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Cult's Bizarre Vision Rekindles Cloning Debate New Scientist 31 May 1997

Philip Cohen, San Francisco

AN INTERNATIONAL religious cult is setting up a company to sponsor research in human cloning. While many biologists dismiss the cult's plans as fantasy, leading bioethicists hope the bizarre episode will awaken legislators in the US and elsewhere to the dangers of failing to regulate cloning technology in the private sector. Human cloning is already prohibited by law in Britain and some other European countries. But the only control in the US is a moratorium on the use of federal funds for human cloning research, backed up by a request from President Bill Clinton for private companies to observe their own moratorium. Claude Vorilhon, who lives near Montreal and is known to his followers as Rael, is scornful of Clinton's request. "The technology is not at all dangerous," he says. Vorilhon announced the formation of the company, called Clonaid, at a press conference in New York last week. Vorilhon's [email protected] movement believes that life on Earth was created by aliens who also achieved the resurrection of Christ by cloning. He says it is now time for humans to emulate their "creators". Besides funding research, Vorilhon says that for $200 000, Clonaid will offer customers a chance to clone themselves-although it gives no guarantee of success. Mainstream biologists do not rate Clonaid's chances of cloning a person very highly. Roger Pedersen, who specialises in reproductive technology at the University of California, San Francisco, believes that peer pressure will prevent scientists from joining the company. "Ostracism is a very powerful tool," he says. But some bioethicists argue that there is no room for complacency about the likelihood of some private organisation-if not a fringe group like the Raelians-attempting to clone a person. "This should be a loud reminder of how ludicrous it would be to leave a loophole to allow private funding of cloning," says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia. American legislators, ethicists and scientists have been at odds as to how to regulate the new technology. Vernon Ehlers, a Republican member of Congress from Michigan, has introduced a bill that would make it a criminal offence to clone a human being. But the bill is by no means certain to pass into law. And Harold Varmus, director of the National Institutes of Health, has argued against rushing into legislation that, if not carefully worded, could outlaw potentially valuable work such as research into cloning human tissue for transplants (This Week, 15 March, p 4). The US has for years restricted federal funding of research into human repro ductive biology. But it has taken a laissez-faire attitude to the private sector. Caplan argues that it would be a serious mistake to continue this hands-off approach when it comes to cloning. He claims that there is now a culture within private clinics that says breaking new ground in reproductive technology comes before asking tough ethical questions. Even university researchers are not exempt from the temptation to rush ahead, Caplan adds. Three years ago, he notes, biologists at George Washington University in Washington DC were exposed as having cloned cells from a human embryo without seeking prior ethical approval from the university's Institutional Review Board. Thomas Murray, a bioethicist at Case Western Reserve University in Cleveland, Ohio, agrees: "Regulation has been very skimpy. And that hasn't always been for the best." Murray sits on the National Bioethics Advisory Commission, which is drafting a report for Clinton on the ethics of cloning. He hopes that it will include a proposal to ban human cloning for several years.

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Potatoes Genetically-Altered to Confer Diabetes Resistance
New Scientist 26 July 1997

BY TINKERING with the genetic make-up of potatoes, Canadian researchers ma have discovered a painless way to preven people developing diabetes. Their genetically-engineered potatoes can protec mice from the onset of a form of diabete known as type 1 Type 1 diabetes develops when th body's immune system mistakenly attack proteins including one called GAD o certain cells in the pancreas. These cell called eyelet cells, produce insulin, whic is essential for maintaining correct level of sugar in the blood. Once they ar destroyed, regular insulin injections are th only way to avoid serious illness.

Scientists have been looking for a way to treat the disease by stopping the immune system from killing eyelet cells. Many studies have focused on the idea of oral tolerance-that regularly eating large amounts of GAD could prevent the immune system from attacking the protein. The problem has been that it is difficult to manufacture GAD in bulk. A team of researchers led by Anthony jevnikar of the University of Western Ontario believe they have the answer. They inserted the gene that codes for GAD into the DNA of potato plants, which grew to produce potatoes with high levels of GAD. For several months, the team fed these potatoes to mice that had been specially bred to be highly susceptible to diabetes. "These mice are a good model of what happens in type I diabetic people," says jevnikar. "They have the same pancreas structure and immune response." In this month's Nature Medicine (vol 3, p 793), the team reports that only 2 of the 12 mice fed with the potatoes developed the disease, compared with 8 out of 10 untreated control mice. "Our ultimate goal is to see if this method will work in humans," says Jevnikar. "This is an important combination of two new technologies-oral tolerance and genetic manipulation," says Marco Londei.

Cow clones support Dolly NS 11 Jul 98 4

TWO calves thought to be cloned from the same adult cow have been bom in Japan. If DNA analysis confirms their origin, the calves will provide the long-awaited confirmation that Dolly was not a fluke. The calves were bom at the Ishikawa Prefecture Livestock Research Centre on 5 July-40 days premature. As New Scientist we to press they were both healthy, but their surrogate mother died after the birth. Last November, researchers at Kinki University took cells from the oviduct of a freshly slaughtered cow. They cultured these cells briefly and then fused them with cow eggs that had been stripped of their nuclei. Some began to divide to form embryos, and were implanted into cows one of which were declared pregnant In January. Yuklo Tsunoda, who led the Kinki team, now aims to analyse the clones' DNA: "That will take about two weeks. We have to be sure the cells and their cultures were not mixed up with others." Grahame Bulfield, director of the Roslin Institute near Edinburgh, where Dolly was created, hopes these studies will verify that adult animals can be cloned. "You really want another laboratory to do it in anottw species," he says. Peter Hadfield, Tokyo, and Andy Coghlan

Organs without Donors NS 11 Jul 98 4

IT'S A transplant surgeon's dream: an endless supply of organs and tissues neatly matched to their recipients. And it might happen, if a radical new technology works. The technology exploits the nuclear transfer technique that underpins cloning' A cow egg stripped of its own nucleus would be fused with a human cell to create an embryo that begins to grow in the test tube but is not viable in the long run. Next, embryonic stem (ES) cells would be taken c from that embryo: crucially, these cells can develop into a wide range of tissues. The techniques need further work, but New Scientist has learnt that many of the key steps have quietly been accomplished. "Our work is looking very promising," says Jose Cibelli of Advanced Cell Technology (ACT), a biotechnology firm in Worcester, Massachusetts. Among the earliest medical payoffs could be the production of nerve or heart muscle cells for transplant. But ultimately, entire organs might also be created. Because these tissues and organs would be cloned from the patient's own cells there should be little problem with immune rejection. This could provide a desperately needed solution to the chronic shortage of donated human organs. Everything else proposed so far has serious drawbacks. Animalto-human transplants, for example, may require extensive genetic engineering to make sure that the human immune system doesn't destroy the animal's tissues. Another approach is to harvest ES cells from human embryos (This Week, 19 July 1997, p 4). The right 'growth factors" could persuade human ES cells to develop into issues and organs in vitro. But they would be no more closely matched to a recipient than an ordinary donated organ, and the cells isolated so far come from aborted fetuseswhich many people find repugnant. When Dolly the sheep was cloned, the possibility of cloning human organs for transplant soon surfaced. Media comment focused on the ghoulish idea of creating clones-perhaps with their higher nervous functions destroyed-to provide a set of perfectly matched organs. Harvesting ES cells from an early-stage embryo created by cloning, and growing tissues and organs in the lab, would be more likely. But that would still mean creating, and then destroying, a viable human embryo. "I'd have to search my conscience if that embryo had the potential of making a full human being," says Joseph Jerry, a developmental biologist at the University of Massachusetts in Amherst. In any case, human eggs are in very short supply. So Jerry and his colleagues have turned to cow eggs, which are plentiful. Ironically, their progress relies on the failure of a technology developed by a team led by Neal First of the University of Wisconsin at Madison. Earlier this year, First showed that adult cells taken from a wide array of mammalian species could be fused with stripped of their own nuclei to e embryos that begin to develop . He hoped this could provide y to clone endangered species s Week, 24 January, p 5). But he has now found that these embryos all stop developing before organs start to form. But nonviable embryos made by fusing human cells with cow eggs stripped of their nuclei might be what researchers like Jerry are looking for. "For human tissue production, you want a system at you could guarantee would t make offspring," says First. key to the technique would extracting ES cells from the yo before it stops developing. cells are notoriously difficult to obtain, however, and only in mice had they passed the ultimate test: injection into early embryos and subsequent development into a wide range of tissues. But Jerry and his Amherst colleague Jim Robl, working with Cibelli and Steve Stice at ACT and others, have found that cells taken from early bovine embryos also pass this test (Nature Biotechnology, vol 16, p 642). In the same paper, they report extracting similarly potent stem cells from embryos cloned by nuclear transfer from fetal bovine fibroblasts-cells found in connective tissues. And in work not yet published, ACT has used the same trick to produce ES cells from the fibroblasts of an adult cow. The next step is to see whether stem cells can be taken from an embryo created by fusing a human cell with a cow egg. Cibelli declines to discuss ACT's plans, but the company has applied for a European patent involving the fusion of human fibroblasts with cow eggs. First's team is already trying to make ES cell lines from embryos created by cross-species nuclear transferalthough the researchers haven't yet attempted a fusion with human cells. But even if the experiments work, will people accept the idea of transplant organs made from a human-cow cell fusion? "If something stops this work, it won't be technical problems, it will be legal or ethical issues," says Cibelli. Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia, agrees that the technique will be controversial. But as it doesn't create viable human embryos, it avoids the worst of the ethical quagmire, he argues. "I think scientists have to take a deep breath and start explaining that to legislators and the public," he says. Philip Cohen