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Cloning harbors serious, hidden problems, scientists say By GARETH COOK ©2001 THE BOSTON GLOBE Since the birth of Dolly, the first cloned sheep, scientists have made stunning progress, creating seemingly healthy copies of mice, pigs, goats and cows. But Friday, almost five years to the day since Dolly's birth, a team of scientists will announce evidence that these creations of modern science can harbor serious hidden problems in their genetic code, raising new concerns about plans to create a cloned human. The finding, reported in Friday's issue of the journal Science, could explain why so many clone pregnancies fail, and why some cloned animals suffer strange maladies in their hearts, joints and immune systems. And the research, which focused on how cells interpret their genetic instructions, suggests cloning causes further problems that have so far evaded detection. "There are almost no normal clones," declared study author Rudolf Jaenisch, a professor of biology at MIT. The announcement comes at a crucial time, with Congress considering sharp new limits on cloning technology, and under pressure from a range of religious groups, biomedical companies, and patients groups. Current cloning techniques could be used to create a human clone -- a person, the report hints, who could have a host of unpredictable medical and developmental problems. The same technology, however, can also be used for "therapeutic cloning," a process that creates healthy copies of a patient's cells -- not whole beings -- and could eventually be used to treat diabetes, Parkinson's disease, and many other disorders. Some geneticists worry that in the political fight over cloning, these findings could become ammunition against not only human cloning, but also therapeutic cloning. "This is exactly the kind of paper that can be misunderstood, stopping treatments that could save millions of people from diseases," said Robert Lanza, vice president of research for Advanced Cell Technology, a Worcester-based company that is heavily involved in cloning research and could be put out of business by a broader ban. The authors of the report investigated "gene expression," the vital process in which cells use the parts of the genetic code they need. Different kinds of cells -- the skin, muscles, nerves -- have different genes turned on. This pattern is what determines the identity of the cell. To create a clone, researchers take a cell -- a skin cell, say -- from an animal and then return the pattern of gene expression to its most primitive setting, so it will behave like a fertilized egg cell, ready to grow into a new animal. To accomplish this, biologists transfer the DNA from one cell into an egg cell that has been emptied of its own DNA. The egg cell then seems to reset the gene expression of the injected DNA. From there it will grow into an embryo, and eventually a live animal with a genetic code identical to that of the donor. But the reset doesn't seem to work perfectly. In the research announced Friday, scientists cloned mice and then compared the expression of six genes to normal mice. Of about 40 mice, the vast majority had at least one abnormality, according to another study author, David Humpherys of the Whitehead Institute and MIT. Problems with gene expression can be completely harmless, or instantly fatal, or somewhere in between. But with human cloning, the stakes would be much higher. "This may not be a critical fact in how a cow functions," said Mark Westhusin, a leading cloning expert who is an associate professor at Texas A&M. "But humans have to do more than stand out in a pasture and chew grass." And because an animal has tens of thousands of genes, it would be practically impossible to prove definitively that a particular clone is normal, even if it appears fine at first. Dolly, for example, seemed completely normal before suddenly turning obese. In this study, researchers used embryonic stem cells, a primitive type of cell thought to be especially easy to reprogram. Jaenisch said that the team plans to test clones made from other cells, but expects to find similar problems. He emphasized that the finding did not pose any problems for therapeutic cloning. In this technique, a patient's cell is cloned, resetting it to its primitive state and then allowed to divide for several days, to a pre-embryonic stage. This process yields stem cells, which can then be turned into specialized cells that can be implanted back into the patient. Because these cells are performing specialized functions, small gene expression problems are less likely to pose difficulties, the researchers said. Therapeutic cloning, though, has drawn fire from religious and other groups who argue that the process is tantamount to creating and then snuffing out a new life. Others fear it will make it easier to create the world's first human clone. But "there is no reason to punish innocent patients just because of the chance that someone might abuse the system," said Lanza. Gareth Cook can be reached by e-mail at [log in to unmask] http://www.charlotte.com/topnews/pub/clonning.htm * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn