One Doctor’s Doubts: How America Avoided a Thalidomide Disaster

In the late 1950s, thalidomide became one of the world’s most widely used sedatives. It was sold in numerous countries as a sleep aid and calming medication, and later as a treatment for morning sickness during pregnancy. The drug appeared under different brand names. In West Germany, it was known as Contergan, while in the United States, William S. Merrell, part of the Richardson-Merrell group, sought approval to market it as Kevadon.

At the time, the modern system of drug review that we know today did not yet exist. There were no requirements comparable to today’s phased clinical trials, detailed informed consent procedures, comprehensive safety files, proof of effectiveness, close monitoring of side effects, and regulated reporting to authorities.

For generations, traditional medicine had relied largely on experience, authority, observation, and accepted practices. Even in the early years of modern medicine, systematic scientific evidence was not always required. A drug could gain acceptance based on doctors’ recommendations, favorable letters, informal observations, or a manufacturer’s confidence in its product.

How Drug Safety Regulation Developed in the United States

American drug regulation developed gradually.

In 1906, the Pure Food and Drugs Act was enacted, focusing primarily on adulterated products, misleading labels, and potentially harmful substances. However, the law still did not establish what we would recognize today as comprehensive scientific approval before a drug could reach the market.

Then came the Elixir Sulfanilamide disaster of 1937. A liquid medication containing a toxic solvent was distributed without adequate safety testing, resulting in the deaths of more than 100 people.

In response, Congress passed the Federal Food, Drug, and Cosmetic Act in 1938. The law required manufacturers to submit an application for a new drug to the FDA and provide evidence of its safety before marketing it.

Yet crucial elements were still missing. Manufacturers were not yet required to systematically prove that a drug was effective, and oversight of clinical trials and documentation of patient outcomes remained far less rigorous than it is today.

That was the regulatory environment in which Frances Oldham Kelsey arrived at the FDA.

In 1960, Kelsey joined the agency in Washington, D.C. She was new to the FDA and one of a relatively small number of medical officers responsible for reviewing applications for new drugs.

On September 8 of that year, an application for Kevadon, the proposed American version of thalidomide, landed on her desk.

On the surface, it appeared to be a straightforward application. Thalidomide was already being sold outside the United States. It was promoted as exceptionally safe and had achieved considerable commercial success. The company expected the approval process to move quickly.

But when Kelsey examined the material, she did not find the evidence she wanted to see.

There were recommendations, letters, broad claims of safety, and reports that relied heavily on doctors’ impressions. What she did not find were adequate studies that could reassure a cautious medical reviewer.

Convincing toxicity data were lacking. Adequate studies in pregnant animals were lacking. There was no satisfactory answer to a crucial question: What could happen to a developing fetus if a pregnant woman took the drug?

Most importantly, there was insufficient evidence that thalidomide was safe for one of the very groups for whom it was being promoted: pregnant women suffering from morning sickness.

Frances Kelsey Refused to Approve Thalidomide Without Proof

The pharmaceutical company did not consider these concerns sufficient reason to hold up approval. After all, thalidomide was already being widely used in other countries. Doctors were prescribing it, and in some places it was being sold in large quantities.

At the time, widespread use without an immediate wave of obvious poisoning could itself create an impression of safety.

Kelsey was not satisfied with impressions. She wanted evidence.

Under the system then in place, she had 60 days to object to the application before it could become effective. As each review period approached its end, she requested additional information from the company, restarting the review period.

The company supplied more material, but Kelsey’s questions remained unanswered.

Representatives came to Washington, met with officials, complained about the delays, and repeatedly pushed for the application to move forward. They also attempted to take the matter above Kelsey, but her supervisors supported her position.

Meanwhile, thalidomide had already entered parts of American medicine despite not being approved for commercial sale.

At the time, pharmaceutical companies were permitted to distribute samples of drugs classified as experimental to doctors. Under this framework, Merrell distributed more than two million thalidomide tablets to doctors and patients across the United States.

Recordkeeping and oversight were far less rigorous than they would become in later years, and some of those who received the drug were pregnant women.

Thalidomide was not sitting on American pharmacy shelves as an approved medication, but it was already circulating.

A Tragedy Was Unfolding in Europe

At the same time, doctors in Europe and Australia were beginning to notice a devastating pattern.

Hospitals, maternity wards, and pediatric clinics were seeing babies born with severe abnormalities affecting their limbs and other parts of the body. Physicians began investigating whether there could be a connection to thalidomide use during pregnancy.

By November 1961, evidence linking thalidomide to severe birth defects had mounted, and the drug began to be withdrawn from markets in various countries.

In March 1962, Merrell withdrew its application to market thalidomide in the United States.

That July, journalist Morton Mintz brought Frances Kelsey’s story to national attention in The Washington Post. Americans learned that for months, a relatively new FDA medical officer had stood firm against pressure from a major pharmaceutical company and the prevailing assumptions surrounding a popular drug.

Her demand was simple: Show me the evidence.

Her refusal to approve thalidomide prevented the drug from being widely marketed in the United States and spared the country from experiencing the tragedy on the scale seen elsewhere.

The global toll was devastating. More than 10,000 children are commonly estimated to have been born affected by thalidomide worldwide, in addition to pregnancies that ended in miscarriage or stillbirth.

The United States did not escape entirely. Because thalidomide had been distributed through the experimental drug program, some American babies were affected. But because the drug never received approval for commercial sale, the scale of the tragedy in the United States was dramatically smaller.

The Case That Helped Transform Drug Regulation

In August 1962, President John F. Kennedy presented Frances Kelsey with the President’s Award for Distinguished Federal Civilian Service, one of the highest honors given to a federal employee.

Just two months later, on October 10, 1962, Kennedy signed the Kefauver-Harris Amendments into law.

The legislation fundamentally changed the way drugs were regulated in the United States.

It was no longer enough for pharmaceutical manufacturers simply to demonstrate that a drug was safe. They also had to provide evidence that it was effective.

Clinical trials came under stricter oversight. Informed consent for research participants became a requirement. Manufacturers had to provide the FDA with more complete information about clinical investigations and the distribution of experimental drugs. Preclinical research, including animal studies, became a more important part of establishing a drug’s safety before testing and widespread use in humans.

The thalidomide disaster became one of the defining events in the history of modern drug regulation. And at the center of the American chapter of that story was a physician who refused to accept popularity, commercial success, or reassurance as substitutes for evidence.

Frances Kelsey simply kept asking for proof.