The FDA Reviewer Who Refused to Approve Thalidomide

Frances Oldham Kelsey had been at the FDA for one month in September 1960 when an application for a new sedative called Kevadon landed on her desk. Richardson-Merrell wanted to sell it as a tranquilizer and morning-sickness drug. The active ingredient was thalidomide. It was already on shelves in West Germany, the UK, Canada, and twenty-odd other countries. The company expected a rubber-stamp.

They did not get one. Kelsey, a Canadian-trained pharmacologist with a PhD as well as an MD, read the file and decided the safety evidence was thin. The animal data was poor. The clinical reports were anecdotes. There was nothing on chronic toxicity. She sent it back and asked for more.

Under the law then, the FDA could only refuse action for 60 days at a stretch. After 60 days, if no objection was filed, the drug was approved by default. So Kelsey filed an objection. Then another. Then another. Richardson-Merrell complained to her superiors and called her stubborn and unreasonable. She kept asking for the data.

In November 1961, the German pediatrician Widukind Lenz and the Australian obstetrician William McBride independently reported that thalidomide taken early in pregnancy was producing severe limb defects in newborns. More than 10,000 children worldwide were eventually affected. The American total was a few dozen, almost all from the company's pre-approval samples handed out by doctors.

The story broke on the front page of the Washington Post on July 15, 1962. Kennedy gave Kelsey the President's Award for Distinguished Federal Civilian Service in August. By October, Congress had passed the Kefauver-Harris Amendment, which required companies to prove drugs not just safe but actually effective, and gave the FDA authority over clinical trials. The modern drug-approval system grew out of one reviewer who would not stop asking questions.