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NS 20 oct 2001

Career guidance Now we can persuade cell implants to grow into the right tissues

ADDING tiny particles that release the appropriate chemical signals could help cell implants repair or replace damaged tissue. The technique has already helped fetal brain cells survive and thrive. "It's a significant advance in tissue engineering," says Robert Langer, a tissue engineer at the Massachusetts Institute of Technology in Cambridge. Getting the right biochemical environment around implanted cells is vital. Without it, they will die or develop into the wrong kind of cell. For instance, nerve growth factor (NGF) has to be supplied to the experimental cell transplants intended to treat spinal cord injuries, Parkinson's and Huntington's diseases. But taking NGF as a drug can cause extreme side effects such as burning sensations. To avoid this, researchers have tried injecting NGF directly into the brain. "The problem is that it doesn't last for very long," says biochemist Mark Saltzman of Cornell University in Ithaca, New York. Instead, Saltzman's team made microscopic particles containing NGF from the slow-dissolving material used for surgical sutures and mixed them with fetal brain cells containing cholinergic neurons. When the researchers implanted this mix into the brains of healthy adult rats, they found that levels of NGF around the implant peaked after seven days and dropped back to normal levels by three weeks. Higher levels of a brain enzyme called choline acetyltransferase suggested that the implanted cholinergic neurons were thriving. "It's pretty convincing evidence that indeed it was working,' says Jeffrey Kocsis, a neurobiologist at Yale University.

Langer agrees. "It's the first time that cells, synthetic elements and controlled release have been combined and programmed to aid cell transplantation," he says. "This approach could be used to affect any type of cell or tissue." The microparticles could also be tailored to deliver any protein or drug, says Saltzman. And if coated with molecules that attract particular cells, the drug could be delivered only to those cells. Ann Ananthaswamy More at: Nature Biotechnology ivol i9, p 934)

Ozone unfriendly A quartet of "green" chemicals now face a total ban

FOUR chemicals being marketed as harmless to the ozone layer may be nothing of the sort, new research suggests. As evidence grows that the ozone hole over the Antarctic is not healing as expected, an international coalition of governments will discuss this week whether to ban them. Top of the list is n-propyl bromide, a new solvent approved in 1997 by the US Environmental Protection Agency as an acceptable substitute for ozone-depleting substances such as CFCS. The chemical was known to be a potential ozone-eater, but it survives in the environment for less than a fortnight, so regulators assumed it could not reach the ozone layer.

But Donald Wuebbles of the University of Illinois, Urbana-Champaign, and others have since warned that when the substance is released in the tropics, the dynamic weather systems there can launch it into the stratosphere within days. Even if the chemical breaks down in the lower atmosphere, they say, it could still be churning out by-products that react with ozone-depleting bromine and help transfer it into the stratosphere. The Montreal Protocol limits emissions of ozone-destroying chemicals. This week, a scientific panel will tell a meeting of signatories in Colombo, Sri Lanka, that n-propyl bromide's potential for depleting ozone is 30 times more in the tropics than at northem latitudes. But some countries are questioning the research and may oppose a ban. China, for example, says it doesn't believe that n-propyl bromide depletes ozone. UN scientists estimate that up to 10,000 tonnes of the chemical, often marketed as "environmentally friendly', are made each year. That could rise to 50,000 tonnes a year by 2010, they say. Three other chemicals may also be banned this week. Hexachlorobutadiene is a solvent and by-product of the manufacture of PVC. Tens of thousands of tonnes are made each year. Halon-1202 is an older chemical still used to fight fires in military aircraft and tanks, and 6-bromo-2-methoxy-naphthalene is used in the manufacture of the agticultural fumigant methyl bromide. There are growing fears that there could be many other as-yet unidentified ozonedestroying chemicals in widespread use. 'Relatively small amounts of these new substances are being produced, but the levels of some of them are growing rapidly in the atmosphere," says John Pyle of the Centre for Atmospheric Science at the University of Cambridge.

'We cannot be complacent. If enough of these new chemicals are manufactured, we will delay the recovery of the ozone layer quite significantly,' wams Mario Molina of the Massachusetts Institute of Technology, who won the chemistry Nobel Prize in 1995 for his work on the thinning ozone layer.

Predictions that the Antarctic ozone hole would begin to heal in the late 1990s have been proved wrong. Last week the British Antarctic Survey reported that this year's hole covered 24 million square kilometres, more than twice the size of Europe. This equals the hole that opened up in 1999-only the holes in 1998 and 2000 have been bigger. Fred Pearce

NS 1 sep 2001

Many happy returns Fancy chalking up a century. You might just have it in you

THE secret to a long life may be within our grasp. We are close to pinpointing the genes that determine how fast we age-a discovery that would open the door to developing drugs that slow the ageing process. Only a few people live to 100 or more, and anecdotal evidence suggests that the trait fof longevity runs in families. But no one knows if specific genes predispose people to live to extreme old age. To find out, Annibale Puca of the Howard Hughes Medical Institute in Boston recruited 137 sets of siblings where one was at least 98 years old and had a brother aged at least 91, or a sister aged at least 95.

Puca and his team carried out a type of genetic study called "linkage analysis", which reveals how likely it is that a region of the genome is associated with a particular trait. The researchers found a region on chromosome 4 associated with long life. The team is 95 per cent certain that it has identified the correct group of genes, Puca says.

"It's a technical tour de force," says Tom Johnson at the University of Colorado, Boulder. "No one has been able to do this in humans [before]."

Once we know what these genes code for, it may be possible to develop drug therapies that mimic their effects, says Huber Warner, associate director of the biology-of-ageing programme at the US National Institute on Ageing in Maryland. "It could provide a biochemical way to manipulate health and lifespan." .

Puca and his team think that variations in one or more genes in the region affect the rate of ageing. Scientists have already found that centenarians have a lower frequency of the ApoE gene, which is associated with Alzheimer's disease. But "these are not longevity genes," says Puca. 'This gene is associated with one of the major diseases of ageing. We expect that centenarians have fewer of these genes, since they have fewer typical diseases of ageing.' What's more, previous studies have been done by looking at the effect on ageing of known genes suspected of playing a role. Puca's study, in contrast, is the first to pick out from the entire genome the most important gene or genes linked to longevity. 'it could be a 'slow ageing' gene," he suggests. 'I'm surprised to find a single gene region with this much effect,' says Warner. "It must be a really basic process that affects a lot of different basic systems-some universal, general process." James Carey of the University of California, Davis, agrees. He says that Puca's study is important because it points to a particular region of a particular chromosome that appears to have a strong bearing on the rate of ageing. "The next steps must involve independent verification, then narrowing down to a small subset of genes if possible, and, most importantly, identifying the mechanism," he adds. Whether this will enable us to develop ways of slowing ageing depends on what we find, Puca says. 'Some genes and pathways are harder tcrmodify than others." His team hopes to isolate the gene or genes within six months. Sibylle Hechtel

More at: Proceedings of the National Academy of Sciences (voi 98, p 10,505)

Naturally toxic
Ginkgo biloba may be "natural" but is it safe during pregnancy.?

A COMMONLY used herbal supplement could be causing birth defects, say researchers who have discovered high levels of the toxin colchicine in one brand of a supplement often used by pregnant women. During routine tests of placental blood taken from 24 pregnant women, Howard Petty and his colleagues at Wayne State University, Detroit, were surprised to find colchicine in five of them. The levels were high enough fo have harmful effects and were "entirely unanticipated', they say.

Colchicine is found naturally in many plants. It is sometimes used to treat gout, but it interferes with cell division and can be fatal at high doses. At lower levels, it is known to damage fetuses. Petty and his team were puzzled where the colchicine in the blood samples had come from, until they realised that the women with the chemical in their blood had all been taking herbal supplements.

When the researchers tested a popular herbal supplement containing ginkgo biloba bought at a local pharmacy they found that it contained colchicine. Ginkgo biloba, extracted from the maidenhair tree, is normally used to treat Alzheimer's and memory loss in older people. But it has recently become popular among young people who hope it will enhance memory.

The researchers only tested one sample of ginkgo biloba, although they haven't said which brand. 'It would be premature to generalise this to all manufacturers," says Petty. But he wams that the problem could apply to other herbal medicines. 'Such supplements should be avoided by women who are pregnant or trying to conceive," the researchers report in a future issue of Chemical Research in Toxicology. 'It should never be assumed that because a therapy is 'traditional' or 'natural' it must be safe,' adds a spokeswoman for Britain's Royal College of Midwives. Many herbal medicines are unregulated,. so it's impossible for consumers to tell if they contain harmful chemicals. They tend to contain 'a whole package of active ingredients', says John Henry, a toxicologist at St Mary's Hospital in London. liga Nielsen

Rice Patenting victory for India

INDIA has scored a signiflcant victory in its long-running battle with a US company over a patent on strains of basmati rice. The US Patent and Trademark Office (USPTO) has weakened the controversial patent it granted In 1997 to Texas-based RiceTec for three strains of "basmati", a rice traditionally grown In the Himalayan foothills of India and Pakistan.

RiceTec claimed that the strains were different from traditional basmati in 20 ways, such as grain size, starch content and yield. In April last year, India's Agricultural and Processed Food Exports Authority challenged three of RiceTec's claims, arguing that genuine basmati could display the same qualities. lt also claimed that only rice-grown in the Himalayan foothills could be termed "basmati'. "We waged a focused battle. The three claims challenged were sufficient to knock out RiceTec's claims on basmati,' says Raghunath Mashelkar, head of India's Council of Scientific and Industrial Research, which collected evidence for the case.

The USPITO's new ruling reduced RiceTec's claims from 20 to 5. lt also said that RiceTec could not market the rice as basmati. India is now developing a digital 'library" of Its traditional knowledge, which US and European patent offices will have access to. Padma Tata