Drugs approved for use in pregnant women have been adequately tested for effects on fetal development.

In November 1960, a physician at the pharmaceutical company Richardson-Merrell filed an application with the United States Food and Drug Administration seeking approval to market a drug called thalidomide under the trade name Kevadon. The application ran to hundreds of pages. The assigned reviewer was Frances Kelsey, a physician and pharmacologist who had joined the FDA just six weeks earlier. It was her first assignment.

Thalidomide had been approved in West Germany in 1957 under the brand name Contergan, and by 1960 it was being sold in forty-six countries. The drug's West German manufacturer, Chemie Grünenthal, had promoted it as exceptionally safe, safer, they claimed, than aspirin. Sedatives at the time carried real risks of overdose, but thalidomide appeared virtually impossible to overdose on. It was prescribed to people who had trouble sleeping, to patients with anxiety, and increasingly to pregnant women suffering from morning sickness. The drug crossed the placenta. No one had tested what happened when it did.

Kelsey was not immediately certain what was wrong with the Richardson-Merrell application, but something bothered her. The clinical data were thin. The company had relied heavily on studies conducted by its own employees and on correspondence from European physicians, which was difficult to verify. She wrote back requesting more information. The FDA's regulatory framework at the time allowed the agency to delay approval for sixty days by requesting additional data; after that, if the agency did not formally reject the application, approval was automatic. Kelsey used the mechanism repeatedly, writing for more information every sixty days for over a year. Richardson-Merrell's representatives visited the FDA and wrote increasingly frustrated letters. Kelsey did not relent.

In November 1961, a pediatrician named Widukind Lenz stood before a medical conference in Düsseldorf and presented something he had spent months assembling: a pattern. Across West Germany, an unusual cluster of infants had been born with severe limb defects, phocomelia, a condition in which the long bones of the arms or legs are absent, leaving hands or feet attached near the shoulder or hip like flippers. Phocomelia had been vanishingly rare before 1957; now Lenz was counting cases in the dozens, then hundreds. He had interviewed the mothers. Nearly all of them had taken thalidomide during early pregnancy.

Lenz published his findings with K. Knapp in the Deutsche Medizinische Wochenschrift in 1962. By then, thalidomide had been withdrawn from European markets. The final count of children born with thalidomide-caused defects exceeded 10,000, with West Germany alone approaching 5,000. Thousands of others died before birth.

The United States was largely spared. Kelsey's repeated requests for data, which Richardson-Merrell had experienced as bureaucratic obstruction, had held the drug off the American market long enough for the European evidence to accumulate. Kennedy presented her with the President's Award for Distinguished Federal Civilian Service in August 1962. She was the second woman to receive it.

Congress moved quickly. The Kefauver-Harris Drug Amendments, signed into law on October 10, 1962, fundamentally transformed the FDA's regulatory authority. Before thalidomide, drug manufacturers were required to demonstrate only that their products were safe for their intended use. After the amendments, they were required to demonstrate both safety and efficacy through adequate and well-controlled clinical investigations. The amendments also required informed consent from patients participating in drug trials, and they extended FDA oversight over drugs being distributed to physicians as "investigational."

The assumption that thalidomide had displaced, that regulatory approval constituted adequate assurance of safety in pregnancy, was not the result of negligence alone. The regulatory architecture simply had not been designed with fetal pharmacology in mind. Thalidomide revealed the gap, and the law was rewritten to close it.