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NS 2 sep 2000

New rules let researchers in the US join the race to harness stem cells

AFTER months of soul-searching, the US National Institutes of Health has set out guidelines that will allow researchers to apply for public funds to work with stem cells derived from human embryos. Publicly funded researchers will at last be able to join those in industry who are developing ways to grow new tissue and organs for transplant, from patients' own tissue or from "off-the-shelf" tissue banks. Embryonic stem cells are a type of primordial cell that can be coaxed to grow into any other type of cell. Many oppose their use because they must initially be harvested from an embryo, which is inevitably destroyed in the process. Proposals for legal changes isssued in Britain last month go further than the new American rules, as they would allow researchers to extract stem cells from embryos (New Scientist, 19 August, p 4). "There will be some experiments that people have in mind that they can't do that they could do in Britain," says Paul Berg of Stanford University in California. In the US, researchers will not be allowed to work with human stem cells generated by cloning, which involves taking genetic material from an adult cell and putting it in a fertilised egg. Also, public funds will not support harvesting stem cells from embryos, so researchers will have to buy them from private labs. "I happen to think that this is wrong. I think we should be funding the establishment of embryonic stem cell lines," says John Gearhart of Johns Hopkins University in Baltimore. Gearhart, who plans to apply for public funding, led one of two private groups that in 1998 managed to isolate and grow human embryonic stem cells.

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Despite the limitations of the new guidelines, numerous scientific organisations welcome them as they are expected to open up the field to more research and greater public oversight. 'The most significant consequence is that the work is going to move forward rapidly," says Gearhart. He predicts that in as little as three years, therapies based on embryonic stem cells may be beginning c@ical trials for conditions such as spinal cord injuries. The guidelines have to conform to a law that prohibits government funding of research that destroys embryos. But antiabortion activists, and even some prochoice groups, say they run counter to the spirit of the law. "Even the President's own bioethics advisory board has said that it's disingenuous," says David Prentice of Indiana State University. He points out that stem cells taken from adults retain many of the properties of embryonic stem cells and studying them raises no ethical issues. When Congress reconvenes next month, the Senate is expected to vote on a bill allowing public funding to harvest stem cells. But senators who oppose stem cell research are expected to sponsor competing bills to scupper the change. Nell Boyce, Washington DC

It's in the air We may be able to pick up chemical signals after all

THE debate over whether pheromones influence our behaviour has been fired up by the discovery of what may be a working gene for a pheromone receptor. While pheromones are common in insects and lower mammals, which use them for everything from attracting mates to marking trails, whether such chemical signals affect humans has long been contentious. Now Peter Mombaerts of Rockefeller University in New York and his colleagues have found eight DNA sequences in humans that are similar to genes for mouse or rat pheromone receptors. The prevailing theory is that any pheromone receptor genes in humans will be defective relics of a time when our distant forebears used pheromones. Indeed, seven of the genes the researchers came across were flawed. But an eighth gene, VlRL1, has no such defects and could produce a protein similar to a rodent pheromone receptor. "We believe it's a counterpart," says Mombaerts. "It has several of the hallmarks." When the researchers examined a wide variety of human tissues and organs, they found VI RL1 messenger RNA in the lining of the nasal cavity, which strongly suggests that the protein is made there. And when they looked at 11 individuals from different ethnic backgrounds, they found they all had the gene. They are now trying to clinch their theory by proving that the protein is present in neurons. "It's a pivotal paper," says Charles Wysocki of the Monell Chemical Senses Center in Philadelphia. "It opens some fantastic doors." But a few essential questions still need answering, he says. For example, are the rodent receptors on which Mombaerts' team based its search restricted to the vomeronasal organ (VNO) that detects pheromones? If not, the rodent receptors-and by implication the human one-might do something other than detect pheromones. Exactly how we might detect pheromones is still open to question. While humans seem to have a similar structure to rodents' VNO early in life, there's no evidence that it's functional (New Scientist, 25 January 1997, p 36). However, like rabbits and pigs, people might detect pheromones through the main olfactory system. Even if people do turn out to have a pheromone receptor, don't go rushing out to buy the perfumes that supposedly contain sex pheromones. While Martha McClintock of the University of Chicago showed in 1998 that menstruation can be synchronised by pheromones, there's little other evidence of pheromonal communication between people. And even Mombaerts believes there are few active pheromone receptor genes in humans. "This could very well be the only one,' he says. Alison Motiuk

Source: Nature Genetics (vol 26, p 18)

Stefano Padulosi head of underutilized food crops for the International Plant Genetic Resources Inistiute (IPGRI) Rome

You brought rocket to the vegetable markets of Europe. How did it happen, and why? Rocket has been picked as an aphrodisiac plant since Roman times. Virgil praised it. In the Middle Ages it was forbidden in monasteries because of its ability to excite sexual desire. If you go walking in Italy today-for instance in Pompeii, the town where I live-you will see a lot of it. In the 19th century the British took it to India, where it is grown for seeds to make an oil which has pesticide properties. But in the Mediterranean it has always been a spicy vegetable. Till the early 1990s it had never been properly cultivated, and very little science had been done on it. It was mostly harvested from the wild and was getting rare. We began to realise that it was quite an important vegetable crop for many people. So we established a network for cultivation through our Underutilised Mediterranean Species programme. For the first time we cultivated Diplotaxis muralis and tenuifolia, the most spicy rocket species. A lot is now grown in Veneto in northern Italy. And it is now available all over Europe. The Germans especially like it.

Many people randomly pick plants from the wild and sell them. How much of a threat is this to the species' survival? Medicinal plants and herbs especially are a big issue now. For instance, in Crete they have an indigenous variety of oregano, Oreganum dictamnus, that has almost disappeared because of harvesting. lt is difficult to get data on such practices, but there is a large hidden market. International companies go to local people-in the Balkans and Turkey, for instance-and ask them to collect the plants. As a result the plants are disappearing before we know much about them. Something must be done.

You mentioned oregano. I buy pots of dried oregano at my supermarket. Is that taken from the wild? Probably. Most of it comes from the wild. Morocco is the biggest source, then Turkey, where collection is the most aggressive and organised. Nobody has ever surveyed how it is being harvested. I wouldn't say it is becoming endangered yet. But in ten years it could be in such short supply that people no longer get an income from it.

So why has science ignored these minor crops? The green revolution encouraged scientists to concentrate on a handful of major crops. Remember, half our energy requirements now come from a few

varieties of maize, rice and wheat, and 95 per cent comes from just 30 crops. But as a result, minor crops are badly under-represented in gene banks. I did a study for IPGRI [international Plant Genetic Resources Institute] in 1998 and found that 78 per cent of the accessions in seed banks are of a handful of major crop species. Of the other 5300 species, 80 per cent of them are represented by less than 10 accessions each. And more than half have just one accession. Many species are not surveyed or collected at all. We have to stop neglecting these species in our research. To do that we need partnerships with farmers, who know about the crops, and networking between countries to collect that knowledge.

But aren't these minor crops just a sideshow in the drive to feed the world? Globalisation has been bad for minor crops. Many of them have been replaced in fields by 'improved' varieties of the major crops. But the amazing thing is how many there are. We know of 1000 edible food crops in India and 1100 in North America. Ghana has 2500. Underutilised crops are often highly adapted to local niches, especially marginal areas. While they are ignored by scientists and poorly represented in seed banks, they may be well known to locals, who have detailed indigenous knowledge. They can be vital for the food security of poor rural communities. The green revolution encouraged us to think about food security in terms of the quantity of food. But there is a growing interest in analysing the quality of food. Some green revolution crops are poor in vital nutrients such as calcium, iron, and vitamins C and A, but often underutilised crops are rich in these nutrients. One study found four African homegarden crops, leafy vegetables with twice the micronutrients of spinach.

Yet despite all this potential, why is the collection of underutilised crops shutting down? In the past there used to be a lot of collaboration between Northern and Southern countries. I once worked at the International Institute of Tropical Agriculture in Nigeria, largely because it got a grant from Italy. People were coming from Italy and elsewhere in the North to support collecting plants from the wild as well asfrom African fields and were replicating material to take home. But today there is much less collecting for international research. Cash is short; there is a new emphasis on knowing what you have already in gene banks. At the same time, the UN Convention on Biological Diversity, signed at the Earth Summit in 1992, has opened the eyes of many Southern governments to the economic value of their biodiversity. Countries are closing their borders to prospectors because of fears about biopiracy. The Millennium Seed Bank, being built at Kew in London, which will be collecting arid species based on bilateral deals mainly between Britain, Egypt and Jordan, is a rare example of a new collecting initiative.

Your current job is looking for underutilised crops in Central Asia. Yes. I will be going to Turkmenistan in October, working on the pomegranate. Turkmenistan has the largest collection of pomegranate fruit trees in the world, with 1117 accessions that have never been catalogued. lt is at the Garigala Experimental Station, near the capital Ashgabat.

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What's special about Central Asia?

lt is the centre of biodiversity for the wild relatives of most of the world's fruit trees. At Garigala, there are a great number of fruit species; we don't know quite how many yet. We are also collecting and surveying in the wild. We are visiting a national forest reserve where the pomegranate grows wild. The wild apple and apricot forests of Kazakhstan and the walnut forests of Kyrgyzstan have huge genetic diversity. Over the coming months we will be collecting wild pistachio. This is an interesting case. Although central Asia is the home of this species, these countries have never paid attention to it until now. Yet in neighbouring Iran and Syria, where I am now based, they are the biggest producers of pistachio nuts in the world.

What else are you working on in Central Asia? Central Asia is also a great place for water melons and we are currently cataloguing them, too. The most fantastic discovery was a farm in eastern Uzbekistan. The farmer used to work for the state, visiting farms and giving them advice. While travelling, he came across so many types of water melon and started building a collection. He planted them, out in a small plot on the collective farm where he lived, and propagated the material. But eventually he lost access to the land, so he collected samples of everything. He put the seeds in packets and the packets into bags-everything numbered and with dates of their propagation. And that is what we found during our survey. He is very old now. But he showed us everything; his life's work. We have mobilised local scientists to assess his material so that we can put names to these varieties, and we are trying to arrange a network of farmers to plant out the accessions again. Scientists usually think of farmers as collecting seeds in a clumsy way. In reality there do exist farmers like this one, who are much more meticulous and scientific in their approach.

Which crops and species should got priority as the food of the future? Priority is a word used increasingly at international scientific meetings. But in my view the prioritisation should not be done by scientists. They have certain objectives which are not always the same as those of rural farmers. Often we think about the potential commercial application, while neglecting certain crops that play a vital role in subsistence farming, which science could help improve. But there are some clear scientific priorities. Fragile ecosystems, such as desert areas, for instance. They have lots of valuable plants.

Are you saying that deserts contain edible plants that need to be saved? Exactly. There are 800 known edible plant species in the Sahel. We established a new modern gene bank last year on Egypt's Mediterranean coast near El Arish to conserve and use desert species. We are working with Saudi Arabia on that country's desert species for land rehabilitation. In saline coastal areas biodiversity is especially high. If you go to the deserts in the Middle East, the Bedouin will show you places where you will find important medicinal plants. Saudi Arabia has some 320 medicinal plant species. Some are highly endangered. For one species, we found only 12 trees. People talk a lot about halting the spread of deserts, but we are talking about desert development. The desert is a reality. We need to think about how to colonise land with droughtresistant plants.

Apart from rocket salad, what other new crops should we expect to see on tomorrow's dinner tables? Hulled wheat is growing more popular. lt comes from einkorn, an ancient cereal crop of the Mediterranean region, which almost died out. There are only a few remaining cultivated sites of ancient einkorn land races. Once it was seen as the food of the poor and seemed doomed. But now it is becoming an exclusive and fashionable food that people will pay a high price for. I especially recommend biscuits made from it. They are fantastic. I am getting requests for the seeds from all over the world now. But every region has its own possibilities. In South East Asia, it is tropical fruit trees like jackfruit and mangosteen. In South America, the native population has always collected and used indigenous tubers such as ulluco and ahipa. In the Andes, amaranth and quinoa were the only cereal crops until Columbus. From Africa, we are very interested in the bambara groundnut. It's like a peanut only bigger. It grows on the edges of deserts and is very resistant to drought. I have collected it in Nigeria. You can use it to make flour or eat it boiled. lt tastes like both chestnuts and chocolatein fact food manufacturers are looking into using it to replace chocolate in some processed foods.

What other foods do you think are rips for revival? Seakale, a brassica that grows on the seashore, is very promising for pickles, for instance. I think sorrel could revive as a salad vegetable, like rocket. There are many ancient Mediterranean and European fruits that could grow in popularity again. Quince, for instance. When I was a child it was the only jam we had. In England you have sloes, the fruit of the blackthorn tree. Or the fruit of the carob tree. In my father's time, families made juices and sweets for children from their big pods. They still make molasses from them in Lebanon. I think there will be a revival of lost varieties of apples and pears too. In southern Italy, we have a "lemon apple', which originates from a village near where my father was born. Today it is sold at a high price in Rome. These examples all show that there is a moral obligation to preserve the wealth of genetic diversity for future generations.