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A struggle for Eden NS 26 apr 03

Iraq faces an uncertain future. But restoringthe country's great marshlands could bring hope and stabilityto its people

BRYANT FORLOW

THE talk now is of rebuilding Iraq. How to once again fuse its fractured peoples, cultures and religions into a coherent society with a stable economy. But for one very special comer of the country, a plan already exists. A small group of campaigners, backed by 20 expert scientists, has devised a way to restore the lower Mesopotamian marshlands, the largest wetland ecosystem in the Middle East, to their former glory. The marshes, which capture water and silt pouring from the mountains of Turkey and Iran, were the crucible of Westem civilisation, home to the great cities of Babylon and UT. Biblical scholars place the Garden of Eden here, and the Great Flood. Now the waters are all but gone, drained and poisoned as part of a genocidal campaign by Saddam Hussein's regime against the Marsh Arabs who had lived there for millennia.

But there is a way to get the marshes back, says the restoration team. This week it has released a report called Eden Again that details how. By breaching the dams Saddam built, opening up long-closed sluice gates, and rebuilding a delicate network of earth dykes, the water can again be made to flow and the soils retumed to their pristine state. It will be tough, the team admits, and to stand any chance of success the project must begin as soon as possible. But if it works, the trade, agriculture and flshing opportunities created by the restored marshes could become a beacon of hope for the rest of Iraq, helping to stabilise both the region and the country's wider economy. The team is headed by Azzam Alwash, an Iraqi-American engineer, and his wife Suzie, a geologist at El Camino College in Torrance, Califomia. They recruited a team of engineers, ecologists, hydrologists and soil chemists who together pored over scientific and technical papers, maps, satellite images and water and sofl survey,a describing the state of the region. Those documents, they believe, show the marshes are salvageable. Surprisingly, it is the haste with which Saddam Hussein's regime drained the marshes that win allow large swathes of soil to be recovered, says Curtis Richardson, director of the Duke University Wetland Center in Durham, North Carolina. "A system like a marsh has a memory," agrees Thomas Crisman, director of the University of Florida's Center for Wetlands in Gainesville, and adviser to the Eden Again project. Marsh soils naturally go through wet and dry seasons, and have fluctuating levels of nutrients and other chemicals. The sediments remaining in the dry soil will determine ho'w it reacts to flooding. Phragmites reeds, tamarisk and cottonwood trees in the region have seeds adapted to surviving dry seasons, and those remaining in the desiccated soil may still be viable. But the process of restoring the water wiu have to be carefully controlled. The US Army Corps of Engineers has expressed an interest in helping with the immediate task at hand - to remove ordnance and battlefield debris left over from the war between Iraq and Iran fought in the region in the 1980s.

But then the real work begins. The Eden Again team proposes to first reclaim the Hawizah marsh that straddles the border with Iran. This marsh is thought to be in the best condition, with large reed stands, trees, the greatest biodiversity, and soil that appears not to be too saline or contaminated by pesticides. The team plans to spend around 3 months confirming the state of the soil before opening sluice gates around the marsh to gradually reconnect the remaining fragmented pools of water and flood the region section by sectiola. This could be done as early as Novemb* 2003. Restoring the other wetlands, the great Central marsh, and the Hammar marsh to the south, will take longer. The first step will be to analyse soil samples for toxic contaminants and check the chemistry of the salt pans that have been identified from satellite images. The team has already taken some soil samples, but the coalition invasion this year has meant they have not yet been sent to the US for analysis. The fear is that the soil in some areas might be laden with sulphur, says Richardson. If it is, wetting it could produce sulphuric acid that would kill any remaining plants and seeds. Once the Central and Hammar soils have been checked, the Eden Again team, working with local marsh people, will identify small areas to become pilot restoration projects. Soils that have been dry for years, or found to be saline or toxic, will be decontaminated by flushing them with water from the Euphrates. Those found to be seriously poisoned will be permanently sealed off by earth dams and not reflooded for at least 3 years, says the Eden Again report. It will be a huge engineering task requiring help from the new Iraqi administration, the US government, private companies and the Marsh Arabs themselves. Designated areas such as Lake Hammar and Central marsh will be divided into holding ponds. Water will be channelled from one to another, flushing out salts and pesticides into individual pools that will be sealed off. Because the land is flat, high-capacity pumps similar to those used in open mines will be needed to shift the water.

Economic and envimnmental benefits As the water retums, so w!H the fish and shrimp for which the marshes used to be a seasonal breeding ground. The Eden Again [email protected] estimates that a revitalised flshing industry, plus rice, barley and date crops from the region, and products such as mats made from reeds, could be worth some $620 million a year to the Iraqi economy. Dates were a major export crop before the iggi Gulf war, and they could be growing again within 5 years. Rejuvenated marshes would also help stem desertification and abate flash floods, reduce the frequency and severity of sandstorms that have increased since iggi, and improve the quality of southern Iraq's rivers, estuaries and marine flsheries. But the possibility remains that with the water will comes a plague of mosquitoes, and with them an increase in malaria.

Thomas Naff, an expert in both Middle East studies and envirorunental science at the University of Pennsylvania iii Philadelphia, agrees the marshes will be integral to the health of Iraq's waterways and its post- war recovery. "You cannot provide the essential social and public health services without sufficient clean water.' But while the Hawizah marsh maybe salvageable, he says, rescuing the others may cost too much. Restoring them would mean removing a lot of canals, dams and dykes and other structures. That would be perfectly feasible, he ' says. "But a political decision has to be made whether it is worth the money. That's going to be a problem in Iraq - the cost could exceed $Ioo million.' There is also some concem that even when the marsh soils are restored, they will be less productive than they were. Turkey's dams have held back vital nutrients for years, and desiccated topsoils may have been blown away. The rich soils of the Fertile Crescent will take years to restore, wams Richardson. But Tom Dunne, a hydrologist on the Eden Again team from the University of Califomia at Santa Barbara, is more optimistic. Thick salt depgsfts in some areas may be protecting productive silt underneath, he hopes. Suzie Alwash is confident progress can be made within a year. If the US government is unwilling to foot the bffl, say as part of a "Marshall Plan" for Iraq, the project's advocates may approach oil companies which have an eye on reserves beneath the marshes. Another problem will be convincing Turkey to open its dams to allow more of the Euphrates and Tigris waters to reach Iraq. Saddam's policy of desertification meant that he had no interest in such a deal UN Environment Prog opes to help negotiate one. If the Eden Again project is to succeed, it will have to be taken over by Iraqis themselves. In the meantime, Azzam Alwash believes it will help rebuild trust between the West and the many people who fled the region after the abortive uprising against Saddam in 1991. "Restoration of the-marshes is a great symbol, bringing back to Iffe, from the dust and salt of the current destruction, the symbol of the start of Western civilisation," he says. "I can hardly think of anything more symbolic to the rebirth of Iraq.

Virgin birth method could found stem-cell dynasties

THE phenomenon that leads to "virgin births" in some species looks like a promising source of embryonic stem cells. Researchers are on the brink of obtaining human stem cells this way for the first time, and animal experiments suggest such cells are indistinguishable from normal stem cells. In parthenogenesis, an unfertilised egg keeps two sets of chromosomes and begins developing as if it had been fertilised. Some insects and reptiles can reproduce this way but even though an electric or chemical stimulus can induce parthenogenesis in mammals, the resulting embryos die after a few days. And that, according to its proponents, is the beauty of the technique as far as stem cells are concemed: ifproduces embryos that could never become human beings. So destroying these embryos to obtain stem cells would avoid the ethical concerns that have led to restrictions or bans on embryonic stem cell research in many countries. However, while the technique works in mice and monkeys (New Scientist, 26 October 2001, P 14), attempts with human eggs have not got far. Until now, that is. A team led by fertility specialist David Wininger at biotech firm Stemron of Maryland has grown parthenogenetic human embryos to the blastocyst stage, at which stem cells can be obtained. Cells taken from one of the embryos survived for a few days (Stem Cells, VOI 21, P 152). "It's the first time I know of parthenogenetic cells in humans," says Kent Vrana of Wake Forest University School of Medicine in North Carolina, whose team pioneered the work in monkeys. The next step is to get the cells to grow in culture indefinitely:

that is, to obtain a stem cell line. In monkeys, such a cell line has been growing for over two years, and it makes the human experiments all the more relevant. According to Vrana, extensive analysis of the monkey cells suggests that they are indistinguishable from normal embryonic stem cells. "They are identical to ESCs by every known criterion we have tested," he says, adding that details will soon be published in a peer-reviewed journal. A lot of work still has to be done to ensure any tissues made from parthenogenetic stem cells are absolutely normal, says Jerry Hall of the Institute for Reproductive Medicine and Genetics in Los Angeles. But he is optimistic. "Patients are so interested in this procedure, and we are confident enough in its feasibility, that we have been willing to store eggs for use as soon as safety and effectiveness is shown," he says. Since eggs are needed to make parthenogenetic stem cells, one potential problem is that the technique could not be used to make matching stem cells for men or for women after menopause. Therapeutic cloning, by contrast, could provide matching stem cells for any individual. However, because cells made by parthenogenesis have two identical sets of chromosomes, rather than one set each from the father and the mother, they have less variation in the surface proteins on cells that can trigger immune reactions. Wininger thinks it will possible to establish a bank of parthenogenetic stem cells that could provide cells to suit most individuals. And such banks would be much cheaper than creating stem cells from scratch for each individual. Sylvia Pag6n Westphal, Boston

Ibogaine

BY the time Sheldon Pelletier tumed 12 he thought he had only a few weeks to live. A heroin addict for the past six years, living on the streets of Vancouver, he had lost cbunt of the number of times he'd tried to kick the habit and failed. "Usually, Id make it to day four," he recalls. "on the fourth day, you get through most of the physical pain and then your brain clears up. That's the worst, because you have to deal with your life.'

Then he heard about a mysterious drug that could help people like him. Called ibogaine, it wasn't available from doctors, but an underground clinic in Vancouver was offering it to those in need. Pelletier eventually took three doses of the capsules. The second time, they triggered a bout of intense hallucinations. He saw scene after scene from his past experiences - both pleasant and unpleasant ones. When he came round, Pelletier had lost all desire for a fix of heroin. That was last September, and he's been off heroin ever since. Ibogaine, the substance that has made such a difference in Pelletier's life, is an unlikely panacea. Its advocates claim it is a folk remedy unsurpassed for kicking heroin. A few even suggest it is a universal cure for drug addiction. But the evidence is scarce. There have been no controlled clinical trials, and there have been troubling side effects, including heart problems and even a few deaths. Partly for this reason, the few scientists working on ibogaine are trying to make safer derivatives. Two such products are nearing human tests, and their developers hope to find out in the next year or two if their long struggles will finally bear fruit. Ibogaine is an alkaloid compound that comes from the root of a shrub, Tabernanthe iboga, which grows in Gabon, West Africa. Here followers of the Bwiti religion use it in ceremonies for its vision-giving properties. In the early ig6os, a young New York student named Howard Lotsof heard of ibogaine while he and his friends - several of them heroin addicts - were experimenting with a wide range of drugs. After trying it, five of the seven addicts found to their surprise they had lost their heroin cravings and stopped taking heroin for up to six months. Ibogaine's potency was so striking that Lotsof eventually decided to make championing the compound his life's work. As the years passed, more and more people found that even a single dose of ibogaine could eliminate the horrors of heroin withdrawal and keep them off drugs for months at a time, even permanently. It seemed equally effective in helping people kick cocaine, and a few addicts found they could also quit smoking or drinking. "I realised the most important thing could do was bring ibogaine to the medical community," says Lotsof, who now heads the Dora Weiner Foundation, a non-profit drug users'advocacy group in New York City. We certainly need something new to help heroin addicts. The standard options are psychotherapy and regular prescriptions of an alternative opioid - usually methadone - that staves off withdrawal symptoms but gives no high. The theory is that addicts are stabilised on methadone before gradually cutting their dose, but many end up hooked on methadone instead, sometimes taking heroin too. A new option in some countries is a drug called buprenorphine, but again, this merely replaces heroin with another, more manageable opioid. Cocaine addicts have an even bleaker outlook than heroin users, with psychotherapy their main recourse. Part of ibogaine's appeal is the possibility that addicts will be drug-free after only one or a few doses, or at worst may need only periodic doses, perhaps once a month. But you couldn't call Lotsof's campaign a success. In the US ibogaine is a Schedule I drug just like heroin, which means that its use is illegal except for approved research. Belgium and Switzerland impose similar restrictions. Most other countries, including Britain, don't ban ibogaine outright, but neither do they sanction its medical use, so it remains an underground treatment almost everywhere. Ibogaine researchers say it deserves better. "There's an old adage in medicine: listen to your patients," says Stanley Glick, a neuro- pharmacologist at Albany Medical Center, New York. "If you hear the same anecdote from enough people, you've got to believe there's something worth investigating." Glick has led some of the most persuasive studies of ibogaine's effects in animals. He and others have found it binds to a bewildering range of receptors in the brain's nerve endings, interfering to some degree with many of the brain's signalling systems. These include the opioid receptors that also bind morphine, the substance to which heroin is converted in the brain and that is responsible for its effects. Ibogaine also binds to receptors for glutamate and acetylcholine, two of the brain's key signalling molecules.

It is still a mystery which and how many of these actions account for ibogaine's effects. But it clearly works. Glick showed that if rats addicted to cocaine or morphine were dosed with ibogaine, their appetite for the drug dropped off sharply and remained low for several days to weeks. The animals also showed few signs of withdrawal. Still, as every researcher knows, what works in rats may fail in humans. Deborah Mash, a neuropharmacologist at the University of Miami Medical Center has done more research than anyone else with human subjects. In 1993, the US Food and Drug Administration gave Mash permission to start human studies. But unable to get funding for the trials, she headed offshore to the Caribbean island of St Kitts in 1996. There she could raise money by charging patients, which is not usually allowed for experimental drug treatment in the US. Her clinic has now given ibogaine to more than 280 patients, most of them heroin addicts. "It's very effective - well above standard treatment," says Mash. But she refuses to give figures, saying that they would be meaningless based on so few patients. Ibogaine also seems to cut drug cravings in her patients who are cocaine addicts, she says. Critics point out that Mash's patients are hardly typical addicts. "Right away, you're starting with a biased sample - people who can afford that kind of intervention, or come from families that can," says Herbert Kleber, director of Columbia University's division on substance abuseinNewYorkCity. Still, Mash is convinced by what she sees. "I've got people who haven't been able to put together 3o days [of abstinence], and then they get ibogaine and they can string together six months," she says. "Is that a treatment success? You bet it is." Some are still drug-free more than six years later. Mash stresses, however, that ibogaine alone isn't the answer; addicts still need psychotherapy. "You get people suffering from years of substance abuse," she says. "They don't have jobs, they've lost their friends - you've got to rebuild this person, and a single dose of ibogaine is not going to do that." Aside from Mash's research, the literature on ibogaine's use in humans comprises a motley collection of case studies. When Lotsof surveyed this research in i995 he found that in 10 Of 52 treatments patients stayed off drugs for a year or more, although they kicked their habit within two months. evidence is ambiguous, says Frat octtal director of the treatment research and development division at the US National Institute on Drug Abuse (NIDA) in Bethesda, Maryland. "There are some interesting, striking stories of people actually stopping drugs," he says. "However, there are other stories of people who did not stop, and there are stories of people who got serious injuries and died while taking ibogaine." Because those deaths occurred in informal treatment settings rather than in carefully monitored medical trials, no one knows for sure whether ibogaine or some underlying medical condition was the cause. But ibogaine is known to have several worrying side effects, such as slowing the heart rate and possibly causing nerve damage at high doses. To complicate matters further, people metabolise ibogaine at remarkably different rates so it's hard to predict the effect of any given dose. "Ibogaine itself is probably never going to be used," says Kleber. "It's too toxic He is not the only one who thinks this. In i995, the NIDA convened a panel of experts, many from the drug industry, to consider further investigating ibogaine. After hearing the evidence, the panel voted 9 tO 4 against going on. Vocci says: "They figured it wasn't worth it. It was going to be a problematic drug.' That means the real action in scientific circles has shifted away from ibogaine itself towards two close molecular cousins. The hope is that these will offer the same benefits as ibo gaine but with fewer side effects. And the patents on these drugs have much longer to run - a big plus for drug companies unwilling to ine itself, as the first of Lo to expire this year. Is side effects, Glick joined forces with medicinal chemist Martin Kuehne at the University of Vermont to find a less toxic alternative. After testing about 15 substances, they came across 18-methoxycoronaridine (i8-MC), a synthetic relative of ibogaine that differs at just three points in the complex, multi-ringed molecule. When given to rats addicted to cocaine or morphine, this compound was as effective as ibogaine at reducing the amount of drugs they self-administered and it appeared to have fewer side effects. It also eliminated morphine withdrawal symptoms. Interestingly, 18-MC was even more effective at reducing rats' craving for nicotine, Glick found.

Universal cure In the brain i8-MC binds to some of the same receptors as ibogaine. The one to which it binds most avidly is the relatively rare alpha-3-beta-4 nicotinic receptor. This receotor is characteristic of a circuit called the altemate reward pathway, which may modulate the brain's main dopamine reward pathway. Glick thinks that 18-MC may dampen down drug cravings via this route. "We've rediscovered the importance of this other pathway, and it serves to regulate the primary reward pathway," he says. If he's right, the implications would be huge. Glick would have a drug that could muzzle any addiction: heroin, cocaine, alcohol, nicotine, you name it.

But as sceptics are quick to point out, that notion is a long way from being proved. "I've been in this field 40 years and come across a lot of 'universal cures, and haven't found that any of them stand up," says Kleber. Addiction is a many-faceted disorder, he says, with genetic components and social ones, and there can be no one cure. Not everyone agrees that humans even have an altemate reward pathway. Because of its association with ibogaine, Glick has struggled to get funding for i8-MC's development. "Ibogaine has achieved a degree of notoriety," he says. "Guilt by association has been a constant thom." In November, however, a group of investors - whose identity he prefers to keep secret - agreed to raise $5 million in the next two years for 18-MC's first clinical trial. I Glick faces some competition. Mash is working on her own compound, a natural metabolite of ibogaine called noribogaine, which she thinks is the true source of i bogaine's anti-addictive power. Within hours of taking ibogaine, the body has converted most of it into noribogaine. Mash has found that, as with ibogaine, giving noribogaine to addicted rodents stops them helping themselves to morphine or cocaine and stops withdrawal symptoms. Noribogaine also binds to many different receptors in the brain. Mash thinks the most important of these is the mu- opioid receptor, the main binding site for morphine. Morphine flits repeatedly on and off this receptor, and that may account for its kick. Mash thinks noribogaine locks firmly onto the receptor and stifles the stimulus. Mash has not yet given noribogaine to humans, but for several years she has been checking its levels in her St Kitts patients after they take ibogaine. Noribogaine levels peak a few hours after taking ibogaine, just as the hallucinations and heart effects start fading. And one patient who quickly converted ibogaine to noribogaine had no hallucinations. In contrast, a slow metaboliser had hallucinations for hours. The implication is that using noribogaine may get round some of ibogaine's side effects. Within the next six months Mash should be ready to seek FDA approval to test noribogaine in US patients. But she worries that in shedding ibogaine's hallucinogenic baggage she may also lose one of the keys to its success. Many patients say the hallucinations allow them to review their lives and past decisions, and that they emerge from the experience resolved to do better. "For some, it really is somewhat of a life-transforming experience," says Mash. Certainly, that was true for former addict Pelletier, who thinks the visions forced him to deal with the reasons he started taking drugs in the first place, and let him do so without the fear that would usually accompany starting over in life. He recalls: "It really cleansed me out - the hallucinations, the visions are mandatory if you're trying for something more than physical detox." But until someone tests noribogaine in humans, no one will know whether it has the same effect as ibogaine without the hallucinations. If they don't, Mash thinks ibogaine's Schedule I status should be revoked so that doctors could provide "compassionate use" of it on an unlicensed basis. She says: "They're going to take it once or twice in their life. Then let them have noribogaine. That's going to keep the cravings away, and keep the depression away. And that's something a pharmaceutical company can make money on.' For all their tantalising promise, though, ibogaine and its derivatives remain the poor relations in the drug-treatment world. "Ibogaine was an outsider's invention," says Lotsof. "It was a drug principally discovered and developed by drug ugers. If you were a researcher who had spent years developing your career, the last thing you'd want is that someon6 with no academic credentials has developed the grail that you've been seeking.' Mash agrees one of the main obstacles is ibogaine's image problem. "It's got every dam thing going against it," she says. "But meanwhile it's helping people, and that's why it's never gone off the radar screen.'