At least, this is what Shing-Hwa Liu and colleagues at the National Taiwan University in Taipei discovered when they exposed beta and islet cells to methyl mercury at levels typically found in contaminated fish (Chemical Research and Toxicology, vol 19, p 1080). Methyl mercury is a powerful oxidant, and this seemed to explain the effect: Lui's team was able to protect the cells from damage by adding the antioxidant N-acetyl cysteine.

Diabetes is on the rise in many countries, and has doubled in the US over the past 30 years. While obesity is thought to be the major cause, suspicion is also falling on pollutants. In July, a South Korean team revealed a connection between persistent organic pollutants and diabetes. They found that people with diabetes tended to have elevated concentrations of pollutants including dioxin in their blood, although they have failed to find any link with mercury.

Vivian Fonseca, a diabetes specialist at Tulane University in New Orleans, points out that very little of the methyl mercury found in fish actually makes it into the human bloodstream, which means the Taiwanese findings could overestimate the risk to human health.

"There might be many chemicals besides methyl mercury which kill pancreatic cells in experimental settings, but might not cause diabetes in humans," says Duk-Hee Lee of the Kyungpook National University in Daegu, who led the South Korean study on persistent organic pollutants. Liu agrees that researchers will need to carry out further studies in humans to confirm a link between mercury and diabetes. However, he has already discovered that mice fed low levels of methyl mercury for just a month produce less insulin, have higher blood glucose levels and sustain more oxidative damage to their fat cells.

"I think people should eat less fish," Liu says, restricting themselves to perhaps two servings of fish a week.

Lee's studies have also shown that the links between pollution and diabetes can be subtle and complex. In people in the US, blood concentrations of persistent organic pollutants have declined over the past few decades. However, Lee's team found that the association between diabetes and levels of pollutants in the blood was strongest in obese people (Diabetes Care, vol 29, p 1638). This may be because pollutants like dioxin are retained more readily in fatter people.

Fonseca argues that the epidemic of obesity is the main reason why more and more people are developing diabetes, but agrees that pollutants may be a subsidiary factor. "Additional factors such as pollutants may be playing a subtle role in some individuals," he says.

From issue 2571 of New Scientist magazine, 30 September 2006, page 18

Lying back, exhaling: usually the last thing a person does before leaving this world. Only in this case it is the world that is leaving me.

A few minutes ago I smoked a pipe of Salvia divinorum, a powerful hallucinogenic herb that I bought openly and legally from a shop near my home. Of the £25 I handed over, more than £4 will find its way into government coffers in the form of sales tax. And salvia was just one of dozens of powerful but entirely legal psychoactive substances that I could have chosen.

All that was far from my mind as the salvia took me on a consciousness-expanding journey unlike any other I have ever experienced. My body felt disconnected from "me" and objects and people appeared cartoonish, surreal and marvellous. Then, as suddenly as it had began, it was over. The visions vanished and I was back in my bedroom. I spoke to my "sitter" - the friend who was watching over me, as recommended on the packaging - but my mouth was awkward and clumsy. When I attempted to stand my coordination was off. Within a couple of minutes, however, I was fine and clear-headed, though dripping with sweat. The whole experience had lasted less than 5 minutes.

My salvia trip was part of a journey into the world of "legal highs", a new generation of powerful mind-altering substances that are growing in popularity across the world (see Table). Accurate figures are hard to come by, as these substances are rarely monitored by drug-enforcement agencies. But the proliferation of online and high-street retailers suggest they are an increasingly lucrative business, and one company specialising in legal drugs recently reported an annual turnover of $16 million.

The reasons for their rising popularity are not hard to fathom. Not only are they legal and openly available in many countries, they work. Whether or not they are a good thing, however, is more difficult to decide. Supporters argue that legal highs are a bit of fun with a social conscience - a harm-reduction measure that allows people to experiment safely with psychoactive substances while separating drug use from criminality. Others say no one should be allowed to take such powerful drugs: the risks are too great. Some of the disagreement is down to the dearth of information about the short and long-term health effects of most of these substances, their potential for abuse and their addictiveness. But legal highs are also a battleground between those who see the use of mind-altering drugs as a human right and those who think it is plain wrong.

Faced with growing use and an information vacuum, governments are playing catch-up. Some, notably the US and Australia, are clamping down on each new substance as soon as they encounter it. Some are doing nothing. Others are commissioning research into the drugs and their effects before deciding what action to take.

And this is just the beginning. With hundreds of synthetic drugs on their way, not to mention traditional herbs that are being introduced to western consumers for the first time, some believe that cheap, easily available, legal highs could render the street drugs market redundant. So what do we know - and not know - about legal drugs?

Legal highs are nothing new. Paul Anand, manager of Shiva, the shop in Greenwich, London, where I bought my salvia, has been selling them for 15 years, starting with a stall at the Glastonbury festival. "Back then, I was selling guarana, damiana and wild lettuce," he says, "basically poor imitators of cannabis." There was a small market for the stuff, but among experienced drug users they were regarded as a joke, with few discernable effects.

That all changed with the arrival of new, reliable and effective substances, beginning in the UK at least with magic mushrooms. At the end of the 1990s, vendors started taking advantage of a legal loophole that permitted the sale of fresh mushrooms as long as they were not prepared in any way. Business boomed. In the year to April 2004 the number of shops selling magic mushrooms in England and Wales rose from a handful to over 400, according to the British Crime Survey. In the same period 260,000 people bought mushrooms - an increase of 40 per cent on the previous 12 months.

In July 2005, the government closed the loophole, outlawing the sale of fresh mushrooms containing the hallucinogens psilocybin and psilocin, but by then it was too late. The demand for legal highs had been established, and high street and internet vendors rushed to fill the void with an assortment of alternatives. These include another type of magic mushroom, the fly agaric (Amanita muscaria), which does not contain psilocybin or psilocin but is packed with other hallucinogens including muscimol. Salvia is another. And then there is an astonishing assortment of psychoactive herbs, pills and potions designed to mimic the effect of pretty much every illegal drug going.
No dodgy dealers

Inside the shop, the cornucopia of offerings cannot be exaggerated. Vials and bottles crammed with herbal extracts, tinctures, seeds and powders jostle for attention with packets of "party pills". There are hallucinogens, relaxants, aphrodisiacs, trippy highs, "loved-up" pills and euphorics. All entirely legal, at least in the UK.

So why the sudden explosion? Anand says that his customers are attracted by the safety and quality of his products. "People are confident in what they're buying - that it's not cut with rat poison. They enjoy coming into the shop. They're not forced to meet a dodgy git in a UV-lit disco to buy an aspirin."

Vendors also make a selling point of legality. With drug testing increasingly routine at workplaces, 30 and 40-somethings are switching to highs that don't put them on the wrong side of the law, Anand says. And with legality comes, if not official approval, then at least an imprimatur of safety.

The majority of Anand's customers are aged between 20 and 30, he says. Most have tried street drugs and are now looking for something safer, more reliable, legal and affordable. And they're part of a growing movement: one leading vendor of legal highs, Stargate of Auckland, New Zealand, recently reported an annual turnover of NZ$24 million (approximately US$16 million).

Among the most popular legal highs are "party pills" made from compounds called piperazines, which are chemically similar to Viagra but with an amphetamine-like action. Known by various brand names such as PEP and Bliss, their main active ingredient is BZP (benzylpiperazine) - the "Z" pronounced US-style to rhyme with the "B". Originally developed as a drug to treat parasites in livestock, piperazines have been sporadically used on the dance scene for many years but began to seriously take off about three years ago - though not in the US, where they have been strictly illegal since 2002. Anand started selling them in January 2006 and says that every month they grow more popular.

The BZP story started in the late 1990s, when the drug was "discovered" by New Zealand entrepreneur Matt Bowden. The former musician and recreational drug user became hooked on illegal amphetamines in the 1990s during an epidemic of methamphetamine - "crystal meth" - addiction that swept the country. He had already lost a family member to ecstasy when, in the mid-1990s, he witnessed a friend on meth commit a horrific suicide - disembowelling himself with a samurai sword - at a party.

Bowden became determined to kick the habit. His efforts to quit led him to experiment with legal alternatives and he sought out a professor of neuropharmacology to tutor him and work alongside him on the project.

"I said, let's find something which is like methamphetamine but non-addictive and has an extremely low risk of overdose or death," Bowden says. They searched through the scientific literature and came across a piperazine which occasionally cropped up as an ecstasy alternative called A2.

"We looked at a US study and found that one part of the molecule caused liver damage in rats, but the other part appeared to be perfectly safe. That part was BZP," he says.

In 2000, Bowden used the compound to break his addiction to methamphetamine and then began giving it out for free to friends. By 2002, companies had begun making and selling BZP. The move led Bowden to set up his own company, Stargate, to market safe, legal alternatives to street drugs.

Stargate now produces and sells a range of pills based on piperazine blends. BZP is often combined with another piperazine, TFMPP (trifluorophenylmethylpiperazine), which gives the pills a relaxing, euphoric effect that has been compared to ecstasy.

Both drugs activate the 5HT serotonin receptor in the brain - the same receptor targeted by amphetamines and MDMA - and cause the release of dopamine (Neuropsychopharmacology, vol 30, p 550). This is responsible for the "high" associated with the pills, though it can also lead to anxiety, overheating and dehydration. In one survey, only half of people who had used BZP said they would describe its effects as "good"; 16 per cent said it was "good early but bad later", 10 per cent "bad" and 14 per cent "neither good nor bad". My own experience of using BZP was mixed, with some enjoyable effects but also a bout of paranoia, insomnia and a bad hangover the next day.

Worldwide, Bowden sells a million pills a year and, all told, New Zealand's legal party pills industry is worth around NZ$50 million a year. As these figures suggest, a lot of New Zealanders take BZP. In June, researchers at Massey University in Auckland released the results of a survey of more than 2000 people, commissioned by the New Zealand government. "We expected that no more than 5 per cent of those questioned would have tried BZP, but we actually found that 20 per cent of people had tried the drug, and 1 in 7 of 15 to 45-year-olds had used BZP in the past year," says study leader Chris Wilkins.

Wilkins says that the highest usage was by those in their 20s, as he had expected, but he also discovered high levels of use by people in their 30s and 40s.

A separate survey of around 1000 people carried out in Hamilton, New Zealand's seventh-largest city, yielded similar figures. It found that 12 per cent of the city's total population, and 30 per cent of 14 to 25-year-olds, had taken BZP at some point (Emergency Medicine Australasia, vol 18, p 180).

The popularity of BZP, along with anecdotal reports of adverse reactions, withdrawal symptoms and psychotic episodes, has led some politicians and doctors to start campaigning for a ban. Bowden, however, argues that his products are "harmless fun" and actually reduce demand for street drugs and the damage they cause; the pills are even labelled as "drug-harm minimisation solutions". He and other vendors have an agreement to sell them only to adults and in outlets where alcohol is not available.

"If we accept that people have the right to experiment with their minds, just as they try paragliding or drag racing, then it is the responsibility of governments to ensure that they have access to well-designed drugs," Bowden says.

There is some evidence in support of Bowden's argument that BZP reduces the demand for street drugs. In the Hamilton survey, 44 per cent of the 15 to 45-year-olds who had tried BZP said they had stopped taking illegal drugs as a result. In 2005, the head of the New Plymouth Criminal Investigation Branch, Grant Coward, said that the use of ecstasy had dropped after BZP became available. It also appears that the relatively low price of BZP diverts people away from illegal drugs. An ecstasy pill in New Zealand costs up to NZ$80; the same amount will buy you up to 12 BZP tablets. "Most users said that they would rather take ecstasy than BZP because the effect is preferable and the hangover not as bad, but they're priced out of it," Wilkins says. What is not clear, however, is whether BZP acts as a gateway to illegal drugs among people who would otherwise never have taken them.

Wilkins also points out that the drug seems to have less abuse potential than amphetamines. "It gives you quite a bad hangover, so people tend to limit their usage of it," he says. Overall, however, Wilkins says it is too early to conclude that BZP reduces harm.
Health worries

Worries are also emerging about the health effects of the drug. According to emergency doctor Paul Gee from Christchurch Hospital, BZP-related admissions were almost unheard of two years ago but are now commonplace. Between April and September 2005, his team dealt with 80 users complaining of nausea, vomiting, anxiety and palpitations. Some had seizures; two cases were life-threatening (The New Zealand Medical Journal, vol 118, p U1784). And while there have been no deaths directly attributed to BZP, in 2001 a woman died in Zurich after taking it with MDMA.

One of the biggest worries is that, because BZP is advertised as a "safer alternative", it fosters the belief that it is completely harmless and encourages people to take more than the recommended dose (about 200 milligrams). In the Hamilton survey, around a third of 14 to 25-year-olds who had taken BZP said they did not read the instructions on the packaging. Nearly half took more than the recommended number of pills, and 66 per cent drank alcohol at the same time, which is not advisable as alcohol exacerbates the dehydrating effects of BZP.

The non-addictiveness and limited abuse potential of BZP have also been called into question with a study showing that rhesus monkeys will intravenously self-administer the drug at rates as high as they would for cocaine (Drug and Alcohol Dependence, vol 77, p 161). What's more, work due to be published in the journal Neurotoxicology and Teratology shows that adolescent rats given BZP grow up into anxious adults.

With the doubts about BZP growing, it is no surprise that governments are sitting up and taking notice. In 2002 the US temporarily placed the drug on its schedule 1 rating, the same category as MDMA and heroin, and confirmed this in 2004. BZP has recently been made illegal in Japan, Denmark, Greece, Sweden and, as of 1 September, Australia. In the UK, BZP remains legal but is on the agenda for discussion at the government's advisory council on the misuse of drugs meeting on 2 November, where a decision will be taken as to whether BZP needs to be monitored further.

New Zealand, however, has taken a different and arguably more enlightened approach. In 2001 Bowden approached the government to ask for its help in regulating the new industry. In response the government introduced a new class of drug called "non-traditional designer substances", also known as class D. This class is a repository for new and little-researched drugs, such as BZP, pending further information. Class D drugs are legal, though there are some restrictions on them; in BZP's case that means a ban on sales to under-18s and in places that sell alcohol.

The government also commissioned three studies into BZP. One, the Hamilton prevalence study, has already been published. The other two concern the drug's health effects and are due out in November; Wilkins expects both to be critical. The outcome of these studies will heavily influence the legal status of BZP in New Zealand.

Whatever the fate of BZP, party pills won't be the last legal high to occupy government time. Thanks to the efforts of Bowden and like-minded individuals, new psychoactive substances - both natural and synthetic - continue to enter the market.

The next craze is likely to be for a legal high called kratom. This extract of a tree native to south-east Asia has been dubbed the "herbal speedball" for its euphoric and energising properties. Kratom's main active ingredient, mitragynine, binds to the same opiate receptor (mu) as opium, heroin and cocaine. There are no documented overdoses or fatalities and proponents claim it is non-addictive, although last year a team from Josai International University in Togane, Japan, published evidence to the contrary (Life Sciences, vol 78, p 2). It is legal almost everywhere except Thailand and Australia. In high doses it is supposed to produce hallucinogenic effects. However, when I tried it - boiling the leaves to make a nauseating tea - it merely made me sick and sleepy.

According to a US National Drug Intelligence Center report published in 2005, kratom is cheap and widely available in the US and has "high abuse potential", though up to now there have been no moves to ban it. That is sure to change. Arguably, drugs such as kratom are legal not because they have official approval but by default: they have yet to become popular enough to attract the attention of lawmakers. Once that happens - as with magic mushrooms in the UK - governments are quick to clamp down.

Another high that appears to be on the brink of losing its legal status is salvia. Also known as diviner's sage, "magic mint" or "Sally D", Salvia divinorum is a white-and-blue-flowered sage plant that grows in the Oaxaca mountains in Mexico. It has been used for centuries by the Mazatec people in shamanistic rituals and in healing.

The first westerner to experience salvia's powerful hallucinogenic effects was anthropologist Brett Blosser, now of Humboldt State University in Arcata, California. In the late 1980s, he was invited to take part in a Mazatec shamanic ceremony in which the participants rolled up salvia leaves and chewed them. The effect was profoundly psychedelic, Blosser reported.

Inspired by Blosser's account, Daniel Siebert, an independent ethnobotanist from Los Angeles, distilled the plant's juices to produce white, needle-shaped crystals which he called salvinorum A. Just a tiny crumb of this on his tongue produced what he describes as the most awesome and frightening experience of his life. "Suddenly I lost all physical awareness. I felt as though I were completely conscious and yet I had no body. I wondered if I had died," he says.

In 2002, with recreational use of salvia on the rise in the US and elsewhere, Bryan Roth, director of the National Institute of Mental Health's psychoactive drug screening programme at Case Western Reserve University in Cleveland, Ohio, took an interest. He discovered that salvinorum A is highly selective for the recently discovered kappa opioid receptor in the brain (Proceedings of the National Academy of Sciences, vol 99, p 11934). Like the other two opioid receptors (mu and delta), kappa is involved in pain sensations. But, unlike the other two, chemicals bound to it can cause hallucinations.

It's still unclear why salvia produces hallucinations. "Some of the experiences people have on salvia may be similar to the psychosis that occurs in late-stage Alzheimer's," says Roth. "There is an increase in the number of kappa receptors in the brains of people with late-stage Alzheimer's."

All studies so far have shown salvia to be non-addictive. It also appears to have limited potential for abuse. "Most people taking drugs are not looking for an out-of-body experience, they want something gentle," says Harry Shapiro from UK drugs information charity DrugScope. "Salvia is so strong that people try it once and never take it again."
Playing with fire

Even so, possession of salvia has recently been made an offence in four US states - Louisiana, Missouri, Tennessee and Delaware - and a federal ban appears inevitable. Thomas Prisinzano of the University of Iowa in Iowa City, who is studying salvia to research new methods for treating substance abuse and pain, believes it is only a matter of time. "If LSD is schedule 1, then salvia will almost certainly be classed the same," he says.

Some researchers would welcome a ban on salvia and other new drugs. One of these is pharmacologist and substance misuse researcher Fabrizio Schifano of St George's Medical School in London. He says that the main problem with psychoactive substances - and hallucinogens in particular - is that they may incite psychosis. "How do you know if someone will have a sensitivity to the drug?" he says. "I am really worried by the prevalence of these drugs, and the fact that most users get their information from the internet. It is not peer-reviewed research, just people's opinions, and that is very dangerous."

Tim Kendall, deputy director of the Royal College of Psychiatrists research unit, says: "When you take salvia you are playing with fire. People can be very damaged in terms of their personal functioning. They frequently have flashbacks that intrude into their life, which can be almost like a post-traumatic stress problem after very bad experiences."

"My recommendation is that people should keep their minds clean," adds Roth.

Others believe that knee-jerk bans are the wrong approach. People have a natural drive to enter alternative states of mind, argues Richard Boire from the Center for Cognitive Liberty and Ethics in Davis, California. "The role of governments is to prevent harm to people and society from dangerous drug use. I think the government has lost sight of this and now thinks its role is to stop people from entering other mindsets."

For governments intent on pursuing prohibition at all costs, there is a sobering thought. For every banned psychoactive substance there are dozens more that remain legal. The legendary pharmacologist Alexander Shulgin has synthesised more than 230 novel designer drugs, and according to psychologist John Halpern, associate director of alcohol and drug abuse research at Harvard University, there are dozens of legal hallucinogenic herbs besides salvia that are already widely available on the internet and growing in popularity (Life Sciences, vol 78, p 519). What is more, there is clearly a demand for the stuff, and plenty of people like Bowden willing to supply it. Salvia, BZP and kratom may be on the way out, but others will take their place.

From issue 2571 of New Scientist magazine, 29 September 2006, page 40-45

A team led by Lary Walker at Emory University in Atlanta, Georgia, took beta-amyloid from such plaques and injected it into the brains of young mice genetically engineered to develop plaques at about one year of age. After the injections, plaques formed much more quickly, appearing within a few weeks (Science, DOI: 10.1126/science.1131864).

"For the first time we show that the likely seed is beta-amyloid itself," says Walker.

From issue 2571 of New Scientist magazine, 30 September 2006, page 20

SNAKE-VENOM researcher Bryan Grieg Fry made his first discovery the hard way. During his PhD, he handled a snake whose venom was largely unknown. "As far as anyone knew, Stephen's banded snakes were not considered dangerous," Fry says. "I clearly proved this wrong as my body hit the ground seconds after the bite".

Several thousand snakes and more than 20 bites later, Fry, now deputy director of the Australian Venom Research Unit at the University of Melbourne, has gone one better. He now says the vast majority of snakes on the planet are venomous, even some commonly kept as pets.

Fry has spent the past five years exploring caves, climbing trees and scuba-diving for sea snakes, on a mission to catch and milk venom from as many snake species as possible. Along the way he has gained a reputation as a fearless snake wrangler and, more importantly, he has single-handedly rewritten the story of snake venom evolution.

Before Fry came along, the story went something like this. The first snakes evolved from lizards and were small burrowing creatures, less than 1 metre long. Around 60 to 80 million years ago they split into constrictor-style snakes and the advanced snakes, which are further divided into four families: Viperidae (vipers), Elapidae (cobras and coral snakes), Atractaspididae (stiletto snakes) and Colubridae (everything else).
A deadly ancestor

Leaving aside the colubrids, most of which were thought to have nothing more dangerous than slightly toxic saliva, venom was assumed to have evolved independently in each of the other three families, after they split off from their non-venomous ancestors. In these three there were thought to be a grand total of around 500 venomous species, all of which gained their venom by developing increasingly nasty saliva. Some scientists suspected there had been a common venomous ancestor to all snakes but no one had found any evidence to support the idea.

Fry began his venom-collecting mission in 2001. It was dangerous work. That year, Fry lost a friend and colleague to a snakebite, and frequently gets bitten himself. "It happens, but it doesn't make me nervous; it's all part of the job," he says, pointing out that he never goes anywhere without a doctor and a supply of antivenom.

Between trips around Africa, Australia and the South Pacific, Fry set to work analysing the venoms he had collected and the glands that produced them. The idea was to create a phylogeny - an evolutionary tree based on physical similarities - of different species of snakes and their lizard relatives.

Snake venom is a mixture of toxic proteins, so to find which proteins are produced by which snakes he sequenced messenger RNA from the cells that make up the venom glands. He then compared his results with an existing snake phylogeny created by Nicholas Vidal at the National Museum in Paris, France. Vidal had traced snake evolution through DNA extracted from liver tissue, so Fry was able to check that the similarities he'd found between venoms really did reflect evolutionary relationships. Finally, he compared his new evidence to the fossil record.

Fry's phylogeny, published in the journal Nature in February this year, was to overturn everything scientists thought they knew about snake venom. Similarities between the messenger RNA of venom glands of advanced snakes and venomous lizards revealed that these glands did not evolve independently in three snake families, or even in a common snake ancestor, but much earlier, in a lizard ancestor 200 million years ago. Venom evolved only once, in the common ancestor of all snakes plus some other reptiles, including the Komodo dragon, the green iguana and the Gila monster.

What's more, venom didn't evolve from ever more toxic saliva but from what Fry calls "recruitment events". Rather than tweaking proteins already expressed in their saliva, snakes recruited and altered cells from other parts of the body including the brain, eye, lung, heart, liver, muscle, ovary and testis. Over generations these proteins, usually involved in key biological processes such as blood clotting or regulating blood pressure, were mutated into more potent varieties and concentrated into catastrophic overdoses. The common ancestor had nine such toxins in its venom. Modern snakes have recruited 17 more.

The upshot of all this is that while the supposedly non-venomous colubrids were widely believed to have only mildly toxic saliva, Fry's work shows that they actually possess true venom. In fact, Fry has found snakes in pet stores whose venom glands "have enough poison in them to kill a human". The venom of the rat snake, for example, a common choice of pet, contains a neurotoxin which is as potent as the cobra equivalent. Fortunately for would-be pet owners, the rat snake has no front fangs, leaving these snakes with a rather crude venom-delivery system. Garter snakes, American racers and radiated rat snakes drip venom from their back teeth and even if you stuck your hand down a snake's throat you would never get a deadly bite. What's more, these snakes are primarily interested in smaller prey than humans, and what is lethal to a 2-gram frog may be fairly harmless to a 70-kilogram human.

According to evolutionary ecologist Martin Kreitman of the University of Chicago, Fry's findings shed a new light on the snake evolutionary tree. "It means that venom may have evolved first, and that what separates other advanced snakes from the colubrids are simply more advanced delivery systems for injecting the venom," he says.

That implies that snakes which crush their prey, such as king snakes, pythons and boas, may have lost their venom as they evolved to kill by constriction. Fry has found evidence that some snakes are now "evolving out" certain venom components, perhaps because it takes a huge amount of energy to create them. The venom of the marbled sea snake, for example, has become only 1 to 20 per cent as toxic as that of similar species since it began to feed exclusively on fish eggs, rather than fish.

"The vast majority of the colubrids are perfectly safe," says Fry, but be careful of any unusual snakes for sale from Asia, Madagascar and Latin America. Previously sold as pets, the olive sand snake has huge venom glands and big teeth, for example, and although the Egyptian cat snake only has small rear fangs, it is as toxic as a cobra - and there's no antivenom.

Caution at the pet store is not the only spin-off from Fry's work. Snakebites account for tens of thousands of deaths each year in South America, Africa, the Middle East and south-east Asia. The more venoms that are catalogued and understood, the greater the chance of the right antivenom being available at the right time.

Snake venoms are also making a positive contribution to human health as a source of new drugs. Captopril, developed from the venom of a lancehead viper, is one of the most widely used medications for high blood pressure. A promising new drug from the venom of the Gila monster, marketed as Byetta, may soon start stabilising the blood sugar of people with diabetes. Researchers at the University of South Australia, Adelaide, and elsewhere are researching the venom of a number of deadly Australian snakes which appears to stunt the growth of tumours by disrupting their blood supply.

In addition to 450 elapids, vipers and atractaspidids, there are over 2000 colubrids, accounting for over half the snake species on the planet. Fry estimates that well over 2000 species are venomous, and if he's right that's a lot of potential new molecules that could work as drugs.

The Stephen's banded snake that bit Fry early in his PhD turned out to immobilise its prey using a hormone that is almost identical to one that is used in the human body to regulate blood pressure. Fry recently patented the venom component that does this in both Stephen's banded snake and the inland taipan and hopes it will one day be used to treat patients with congestive heart failure. There may be many more potential drugs waiting in the wings.

Despite Fry's success, don't expect a mad rush of scientists to join him in the field. "It's a dangerous job," says Kreitman. "Fry is truly a modern adventurer, one of a bunch of guys who think it's great to travel to the most remote places in the world and risk death."

From issue 2571 of New Scientist magazine, 30 September 2006, page 51-53

Ever wish you could reach back in time and change the past? Maybe you'd like to take back an unfortunate voicemail message, or rephrase what you just said to your boss. Or perhaps you've even dreamed of tweaking the outcome of yesterday's lottery to make yourself the winner.
Common sense tells us that influencing the past is impossible - what's done is done, right? Even if it were possible, think of the mind-bending paradoxes it would create. While tinkering with the past, you might change the circumstances by which your parents met, derailing the key event that led to your birth.

Such are the perils of retrocausality, the idea that the present can affect the past, and the future can affect the present. Strange as it sounds, retrocausality is perfectly permissible within the known laws of nature. It has been debated for decades, mostly in the realm of philosophy and quantum physics. Trouble is, nobody has done the experiment to show it happens in the real world, so the door remains wide open for a demonstration.

It might even happen soon. Researchers are on the verge of experiments that will finally hold retrocausality's feet to the fire by attempting to send a signal to the past. What's more, they need not invoke black holes, wormholes, extra dimensions or other exotic implements of time travel. It should all be doable with the help of a state-of-the-art optics workbench and the bizarre yet familiar tricks of quantum particles. If retrocausality is confirmed - and that is a huge if - it would overturn our most cherished notions about the nature of cause and effect and how the universe works.

Dating back to Newton's laws of motion, the equations of physics are generally "time symmetric" - they work as well for processes running backwards through time as forwards. The situation got really strange in the early 20th century when Einstein devised his theory of relativity, with its four-dimensional fabric of space-time. In this model, our sense that history is unfolding is an illusion: the past, present and future all exist seamlessly in an unchanging "block" universe. "If you have the block universe view, the future and the past are not any different, so there's no reason why you can't have causes from the future just as you have causes from the past," says David Miller of the Centre for Time at the University of Sydney in Australia.

With the advent of quantum mechanics in the 1920s, the relative timing of particles and events became even less relevant. "Real temporal order in general, for quantum mechanics, is not important," says Caslav Brukner, a physicist at the University of Vienna, Austria. By the 1940s, researchers were exploring the possibility of time-reversed phenomena. Richard Feynman lent credibility to the idea by proposing that particles such as positrons, the antimatter equivalent of electrons, are simply normal particles travelling backwards in time. Feynman later expanded this idea with his mentor, John Wheeler of Princeton University. Together they worked out a theory of electrodynamics based on waves travelling forwards and backwards in time. Any proof of reverse causality, however, remained elusive.

Fast forward to 1978, when Wheeler proposed a variation on the classic double-slit experiment of quantum mechanics. Send photons through a barrier with two slits in it, and choose whether to detect the photons as waves or particles. If you put up a screen behind the slits, you will get a pattern of light and dark bands, as if each photon travels through both slits and interferes with itself, like a wave. If, on the other hand, you take a snapshot of the slits themselves, you will find each photon passes through one slit or the other: it is forced to pick a path, like a particle. But, Wheeler asked, what if you wait until just after the photon has passed the slits to make your choice? In theory, you could suddenly raise the screen to expose two cameras behind it, one trained on each slit. It would seem that you can affect where the photon went, and whether it behaved like a wave or particle, after the fact.

In 1986, Carroll Alley at the University of Maryland, College Park, found a way to test this idea using a more practical set-up: an interferometer which lets a photon take either one path or two after passing through a beam splitter. Sure enough, the photon's path depended on a choice made after the photon had to "make up its mind". Other groups have confirmed similar results, and at first blush this appears to show the present affecting the past. Most physicists, however, take the view that you can't say which path the photon took before the measurement is made. In other words, still no unambiguous evidence for retrocausality.

That's where John Cramer comes in. In the mid-1980s, working at the University of Washington, Seattle, he proposed the "transactional interpretation" of quantum mechanics, one of many attempts to relate the mathematics of quantum theory to the real world (New Scientist, 24 July 2004, p 30). It says particles interact by sending and receiving physical waves that travel forwards and backwards through time. This June, at a conference of the American Association for the Advancement of Science, Cramer proposed an experiment that can at last test for this sort of retrocausal influence. It combines the wave-particle effects of double slits with other mysterious quantum properties in an all-out effort to send signals to the past.

The experiment builds on work done in the late 1990s in Anton Zeilinger's lab, when he was at the University of Innsbruck, Austria. Researcher Birgit Dopfer found that photons that were "entangled", or linked by their properties such as momentum, showed the same wave-or-particle behaviour as one another. Using a crystal, Dopfer converted one laser beam into two so that photons in one beam were entangled with those in the other, and each pair was matched up by a circuit known as a coincidence detector. One beam passed through a double slit to a photon detector, while the other passed through a lens to a movable detector which could sense a photon in two different positions.

The movable detector is key, because in one position it effectively images the slits and measures each photon as a particle, while in the other it captures only a wave-like interference pattern. Dopfer showed that measuring a photon as a wave or a particle forced its twin in the other beam to be measured in the same way.

To use this set-up to send a signal, it needs to work without a coincidence circuit. Inspired by Raymond Jensen at Notre Dame University in Indiana, Cramer then proposed passing each beam through a double slit, not only to give the experimenter the choice of measuring photons as waves or particles, but also to help track photon pairs. The double slits should filter out most unentangled photons and either block or let pass both members of an entangled pair, at least in theory. So a photon arriving at one detector should have its twin appear at the other. As before, the way you measure one should affect the other. Jensen suggested that such a set-up might let you send a signal from one detector to another instantaneously - a highly controversial claim, since it would seem to demonstrate faster-than-light travel.

If you can do that, says Cramer, why not push it to be better-than-instantaneous, and try to make the signal arrive before it was sent? His extra twist is to run the photons you choose how to measure through several kilometres of coiled-up fibre-optic cable, thereby delaying them by microseconds (see Diagram). This delay means that the other beam will arrive at its detector before you make your choice. However, since the rules of quantum mechanics are indifferent to the timing of measurements, the state of the other beam should correspond to how you choose to measure the delayed beam. The effect of your choice can be seen, in principle, before you have even made it.

That's the idea anyway. What will the experimenters actually see? Cramer says they could control the movable detector so that it alternates between measuring wave-like and particle-like behaviour over time. They could compare that to the pattern from the beam that wasn't delayed and was recorded on a sensor from a digital camera. If this consistently shifts between an interference pattern and a smooth single-particle pattern a few microseconds before the respective choice is made on the delayed photons, that would support the concept of retrocausality. If not, it would be back to the drawing board.

Cramer says the plan is to do the instantaneous signalling experiment first, to iron out technical glitches from noise or errors in photon tracking, which would wreck the retrocausality experiment. Only after performing that would they add in the delay cables. "This experiment, if successful, would bring retrocausality into the macroscopic realm," says Cramer.

Other experts are supportive of the idea but sceptical of what it might mean. "It would be important to perform such an experiment just because of curiosity about interpretations," says Brukner. "If you accept the transactional interpretation, then this experiment would show a retrocausal influence." Cramer agrees it is speculative, but says the experiment is our best shot at seeing retrocausality in action. Because of the implications he is cautious, but still positive. "I don't see any show stopper yet," he says.

If the experiment does show evidence for retrocausation, it would open the door to some troubling paradoxes. If you could see the effects of your choice before you make it, could you then make the opposite choice and subvert the laws of nature? Some researchers have suggested retrocausality can only occur in limited circumstances in which not enough information is available for you to contradict the results of an experiment.

Another way to resolve this is to say that even if the present can influence the past, it cannot change it. The fact that your hair is shorter today has as much influence on your going to the barber yesterday as the other way around, yet you can't change that decision. "You wouldn't be able to talk about altering, but you could talk about causing or affecting," says Phil Dowe, an expert on causation at the University of Queensland in Australia. While it would mean we cannot change the past, it also implies that we cannot change the future.

If all that gives you a headache, then consider this: if retrocausality does exist, it says something profound about how the universe works. "It has the potential to solve what is one of the biggest problems in modern physics," says Huw Price, head of Sydney's Centre for Time. It goes back to quantum entanglement and "nonlocality" - one particle instantaneously affecting another, even from the other side of the galaxy. That doesn't sit well with relativity, which states that nothing can travel faster than light. Still, the latest experiments confirm that one particle can indeed instantaneously affect the other (New Scientist, 18 June 2005, p 32). Physicists argue that no information is transmitted this way: whether the spin of a particle is up or down, for instance, is random and can't be controlled, and thus relativity is not violated.

Retrocausality offers an alternative explanation. Measuring one entangled particle could send a wave backwards through time to the moment at which the pair was created. The signal would not need to move faster than light; it could simply retrace the first particle's path through space-time, arriving back at the spot where the two particles were emitted. There, the wave can interact with the second particle without violating relativity. "Retrocausation is a nice, simple, classical explanation for all this," Dowe says.

While the jury is out awaiting the results of Cramer's experiment, some researchers expect reverse causality will play an increasingly important role in our understanding of the universe. "I'm going with my gut here," says Avshalom Elitzur, a physicist and philosopher at Bar-Ilan University in Israel, "but I believe that when we finally find the theory we're all looking for, a theory that unifies quantum mechanics and relativity, it will involve retrocausality." If it also involves winning yesterday's lottery, Cramer won't be telling.



From issue 2571 of New Scientist magazine, 28 September 2006, page 36-39

"We wanted to know why, when people are already full, why people are still eating a lot," said Dr. Gene-Jack Wang of Brookhaven National Laboratory in Upton, New York.

"We were able to simulate the process that takes place when the stomach is full, and for the first time we could see the pathway from the stomach to the brain that turns 'off' the brain's desire to continue eating."

Wang and colleagues tested seven obese volunteers who had been fitted with a gastric stimulator -- a device that tricks the body into thinking the stomach is full, a state known as satiety.

They used a positron emission tomography or PET scan to see which parts of the brain activated when the stimulator was activated. They also carefully questioned their volunteers, all of whom were very obese, about why and when they overate.

"We thought the activated area (of the brain) must be in the satiety center, which we learned in medical school is supposed to be in the hypothalamus," Wang said in a telephone interview.

But they did not see activity there.

"We saw a lot of activity in all areas of the brain, especially in the hippocampus. That region is related to learning, memory and is also related to a lot of things such as sensory and motor impulse and emotional behavior," Wang said.

Writing in the Proceedings of the National Academy of Sciences, Wang and colleagues said the hippocampus was 18 percent more active when the gastric stimulator was on.

The stimulators also sent messages of satiety to brain circuits in the orbitofrontal cortex and striatum, which have been linked to craving and desire in cocaine addicts.

"This provides further evidence of the connection between the hippocampus, the emotions, and the desire to eat, and gives us new insight into the mechanisms by which obese people use food to soothe their emotions," said Wang.

The volunteers were all genuinely hungry -- they had been fasting for 16 or 17 hours when the PET scans were run. The stimulator succeeded in making them feel less hungry, Wang said.

But the surprise was in which brain circuits it used in doing so.

"It was very similar to a study on when cocaine abusers, when they think of cocaine, they have a craving for cocaine," he said.

"This new pathway should be explored in further studies to determine if there are any implications for treating or preventing obesity."

Only 40 percent knew the virus could not be passed by kissing on the mouth.

"We must not lose sight of the fact that HIV/AIDS is still one of the biggest preventable killers worldwide," said Health Commissioner Markos Kyprianou. "I am most worried about the decreasing attention for prevention."

Particular concern centers on the 10 countries that joined the EU in 2004. "More needs to be done, in particular to inform the citizens of new EU member states, where the epidemic is still strong, and which border the countries where the epidemic is on the rise," Kyprianou said.

Those tending to have the highest knowledge of the disease were urban young people, but despite their high level of awareness, the report found them taking fewer precautions compared with four years ago.

"We have to promote education, the use of sterile needles and syringes, and especially safer sex as complacency leads in particular the young to underestimate the potential risk," said Kyprianou.

The survey was conducted from Sept. 2 to Oct. 6 and Nov. 5 to Dec. 7 of 2005 with interviews of more than 24,000 EU residents ages 15 and up. The margin of error was between 1.9 and 3.1 percentage points.

Their work was based on measurements done with the help of the NASA-launched COBE satellite in 1989. They were able to observe the universe in its early stages about 380,000 years after it was born.

Ripples in the light they detected also helped demonstrate how galaxies came together over time.

"The very detailed observations that the laureates have carried out from the COBE satellite have played a major role in the development of modern cosmology into a precise science," the academy said in its citation.