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Experts detail obstacles to human cloning

When it comes to human experimentation, the answer to cloning is rapidly becoming "no" among industrialized nations. Scientists say cloning poses not only ethical but also technological problems.

"Most of us have a strong investment in the notion of individuality--that each of us is different from the other, that the egg and sperm are unique that make an embryo," said Ruth Hubbard, professor emeritus of biology at Harvard University and a member of the Council for Responsible Genetics, at a May 6 panel discussion at MIT on the ethics of cloning. "The notion that we can produce copies is offensive to a lot of people, but it also is not true, because the cytoplasm outside the nucleus is different, the person gestating the embryo is different, and the baby's environment is different after birth. So the notion that you could reproduce yourself is totally false."

The efficiency of cloning is not high, said Professor of Biology Rudolf Jaenisch, who gave the annual MIT Sigma Xi lecture entitled "Ewe-genics: Dolly and the Cloning of Mammals" on Monday.

"The older the mother, the less efficient the cloning. Dolly's mother was six, so Dolly is probably six and a half. Cloning Dolly would prove even less efficient," said Professor Jaenisch, who also is a member of the Whitehead Institute.

Still, he said the sheep experiment could be done in humans. "It might be done by another society. But it should be regulated."

Professor Hubbard was joined by Karl Ebert, reproductive physiologist and a professor at Tufts University's medical, dental and veterinary schools, and Professor George Annas, chair of the Health Law Department at the Boston University School of Public Health. Jonathan A. King, professor of biology at MIT, moderated the panel discussion, which was co-sponsored by the Technology and Culture Forum and the Lecture Series Committee.

The issue of human cloning came into sharper focus in February, when Scottish scientists said they had cloned a sheep named Dolly. The feat quickly turned attention to issues surrounding cloning of humans, as a Time cover story asked, "Will There Ever be Another You?" The April 7 cover of The New Yorker showed Albert Einstein's face on the body of four sheep. Some scientists speculated that parents might want to clone a beloved child who has died.

"The reaction should be horror. Parents do not have the right to collect cells from a child to reproduce that child," said Professor Annas. "The basic public outcry against human cloning is correct." He said Europe is ready to pass a law against human cloning, and President Clinton's bioethics committee is preparing a recommendation for the United States.

There are now two meanings to the term "cloning," Professor Hubbard explained. The first is embryo splitting, in which an embryo with multiple cells that are identical is disaggregated and implanted into mothers to generate genetically identical animals. This has been done for years with animals and tried once in humans. (That experiment created a huge outcry and hasn't been repeated as far as we know, she said).

The second method is nuclear transfer, a recent form of cloning in which scientists take a cell of an early embryo and put the nucleus into an egg cell whose nucleus has been removed, causing that cell to divide. This has been done in animals but not in humans.

The new twist on cloning that involves Dolly is that the nucleus was taken not from an embryonic cell, but from the cell of a mature sheep. The new trick is to reprogram the genetic information from the cell of specialized tissue of a mature animal--for example, mature breast tissue which normally does not reproduce--so that the recipient cell reproduces.

"But nucleus transfer methods are not cloning in the sense that they do not produce an organism identical to the original animal, because the egg cytoplasm is different," said Professor Hubbard. "There is a notion that DNA in the nucleus determines all of what we are, but this is not true. A lot happens in the interaction of the egg with the cytoplasm."

Professor Ebert agreed that nucleus transfer is not true cloning because it involves a mixture of nuclear DNA and the accompanying genetic DNA just outside the nucleus.

When Dolly was introduced in the February 1997 issue of Nature, the sheep pictured on the cover had one black hoof. "This apparently is the result of mitochondrial DNA, because the mother did not have a black hoof," said Professor Annas.

Although Dolly was four months old when she was announced to the world, it is not clear how old she really is, since the nucleus that created her came from a mature ewe, said Professor Hubbard. "She may be pre-programmed to the mother's age. We'll only be able to tell her age when she gets older," she said.

Professor Ebert said Dolly also is not a true clone because she did not come from an embryo, but from a somatic cell nucleus in the mammary gland of an old female sheep.

Creating Dolly was not an easy task. It took 277 tries to get only 27 embryos to develop. Of those embryos, only one produced the so-called cloned sheep. "So I don't think this is as frightening as it seems. I don't think that anyone anywhere today is in a position to `clone' a human," said Professor Hubbard. "It's not just that the societal issues are overwhelming; the scientific issues are overwhelming as well."

When science develops something like cloning that changes human life, the burden of proof should be on the scientists, not the regulators, argued Professor Annas. "And there's no argument for cloning human beings."

He said part of the reason for naming the sheep Dolly was to diminish fear and distance her from the Frankenstein myth, where the scientist couldn't name his creature and thereby did not take responsibility for it.

But even more than the ethical arguments, a lack of commercial opportunities is working against cloning, Professor Annas said. "No one can think of a way to make money doing this."

A larger long-term issue is genetic engineering, which does not require cloning of an entire whole organism. "Most parents want a kid who is better than they are. And there is money in producing a better human--a taller kid, for example," he said.

A version of this article appeared in MIT Tech Talk on May 14, 1997.

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