Untangling cloning's most difficult snags

Scientists announce they've found ways to improve their often-low success rate.

Experiments reported today show how to boost dramatically the efficiency of animal cloning.

The researchers say this won't lead immediately to a cloning zoo. But it will give scientists a powerful tool with which to study the biological snags that have made mammalian cloning, in particular, an almost no-win exercise.

Hype over a handful of cattle, sheep, and monkey clones has obscured the fact that few clones make it to healthy adulthood. Most perish before or shortly after birth. Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass., calls this low productivity "one of the major challenges of mammalian cloning."

Now, cloning experiments with mice in his laboratory and at the University of Hawaii in Honolulu have a 21 percent success rate - compared with previous success rates of a few percent or less.

The techniques Dr. Jaenisch and his colleagues report in today's issue of Nature Genetics boil down to using fresh cells from embryos - so-called stem cells - and careful timing of key steps in the cloning process.

His research indicates that - at least for mice - it's better to use genetic material from stem cells than to try to reproduce adults.

It's too soon to tell whether or not this will be a step toward an eventual ability to clone humans. Such research could reveal new obstacles on that path.

The Whitehead announcement notes that "the federal government and most scientists believe human cloning to be unethical." But it adds that "improving cloning technology could have real benefits in agriculture and animal husbandry, as well as in biomedical research...."

Much of the recent excitement about cloning arose because the clones were derived from mature animals - inspiring fanciful visions of adult humans cloning themselves. In stem-cell experiments, by contrast, scientists scoop the nuclei containing the genetic instructions out of both a donor cell and an egg cell. They then place the donor-cell nucleus into the egg cell and plant the egg in a surrogate mother. The egg is then supposed to develop through embryonic and fetal stages.

Eventually, an infant will be born and grow into an adult. Only then, can scientists call the cloning successful.

The new experiments indicate that scientists should be picky in selecting donor cells for several reasons. For one, many strains of laboratory mice are inbred. Cloning with their stem-cell material was a total failure. Stem-cell nuclei from mice that were not inbred produced a 21 percent success rate. Jaenisch's Whitehead colleague, William Rideout, says this indicates that successful cloning may depend partly on the genetic diversity of the donors.

Another factor that may have hampered mammalian cloning is the age of the donor cell.

In addition, adult cells are specialized for specific functions, Jaenisch notes, making it harder for the egg cell to "reprogram" the donor-cell nucleus. In other words, the egg cell has to make the donor cell think it's young again so it can start over as an unspecialized unit that can develop into an embryo. It's much easier for nuclei from stem cells to start afresh than for cell nuclei from adults to be born again.

With the new ability to readily produce mouse clones, scientists can make in-depth studies of the importance of such factors.

Meanwhile, there's a bonus for geneticists. Whitehead experimenters inserted a foreign gene into some of the donor nuclei. The resulting mouse clones carried that gene. Dr. Rideout noted that "transgenic science is an important research tool because it allows us to insert mutations in a gene and study how [this] affects the whole animal." Now geneticists have a new and faster way to produce these transgenic mice.

(c) Copyright 2000. The Christian Science Publishing Society

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