Wednesday, February 18, 2004

When is a Group of Cells a Baby?

A rose is a rose is a rose, even if ? like many commercial plants ? it is essentially a clone. But is a normal human blastocyst, a microscopic bubble of proto-life that forms about five days after sperm meets egg, the same as a cloned blastocyst ?

That may seem an arcane technical question in the debate about human cloning, reignited last week with the announcement by South Korean scientists that they had cloned a human embryo and harvested embryonic stem cells from it. But scientists, politicians and bioethicists have been grappling for years with the biological and moral subtleties encapsulated by that tiny dot of tissue.

The future of human therapeutic cloning in this country ? the laws governing it, the knowledge to be gained from it, the ethical costs of doing it and the medicines it might eventually bestow ? may hinge on how society views that question.
The South Korean group did not try to create a baby. The promise of therapeutic cloning, still theoretical, derives from the following premise. By introducing the DNA of an adult human cell into a human egg whose nucleus has been removed, the resulting hybrid cell can be induced to behave like a fertilized egg. Like a normal embryo, it begins its development as a single cell, but it contains the genetic payload ? and, presumably, the immunological identity ? of the adult patient. Treatment, not children, is the ultimate point of the exercise.

But cloned embryos may not be genetically equivalent to normal embryos. Dr. Rudolf Jaenisch, an expert on the genetics of animal cloning at the Whitehead Institute for Biomedical Research in Cambridge, Mass., has published studies showing that cloned mice are riddled with genetic abnormalities. Those glitches suggest that a cloned embryo would have "little if any potential to ever develop into a normal human being."

When an egg cell reprograms the DNA of an adult cell during a cloning experiment, Dr. Jaenisch said, the process is probably incomplete ? raising the possibility that genes in the cloned embryo are not activated (or "expressed") at the right time, in the right amount, and properly suppressed when not needed.

Gene regulation of this sort is especially significant in a class of genes known as imprinting genes, which play a crucial role in fetal development. "We think that 30 to 50 percent of imprinted genes are not properly expressed in clones," Dr. Jaenisch said, "and imprinting genes are mostly important for pre-natal development."

As a result, he said, the South Korean approach may be "useful for therapy, but not useful for cloning." Dr. Daley, who with Dr. Jaenisch published one of the first animal experiments suggesting the promise of therapeutic cloning, said, "All of the concerns and risks of mammalian reproductive cloning have not changed with this paper.
In addition to being a notoriously inefficient procedure, animal cloning has produced many animals with conspicuous developmental problems, like respiratory illnesses and overly large placentas. Dolly the cloned sheep suffered from premature arthritis before dying last year. Such genetic dysfunction is one reason for nearly unanimous scientific opposition to reproductive cloning. As Dr. Daley put it: "As a scientist, I would be willing to support a ban on reproductive cloning, if it allows us to pursue legitimate therapeutic research. That is the most rational way of approaching the debate."

But Dr. Jaenisch also made a distinction between cloned embryos and the kind of blastocysts formed during normal reproduction, including embryos fertilized in vitro. "When you really think about an I.V.F. embryo that rests in a deep freeze, it only has three fates," he said. "It can be destroyed, it can be implanted into a woman or it can be converted into embryonic stem cells. When you make embryonic stem cells, you do destroy an embryo, and that is an ethical issue.

"Cloned embryos also have three fates. "They can be destroyed, they can be used to make normal embryonic stem cells tailored to the needs of patients, but they cannot make a normal baby. In my opinion, the destruction of a cloned embryo to make embryonic stem cells poses less ethical problems than the destruction of frozen embryos in the I.V.F. clinic."

Dr. Thomas H. Murray, president of the Hastings Center in Garrison, N.Y., says this scientific distinction has moral import. "What are the ethical implications if embryos created in this way are not viable, or severely impaired?" he asked. "If Rudy Jaenisch is right, if embryos created by cloning are a fairly abnormal ball of cells, that would compel us to think very hard about what moral meaning to attach to such an entity."

Such a scientific distinction, Dr. Murray also noted, could "complicate" a split in the anti-abortion movement that emerged several years ago during the debate over stem cell research and cloning. Several prominent abortion opponents, including Senator Orrin G. Hatch, Republican of Utah, supported federal financing for stem cell research; Mr. Hatch has also co-sponsored legislation allowing therapeutic cloning while prohibiting reproductive cloning.[Nitpicker emphasis]

As the article intimates, scientific knowledge as well as technology, has a ways to go before human reproductive cloning will be a reality. What of the Human Genome Project? Remember how it was going to result in the identification of all these 'disease' genes as well as diagnostic tests and therapeutic treatments? In reality, as most scientists (without financial/professional gain from the project) would acknowledge, knowing the sequence of the 3 billion basepairs was much ado about not very much. Knowing the sequence of a given gene tells little of its function and nothing of the regulation of its expression. Distinctions are important and hopefully with respect to therapeutic cloning, they will be made clear so that scientific advances in the U.S. will not be hampered by the misunderstanding of anti-abortion proponents in Congress.


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