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Duboule concedes that "this is not even a real hypothesis," just a hunch, and that testing it will not be easy. One problem, contends Harvard's Tabin, is that Duboule and his colleagues studied "the wrong fish." Zebrafish are prolific and easy to raise under laboratory conditions, but they are advanced in evolutionary terms. A study of more primitive sea life, such as sharks or sturgeon, might yield greater amounts of evolutionary information; even better subjects would be lungfish and coelacanths, mysterious, nearly extinct creatures that lurk in the ocean depths and are the living fish closest to the fishlike ancestors of four-legged animals.
Further studies are needed to convince scientists that Duboule and his colleagues have correctly solved the fins-to-feet riddle. Other factors could be involved as well, including homeobox genes that are not Hox genes (that is, they do not affect the overall structure of an animal). Last year Sean Carroll, a developmental biologist at the Howard Hughes Medical Institute in Madison, Wisconsin, showed that a homeobox gene involved in insect-limb formation also controls the genetic signals that paint spots on butterfly wings. In essence, says Carroll, butterflies use an old gene to perform a new trick. "Evolution did not have to invent new genes," he observes. "One basic toolbox gives nature enormous potential for diversity."
The drawback for scientists is that nature's shrewd economy conceals enormous complexity. Researchers are finding evidence that the Hox genes and the non-Hox homeobox genes are not independent agents but members of vast genetic networks that connect hundreds, perhaps thousands, of other genes. Change one component, and myriad others will change as well-and not necessarily for the better. Thus dreams of tinkering with nature's toolbox to bring to life what scientists call a "hopeful monster" -- such as a fish with feet -- are likely to remain elusive. Scientists, as Duboule observes, are still far from reproducing in a laboratory the biochemical artistry that nature has taken millions of years to accomplish.