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Missing in action. Cloned embryos lack proteins (yellow) that guide cell division.

The Problem With Cloning Primates

While governments around the world debate how to prevent human reproductive cloning, it seems that nature has put a few hurdles of its own in the way. In the 11 April issue of Science, a team reports that in rhesus monkeys, cloning robs an embryo of key proteins that allow a cell to divvy up chromosomes and divide properly. The same problem may also thwart attempts to clone humans.

Several groups have tried--and failed--to clone monkeys through somatic cell nuclear transfer, the process by which a nucleus from one cell is extracted and injected into an egg whose own nucleus has been removed. Gerald Schatten of the University of Pittsburgh School of Medicine and others had suspected for several years that something was disturbing cell division in cloned embryos. The embryos seemed normal at their earliest stages, but none developed into a pregnancy when implanted. When the researchers looked more closely, they realized why: Many of the cells in a given embryo had the wrong number of chromosomes. Although embryos can survive for a few cell divisions with such defects, soon the developmental program becomes hopelessly derailed.

To find out what was interfering with proper cell division, the team fluorescently labeled the cell-division machinery in cloned rhesus embryos. The researchers saw that the mitotic spindles, which guide chromosomes to the right place during cell division, were completely disorganized. And two proteins that help organize the spindles, called NuMA and HSET, were missing. It turned out that the spindle proteins are concentrated near the chromosomes of unfertilized egg cells--the same chromosomes that are removed during the first step of nuclear transfer. In most other mammals, Schatten says, the proteins are scattered throughout the egg, and removing the egg's chromosomes seems to leave enough of the key proteins behind for cell division to proceed.

The work "explains why no one has yet succeed in achieving normally developing embryos from human nuclear transfer," says Roger Pedersen of the University of Cambridge, U.K., who attempted human nuclear transfer experiments at his previous laboratory at the University of California, San Francisco. "Primate eggs are biologically different." Moreover, says Schatten, "This reinforces the fact that the charlatans who claim to have cloned humans have never understood enough cell or developmental biology" to succeed.

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Schatten's site