Cloned sheep, cows, cats, pigs and human embryos have made regular appearances in the headlines lately. Less widely appreciated is how very difficult it is to successfully clone a mammal. Indeed, the vast majority of cloned embryos fail to fully develop. Now new research could help explain why. According to a report published today in the journal Genes and Development, one gene's activity seems to have an especially significant influence on whether a newly cloned mammalian embryo flourishes or flounders.

Hans R. Schler and his colleagues at the University of Pennsylvania found that expression of a gene called Oct4 correlates strongly with a cloned embryo's progress. Oct4, it turns out, encodes what is known as a transcription factor, a protein that controls the expression of other genes. As such it plays a key role in embryonic development. In fact, an embryo cannot survive without Oct4; likewise, too much or too little Oct4 expression dooms the embryo. When Schler and his team examined Oct4 activity in mouse embryos cloned from adult cells, they found that 90 percent of the clones failed to express the gene at the right time, in the right place and at the right level to permit further development. Thus, aberrant expression of Oct4 can, in theory, almost single-handedly account for the 98 percent failure rate among cloned mouse embryos.

Such fickle gene activity casts further doubt on the viability of reproductive human cloning. But the findings may brighten the future of therapeutic cloning: although only a scant few of the mouse clones made it, these were able to form embryonic stem cell lines. "Embryonic stem cells can be carefully tested prior to being used in the patient," Schler observes. "In reproductive cloning, only the organism provides proof of whether the procedure worked or not."