A sedative already sold in more than 20 countries landed on a new FDA reviewer's desk with a 60-day deadline. Frances Oldham Kelsey refused to approve it because the safety evidence wasn't good enough.
Her repeated refusals kept thalidomide from going on sale across the United States as reports of severe birth defects emerged in Europe. Her path to that decision began years before the application arrived.
A scientist nearly kept out of the field
In 1936, the University of Chicago accepted Frances Oldham Kelsey into its pharmacology program. The professor who sent the acceptance letter assumed Frances was a man and addressed it to "Mr. Oldham."
Kelsey went anyway. She earned a PhD and a medical degree, then joined the FDA as a new drug reviewer in August 1960.
The application that raised a question
A month after Kelsey joined the FDA, the second application to land on her desk was for Kevadon, a sedative made by Richardson-Merrell. Its generic name was thalidomide.
The drug was already a bestseller in more than 20 countries. Doctors were prescribing it to pregnant women for morning sickness, and it was marketed as safe enough for children. Richardson-Merrell expected approval, but Kelsey found that the safety evidence relied mostly on testimonials rather than trials.
She also noticed a British report of nerve damage in adults who had taken the drug. That raised a question about the patients who could be most vulnerable: If thalidomide could damage an adult's nerves, what might it do to a fetus?
Kelsey rejected the application as incomplete.
How Kelsey kept the drug from wider sale
Under the rule described in the case, Kelsey had 60 days to approve the drug or it could go on sale automatically. When Richardson-Merrell resubmitted its application, she rejected it again. Every 60 days for more than a year, she returned to the same answer: not enough data.
The pressure grew. Merrell executives contacted Kelsey and her boss roughly 50 times over 18 months. Sales representatives crowded her office and called day and night. Kelsey later recalled the insults they directed at her:
"Most of the things they called me, you wouldn't print."
Patients were already receiving samples
Kelsey didn't know that Richardson-Merrell had used a loophole for investigational drugs to ship thalidomide in the United States. The scale was substantial:
- The company shipped 2.5 million tablets.
- More than 1,000 American doctors received them.
- Nearly 20,000 patients were given the drug.
- Several hundred of those patients were pregnant.
Kelsey had blocked approval for general sale, but the samples had already reached patients.
Reports from Europe revealed the harm
In late 1961, reports arrived from Europe of thousands of babies born with severely shortened arms and legs, described in the account as "flippers." At least 4,000 children were affected, and countless more pregnancies ended in miscarriage.
Richardson-Merrell withdrew its application in March 1962. In the United States, 17 children were affected, all through the samples. Kelsey's refusal had prevented thalidomide from reaching the country through wider sales.
Recognition and a change in drug regulation
In August 1962, President Kennedy honored Kelsey for her work. Congress also passed a law requiring drug makers to prove a drug was safe before selling it. The FDA's account of Kelsey's thalidomide review records the decision at the center of that change.
Kelsey died in 2015 at age 101.
The refusal that mattered
Kelsey faced a deadline, repeated applications, and sustained pressure from the manufacturer. She held to her finding that the safety data was inadequate.
Each 60-day refusal kept thalidomide from wider sale in the United States. For thousands of Americans, that careful review made a difference they could carry with them for life.
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