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A Force of Nature? New Scientist 17 Jan 98 (Ed)

ALL it took was a few words from one maverick scientist to send the media into a flat spin. Richard Seed, a Chicago-based physicist, brought the world to his door last week when he announced that he plans to open a clinic to produce cloned human babies for desperate couples. Of course, he is extremely unlikely to succeed because he has neither the money nor the team of experts needed for the challenge. But, like other mavericks throughout history, he has forced us to think about his plans to do what many would wish was the undoable. Which is precisely the point. Too many bits of the technology needed to produce a human clone are already being developed for other, widely accepted medical treatments or for research purposes. And because human cloning cannot go on looking difficult for long, President. Bill Clinton and the doctors and scientists demanding a worldwide ban on cloning won't be able to delay someone, somewhere, making a success of it. Techniques to transfer a nucleus from one cell to another are being perfected using monkeys because it may be easier to study deadly diseases such as AIDS using standardised animals (see p 4). And couples are already benefiting from techniques not dissimilar from those that could be used in cloning. Only last July, The Lancet reported that an infertile woman gave birth after one of her eggs was treated by adding cytoplasm from the eggs of a younger donor and fertilising it with sperm from the infertile woman's husband.

In this case, cytoplasm was transferred from a donor to rejuvenate another woman's egg and the happy outcome was that a couple were able to have their own biol,)gical child. Technically, it is not a vast leap to transfer a human nucleus. And as the furore over Seed's proposed clinic demonstrates, there will be people who want a clone. Experience worldwide shows that infertile couples may go to enormous lengths to pass on their genes. Given that the alternative is to accept a donation of sperm or egg, and so have a child that is genetically half their own, there will be couples who would prefer to try for a child who is a clone of one of them. After all, they can argue that nature already produces twins. And while identical twins of the same age catch the eye, would anyone notice that a middle-aged person's baby was really a clone? Age changes people. Changes in attitude towards reproductive technologies can be very fast. Less than a century ago, people were appalled by the artificial insemination of animals. Twenty years ago, the birth of the first test-tube baby created a storm of controversy. Now IVF is just another acronym in the dictionary. Our first reactions are often emotional. Maverick though he may be, Seed has made us aware that demand for cloning will come from the powerful desire for humans to have their own children. It is easy to dismiss Seed. It is another thing to argue against human nature.

Crossing the Line New Scientist 17 Jan 98

PEOPLE will be cloned and laws banning the practice will do little to slow progress towards that milestone, experts in reproductive medicine are predicting. Richard Seed, the Chicago physicist who stunned the world last week by saying he would open a cloning clinic, is widely seen as a vocal maverick who is unlikely to clone a person in the foreseeable future (see below). But mainstream researchers are quietly developing techniques on primates and human egg cells which should ultimately bring them to the brink of human cloning. While the researchers involved don't intend to start cloning people, private reproductive clinics will then be tempted to cross that line. "I understand there's already a bit of a race among cutting-edge IVF clinics to get into this technology," says Don Wolf of the Oregon Regional Primate Center in Beaverton, who works on the cloning of primates. The technology that underpins cloning is nuclear transfer, where chromosomes from a donor cell are inserted into an egg cell that has been stripped of its own genetic material. In the case of Dolly the sheep, scientists at the Roslin Institute near Edinburgh used an adult breast cell as a donor. Last week, while commentators debated the moral implications of Seed's plan, the Roslin team stressed health and safety objections. Harry Griffin, the institute's assistant director, says that to make Dolly, 277 cloned cells were implanted into temporary surrogate mothers to identify those that began to develop normally. Only 29 did, and these were then transferred to more than a dozen ewes. Dolly was the only one of these embryos that survived gestation or that didn't die shortly after birth from cardiovascular or other developmental abnormalities. "This is the sort of information that people like Richard Seed don't seem to read," Griffin says. But nuclear transfer technology is advancing rapidly, Wolf notes. And as it does, the unacceptable risks outlined by Griffin will diminish. "If there's a line in the sand defining the risk, then it will be shifting all the time," argues Wolf. Last year, Wolf and his colleagues in Oregon and Texas announced that they had cloned two rhesus monkeys from 106 attempts using cells taken from enibrvos as donors. Wolf aims to trv cloning froni niore developed cells later this year. The US government's National Ilisti tutes of Health is funding his research because it could lead to a supply of genetically identical primates to help standardise research into AIDS and other diseases. And while Wolf has no intention of working on human cloning, he says: "If we can do this in monkeys, most people will see the significance of that to humans." In fact, some researchers are already transferring nuclei from adult human cells. Zev Rosenwaks, a reproductive ocrinologist at the Cornell 4edical Center in New York, is trying to understand the cause of serious chromosomal defects. His group is transferring nuclei from damaged cells into immature healthy eggs to find out whether they will then divide nor mally and form healthy mature eggs. "If the real problem lies outside the nucleus, we might be able fix those defects," he says. Rosenwaks adds that the same technique could be used to grow eggs in culture for women who have damaged ovaries. They could then be mixed with sperm to create a viable embryo. Again, Rosenwaks is not interested in cloning. But if he perfects his technique it would be possible for someone else to apply his nuclear transfer methods to mature egg cells rather than immature ones that have sill go through their final cell division-and so produce human clones. Lori Andrews, an expert on the legal aspects of reproduction at Chicago-Kent College of Law, claims that many clinics in the US already have the equipment needed to start cloning. She fears that some may try to do so before the risks have been reduced to an acceptable level. That possibility is what President Bill Clinton's proposed five-year moratorium on huntan cloning, now being considered by Congress, is supposed to prevent. But some experts predict that legislation won't halt the march towards human clonesparticularly as human cloning may remain legal in some countries. "You can make cloning against the law but I think people will try anyway," says Jon Gordon of Mount Sinal Hospital in New York, an expert on the production of transgenic animals. "They'll do it because if they do, they'll never be forgotten." Philip Cohen, San Francisco

17 January 1998

AT FIRST sight, Richard Seed seems a serious contender in the race to produce the first human clone. He trained as a physicist, but turned to reproductive technology 20 years ago when he founded a company to transfer embryos from prize cows to surrogate mothers. Then, in the 1980s, he launched a company called Fertility and Genetics to apply the technique to people, using it to move fertilised eggs from healthy women, inseminated several days before, to those with fertility problems. That effort resulted In publications in The Lancet and The Journal of the American Medical Association, with one 1984 JAMA paper (vol 251, p 889) reporting the birth of a healthy child. At the time, this embryo transfer was a competing technology to IVF, but it never caught on. "Seed has enough credentials to make you listen," says Lori Andrews, an expert on the legal issues surrounding reproduction at Chicago-Kent College of Law. "But so many people are far ahead of him." In interviews last week, Seed did not acknowledge that cloning a person would pose a far greater challenge than his previous work. This is in character, says Maria Bustillo of the South Florida Institute for Reproductive Medicine in Miami, a coauthor on some of his papers "He was always kind of eccentric with a lot of grandiose ideas, but I'm not worried. He's not capable of pulling this off".