Cloning confusion

Every cloning pronouncement has one guaranteed ingredient: controversy. This time, Atsuo Ogura (National Institute of Infectious Diseases, Tokyo, Japan) and Rudolf Jaenisch (Massachusetts Institute of Technology, Cambridge, MA) are duking it out. Ogura claims that most of the defects that Jaenisch has seen in his cloned mice were caused by the genetic instability of the embryonic stem (ES) cells that Jaenisch used as a cloning source. In turn, Jaenisch calls Ogura's claims of faithful gene expression “ludicrous” and “unbelievable.” Let the cloning wars continue.

At stake is an explanation of the various defects seen in some cloned offspring. Jaenisch believes that a number of things may be going wrong, but initially he has focused his attention on a subset of developmental genes called imprinted genes. Jaenisch found that a number of these genes were expressed at wildly varying levels in both his ES cells and the cloned progeny derived from these cells.An imprinted gene is defined as one whose expression level varies depending on whether the gene was inherited from the father or mother. Jaenisch did not test parent-specific effects. But Ogura found that his clones expressed the correct allele of a number of imprinted genes: some were produced only from the paternal allele and others only from the maternal. Furthermore, a number of genes showed correct expression levels in cloned fetuses.

All is not sunny, however, even in Ogura's world. The placentas of his cloned mice have variable and generally low expression of a wide range of genes, both imprinted and nonimprinted. Ogura believes that this is a general failure in reprogramming of gene expression, which might make it easier to tackle than the allele-specific effects of imprinting. He is now using gene chip analysis to see if there is any pattern in the misexpression data, and to extend the current analysis. “We must know what is a cloning effect and what is a culture effect and what is a donor cell effect,” he says.

If cloning protocols are improved, deciding whether to allow human cloning will become that much more difficult. But for now, on this point, Ogura and Jaenisch agree. “If the scientific evidence changes we can change our views,” says Jaenisch. “Right now it is totally out of the question.” ▪

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