The most reviled drug of the 20th century is, incredibly, on its way to a second act. Thalidomide, used in the late 1950s and early 1960s as a sedative and anti-nausea medication, became the ultimate symbol of pharmacopoeia gone awry. When taken by pregnant women for morning sickness, it caused missing limb parts in the fetus— seal limb, or “knuckles at shoulder-blades,” as Sylvia Plath put it—as well as organ damage and death. Fifty years after the drug’s heyday, the fear it inspired haunts arguments about the safety and regulation of medications like Vioxx and Avandia and even products like sunscreen.

Yet recently, thalidomide has slouched back toward respectability—not for pregnant women, of course, but for some patients with less common skin conditions or cancer.

In the late 1990s, the FDA approved thalidomide for the treatment of a complication of leprosy, with strict rules to protect pregnant women. And in 2006, the agency approved the drug for patients with newly diagnosed multiple myeloma, which is a cancer of the bone marrow. Today, scientists are investigating the drug, and a close chemical cousin, to treat conditions from lupus to psoriasis and even as an immune booster for the elderly. This possibility is especially stunning because it means contemplating widespread usage of this class of drugs in basically healthy people and in a group old enough to recall the thalidomide tragedy firsthand.

That tragedy is a major reason the Food and Drug Administration has as much authority over new drugs as it does today. When thalidomide’s maker, the Merrell Company, submitted its application to the FDA in 1960, a government scientist named Frances Kelsey saw the potential for side effects, distrusted the company’s data, and refused to approve it. While thalidomide caused thousands of harrowing birth defects in Europe and Australia, it did not do as much damage here, a regulatory success which won a PR coup for the FDA and personal glory for Kelsey. (In 1962, she received a Distinguished Medal for Civilian Service from President Kennedy.)

The thalidomide story animated the case for broader FDA powers. So, given the drug’s history, why did the FDA give it another chance in the late 1990s? The agency first approved the drug to treat erythema nodosum leprosum, a complication of leprosy that affects only a small number of patients, which meant thalidomide would not show up in millions of medicine cabinets. The passage of time also helped:An internal FDA survey in 1997 apparently found that among Americans over 45, more than two-thirds knew what thalidomide was, but among those under 45, fewer than one-third did. All of this helped dermatologists to win a small toehold for the drug.

Meanwhile, cancer researchers had also gotten interested in thalidomide. In the 1990s, these scientists were looking for compounds that could inhibit the development of blood vessels, which tumors need to grow. Thalidomide has this effect. (In fact, that is probably how it stymied the growth of normal fetal limbs.) Researchers tested the drug successfully on patients with multiple myeloma. Oncologists soon began to prescribe it off-label, and in 2006, the FDA approved the additional usage. The FDA also approved the related compound lenalidomide.

Thalidomide and lenalidomide’s workings aren’t fully understood, and their cancer-fighting benefit, ultimately, probably has little to do with stunting blood vessel growth, says Martha Lacy, a hematologist at the Mayo Clinic—it was “just fortuitous” that this got the cancer docs started. As they later discovered, the drugs seem to work by boosting immune cells in the body that go after malignancies. Today, the immune effects of these drugs are of interest to researchers working on lupus, psoriasis, Kaposi’s sarcoma, allergic contact dermatitis, graft-versus-host disease, and more.

Most startling, though, is the possibility of giving lenalidomide as an immune boost to healthy seniors. Ed Goetzl, a clinical immunologist at UCSF, has long studied how immune function drops off with age: T-cells get worse at reaching pathogens, worse at multiplying, worse at pumping out defensive proteins and at recruiting other cellular allies—worse, in other words, at virtually everything they do to protect the body. Low doses of lenalidomide, however, seem to reverse this decline. In a small study published this month, Goetzl and his team took T-cells from elderly people and from younger, well-matched controls. When treated with the drug in a Petri dish, the cells of the old acted more like those of the young. This year, Goetzl plans to test whether the drug might help the elderly respond better to flu shots by boosting their notoriously weak immune reactions. It’s even possible that the compound or a related one could someday serve as an immune supplement for the old.

Of course, there are caveats galore, as Goetzl is quick to acknowledge: The work is still in early stages, and no one knows if the apparent immune kick will pan out in clinical trials. In terms of safety, the bar is always higher when giving a drug to healthy people, and lenalidomide can cause blood clots and kidney problems. (With the elderly, at least, the risk of accidental pregnancy and birth defects is off the table.)

Still, for scientists to think of these compounds for broad usage, especially in people who aren’t very sick, represents a profound comeback. “I never expected this class of drugs to have any beneficial effects,” says Goetzl. Thalidomide “always just seemed like a sleeping pill gone bad.” Considering how tough it is to get new drugs approved, though, the lesson of thalidomide is that it makes sense to look back at old ones and their chemical relatives. Even a former villain, put to a new task, can have a second life.

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