Daily MOS: Thalidomide and Teratogenesis

Regulations are written in blood, the saying goes. Often when you find rules that feel like common sense now, scratch the surface gently, and inevitably, immense amounts of human suffering was the triggering event.

In an era when parents knew that castor oil cured more than just a child’s will to live and people still weren’t so sure about the suggestion of a link between lung cancer and smoking, thalidomide was marketed as a safe and effective morning sickness remedy.

Today’s Moment of Science… the drug that couldn’t kill a rat.

First synthesized in 1953, thalidomide was initially researched as an anticonvulsant. That failed, but somehow it worked for goddamn everything else. Cough? Headache? Insomnia? Take some thalidomide, it’s the CBD of its time. It was a wonder drug, first being prescribed as a sleeping pill with widespread evidence of safety. In an era when people were popping quaaludes like m&ms, this promised to be a drug that didn’t get you high and let you sleep through whatever was so stressful about the 1950s. According to every single test needed to put it onto the market for that era, it was patently non-toxic for a healthy adult.

As it had been for every other ailment, it seemed a godsend for expectant mothers suffering from morning sickness. Doctors were thrilled to dole out this safe drug.

Months later, after desperate mothers tried to stay healthy through their pregnancies, their children were born with severe limb deformities.

It took warnings from multiple countries and doctors before manufacturers pulled it from shelves, but curiously not the US. Why?

It never made it onto the shelves here to begin with.

Dr. Frances Oldham Kelsey spent a lifetime forging a safer pharmaceutical market. While in graduate school, she performed research on the drug Elixir Sulfanilamide to find out why it had been linked to over 100 deaths. Her findings led to creation of The Federal Food, Drug, and Cosmetic Act of 1938, ensuring that drugs must be proven safe before approval.

After earning her MD, she went on to work as one of seven drug reviewers at the FDA. One of her earliest tasks was reviewing thalidomide, including explicitly approving it for morning sickness relief. She balked due to what she saw as a lack of sufficient safety and efficacy data. They sent out over two and a half million tablets of thalidomide for their trial, 20,000 patients received the tablets, and follow-up was inconsistent at best.

Only 207 of the patients in their drug trial were pregnant.

Within a year of her initial refusal to approve it, there were widespread reports of mothers on the medication birthing children with limbs that were absent or truncated. The thought hadn’t even floated that this drug, laughably non-toxic, could have such profound effects on a fetus.

Dr. Kelsey was lauded as a hero. The Kefauver–Harris Amendment was added to the Federal Food, Drug, and Cosmetic Act. The amendment added that they had to ensure both safety and efficacy. Since then, clinical trials have standardized. Toxicological effects on non-target systems have to be checked. Teratogenicity testing is a part of all major drug testing.

Thalidomide, as it turns out, is still fairly non-toxic if you’re not pregnant. Peripheral neuropathy can be a side effect with long term use, but it’s approved as long as you’re not currently incubating anything. It’s currently used to treat leprosy and multiple myeloma.

This has been your daily Moment of Science, and a reminder that no, things were not better in the good old days.

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