In 2006, he and a team of collaborators began a survey of the metabolites of thalidomide. William D. Figg of the National Cancer Institute purified them, and Dr. Vargesson and his colleagues tested them in chick embryos. As they described in a report last year, they found that only one metabolite they tested, known as CPS49, caused the chicks to fail to develop wings.

The scientists also noticed something else about CPS49: within minutes of being injected into an embryo, it started killing developing blood vessels. Dr. Vargesson and his colleagues proposed that the death of these new blood vessels stopped the limb bud from taking its final shape.

In a healthy embryo, patches of cells along its sides swell into buds that stretch out into arms and legs. The proliferation of the cells triggers genes in the limb bud, which make proteins that sculpt the limb. CPS49, Dr. Vargesson argued, starves the limb, causing many cells to die. The surviving cells do not get the proper signals and fail to develop.

This model could account for how thalidomide could have such a drastic effect on limbs without causing much damage elsewhere in the body. Limbs develop relatively late, beginning about 23 days after the start of pregnancy. An embryo exposed to thalidomide at that point would suffer damage to its limbs, Dr. Vargesson said, while the rest of it would suffer less damage because its blood vessels were already mature.

Even if Dr. Vargesson’s model turned out to be right, it was missing some key pieces. In order for thalidomide to do its damage, it must grab on to some particular kind of molecule in the embryo.

To find that target, Dr. Hiroshi Handa of the Tokyo Institute of Technology and his colleagues coated microscopic beads with thalidomide. They then immersed the beads in various proteins. As they report in the current issue of Science, a protein known as cereblon latched on tightly to the thalidomide.

“We were very surprised,” Dr. Handa said. While scientists have identified scores of genes involved in the development of arms and legs, no one had ever suspected cereblon of playing a role. In fact, no one was sure what cereblon did.