev-Yadun says. "The evidence is consistent with their thesis," says Jerrold Davis, a plant biologist at Cornell University, Ithaca. But he cautions that some crops might have been domesticated from wild varieties living in regions from which they have since disappeared. Kurt Kleiner

Source: Nature (vol 288, p 1602)

Farming Diversity: Poverty and corruption are rapidly destroying the great tropical rainforests. Setting up reserves will only rescue a few fragments. Could farming and mining prove the real saviour?

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THE WORLD'S great rainforests as we like to picture them from television documentaries will soon be gone. Many people fondly imagine the forests' vast size and ahnost sacred ecological status will buy them enough time for environmentalists to work miracles. They should take a look at the international plan to "save" the world's largest rainforest, the Brazilian Amazon, which was clinched last month in Brasilia. After ten years of discussions with Westem governments, Brazil agreed to preserve just 10 per cent of the forest that remains in return for cash from the World Bank's Global Environment Facility. At the same time, the Brazilian Congress was considering plans to loosen legal controls on the development of other parts of the Amazon. Already, more than 50 per cent of the world's tropical forests have gone (see Graph). Asia has lost 88 per cent of its natural forest. Throughout the 1990s, rainforest losses averaged 1 per cent a year. Not only do we have to worry about losing rare species, a cascade of other enviroronmental consequences frequently follow the disappearance of forest, including changing climate, the spread of insect-home diseases like malaria, soil erosion and flooding. That's why the pessimism felt by observers such as Frederic Achard, coordinator of an European Union survey called Tropical Ecosystem Environment Observation by Satellite is so alarming. 'The pressures to remove the forests are too great to be stopped in many places," he says. According to Cambridge forestry scientist Tim Whitmore: "Southeast Asia has had it. Perhaps parts of Papua New Guinea can be saved, but not much else. A report to be released later this month by 'the EU and the World Wide Fund for Nature, after much prevarication, underlines the huge dffficulties facing campaigners and governments in their bid to halt the eradication of virgin tropical forest. It claims that countries have been forced to chop down their forests to raise cash to pay off intemational debts. The same report also names 11 countries (six in Central Africa) where foreign companies have bribed their way to lucrative logging concessions. The authors recommend banning all logging until the corruption had been rooted out. And while crooked bureaucrats get rich, the destruction continues. This week the World Bank is likely to join a $3 billion oil industry project to drive a pipeline for a thousand kilometres through the virgin forests of Cameroon to tap a huge oilfield in landlocked southem Chad. The Bank says the project could transform the economies of both countries. Critics say it will bring loggers and miners and bushmeat traders and a mess of squalor masquerading as economic development to a region occupied by indigenous hunters. But there is another way of looking at the situation-the view of rainforest realists or pragmatic protectionists. They say a detailed examination of how and why forests fall could, if nothing else, mitigate the damage to the global environment.

The two biggest causes of forest destruction are logging and clearing land for farming. The combination of both gave Cameroon the fastest deforestation rate in Africa in the late 1990s. Other factors come into play Civil wars in West Africa and the collapse of urban economies in Asia have triggered invasions of the rainforest in recent years. Even pofiticafly stable developing countries point out that most rich nations started out on the path to prosperity by plundering natural resources. Why should they be denied the same kick-start when they are so poor? Some envirorunental economists even say that some forms of development could be a boon to rainforest conservation precisely because they stand to replace logging as a source of income. Their list includes mining, oil drilling and some heavy industry. "If countries generate income from these activities, which don't use much land, then they don't need to grow their own food. They can import instead," says William Sunderlin of the Center for International Forestry Research in Bogor, Indonesia. Equally, oil exports in particular bump up the value of local currencies so much that timber exports, for instance, become uneconomic. Sunderlin sees strong evidence of this in a comparison of two Central African countries. "hi Cameroon, they chop down forests to make money from timber sales and to clear land for farming. In neighbouring Gabon, where their exports are dominated by oil, there is much less deforestation." Some 85 per cent of Gabon is still rainforest, one of the highest percentages in the world. Belying its poor envirorunental reputation in Ogoniland in nearby Nigeria, oil company Shell is running an envirorunentally friendly oil extraction business in the forest, advised by the WWF. Poor farmers move to jobs on oil rigs or in the cities rather than chopping down the rainforests. Equally some scientists argue that we should not be obsessed about protecting virgin forests. Many farmers are growing their own trees-including some indigenous varieties on land that was once virgin forest, in order to harvest wood, bark and fruit. Several studies suggest that because of this, tree cover may actually be growing in tropical regions as varied as West Africa and Pakistan. Recently, Qureish Noordin of the Kenyan Forestry Research Institute took me to the highlands of Western Kenya, where population density sometimes exceeds a thousand people per square kilometre, but still tree cover is growing. "As farms become smaller, farmers want to grow more trees because they are more profitable than crops like maize," he said. In his nursery at Maseno he showed me dozens of tree species grown by local farmers for fruit and medicinal products like bark. "People used to go into the forests to get them, but now they grow them on their farms," he said.

But many green campaigners are abandoning hopes of a synergy between environment and development. While some forests pay their way through an upsurge in eco-tourism, elsewhere the destruction continues. The much vaunted "extractive reserves" of the Brazilian Amazon, where communities would gather fruit and nuts without destroying the forests, have failed to catch on. In some quarters there has even been an upsurge of interest in old-style conservation-buying up pristine rainforest to preserve it. The Nature Conservancy, based in Arlington, Virginia, has a billion-dollar war chest for worldwide wilderness purchases. But most observers feel that on the whole, the economic pressure on the developing world to exploit rainforests is irresistible. The position taken by Western governments and corporations can be contradictory. In South America Guyana has dedicated a large tract of rainforest at lwokrama to a science-based study of conservation, but last month agreed to hand over 400 square kilometres of swamp forest for a US-run rocket launch pad (New Scientist, 3 June, p 5). Similarly, the EU is funding rainforest conservation in Cameroon. But at the same time it's paying for the construction and rehabilitation of some 2000 kilometres of roads within the country that are bound to make it easier to invade the forests. David Brown of the Overseas Development Institute, London, is crifical of the pressure being applied to developing countries by WWF and others, which is seeing them set aside preserved areas that they were not able to protect. He believes that governments will make more progress in conservation if they stop trying to centralise control of forests and instead give effective property rights to the people who live in them. Only then will forest dwellers have an incentive to protect the forests from over-exploitation. The best that can be hoped is that forests will prove of real value to their residents or provide them with important economic or ecological services, such as flood protection, so they can be saved from short-term plundering. But the truth seems inescapable: The vast majority of virgin tropical rainforest is doomed. The WWF's African forest coordinator, Wale Adeleke, admits that in the future, conserved areas will probably not exceed 10 per cent of what we have now. "Indeed it is not rational to require Africa to protect larger areas than the developed countries are prepared to set aside themselves," he says. This all leaves formal conservation strategies, which hinge on national parks and reserves, looking as substantial as the prisfine, emerald preserves we like to think they'll maintain. Fred Pearce