New theory on the origin of twins.

Identical twins result from tiny genetic mutations within a developing embryo that lead one portion of the embryo to reject the other as foreign, causing the two to split, a researcher proposed last week at a conference of geneticists. Other scientists, while intrigued by this concept, caution that the supporting evidence remains inconclusive and that further studies are needed to confirm the theory's accuracy.

Judith G. Hail, a pediatrician and geneticist at the University of British Columbia in Vancouver, says she has found genetic dissimilarities between two twins that arose from the same fertilized egg. One twin has developed as a dwarf, while the other has attained normal height and body proportions, Hall reported at the Short Course in Medical and Experimental Mammalian Genetics at Jackson Laboratory in Bar Harbor, Maine. She hypothesizes that this difference resulted from a mutation in one part of the embryo that caused it to split, creating two different "identical" twins.

Fraternal twins and identical twins result from two separate processes. In the case of fraternal twins, a woman releases two eggs in one month. The two eggs are then fertilized by two different sperm. The two resulting fetuses are no more similar than other siblings, although they are almost always born together. Identical twins, on the other hand, are known to result from a single egg fertilized by a single sperm.

For years, geneticists have believed that such twins are genetically, as well as physically. identical. But they have had few theories to account for why a single fertilization event sometimes results in two fetuses.

"There really is no substantiated theory as to what causes [identical]. twinning:' says Kenneth Lyons Jones, a pediatrician at the University of California, San Diego.

Hall now proposes that all so-called identical twins are really subtly different genetically and that this difference is what causes the embryo to split in the first place. However, she asserts, physicians would detect the tiny genetic difference only in the rare instance when the mutation responsible for twinning happened to disrupt a crucial gene, leading to a disease in one twin but not in the other.

The dwarf twin from the set Hall studied has diastrophic dysplasia, a genetic disorder thought to result from mutations on chromosome 5. Hall hypothesizes that this dwarf twin arose very early in embryonic development, when a single cell of the embryo developed the mutation spontaneously and the other cell or cells ousted that cell as foreign.

"Some of the cells looked at another and said, 'You don't belong here, get out of here,'" suggests Hall.

Once on its own, the expelled cell developed into a complete fetus-identical to its twin except for the mutation, Hail believes.

Victor McKusick, a medical geneticist at Johns Hopkins University in Baltimore -- and an identical twin himself counters that Hall's theory poses a potentially unanswerable dilemma similar to the question of which came first, the chicken or the egg. "Whether the difference [between the embryo's cells] came first or the split came first isn't clear," he contends.

McKusick suggests that the dwarf twin might have resulted from a so-called somatic mutation in one cell after the two twins had separated. If this mutation occurred early enough - say, at the eight-cell stage - most of the affected twin's cells would later contain the mutation, possibly leading to a medical disorder, he says. McKusick notes that other geneticists have recorded instances in which one of two otherwise identical twins has Turner's syndrome - a developmental disorder that results from having only one X chromosome instead of the normal XX for girls and XY for boys. However, he concedes that Hail "would read other significance into this" as support for her theory,

Linda Corey, a genetic epidemiologist at Virginia Commonwealth University in Richmond, agrees with McKusick. "The [study's] sample size is a little small to draw the type of conclusions [Hall is] drawing," she adds. Corey, who also directs the Virginia state twin registry, says researchers are only beginning to do detailed comparisons of twins' genetic material to look for the mechanism of twinning.

Jones, on the other hand, advocates a wait-and-see attitude. "1 don't think [Hall's theory is] totally off the wall," he says. - C Ezzell