Thalidomide and Teratogenic Medications: History and Lessons

On December 25, 1956, a baby was born in Germany with no arms and severely underdeveloped legs. The parents didn’t know why. Neither did doctors. That child was one of the first known victims of thalidomide, a drug sold as a harmless remedy for morning sickness and insomnia. By the time the world realized what was happening, over 10,000 babies had been born with devastating birth defects - and the number may have been twice that. This wasn’t a natural disaster. It was a failure of science, regulation, and human judgment.

How Thalidomide Became a Miracle Drug

Thalidomide was created in 1954 by a German pharmaceutical company called Chemie Grünenthal. It was designed as a sedative, but doctors quickly noticed it helped with nausea. Pregnant women took it by the millions. In Germany, the UK, Canada, Australia, and over 40 other countries, it was marketed as safe - even for use in pregnancy. No serious animal testing had been done. No long-term studies on fetal development. The drug was simply assumed to be harmless because it didn’t make people feel sick.

But here’s the truth: thalidomide didn’t cause birth defects because it was toxic. It caused them because it was too specific. In 2018, scientists finally figured out how it worked. Thalidomide binds to a protein called cereblon, which normally helps control how limbs form in a developing embryo. By disrupting that process, it literally stopped arms and legs from growing properly. A single dose during a 15-day window - between 34 and 49 days after the last menstrual period - was enough to cause irreversible damage. That’s why so many cases were missed at first. The timing was too narrow. Too precise. Too easy to overlook.

The Wake-Up Call: Australia and Germany

Two doctors, working independently, saw the pattern before anyone else. In Australia, Dr. William McBride noticed a spike in babies born with missing limbs at the Women’s Hospital in Sydney. He wrote a letter to The Lancet in June 1961, linking the spike to thalidomide. He asked for animal tests. His request was denied. He was told he was overreacting.

Halfway around the world, in Germany, Dr. Widukind Lenz was doing the same work. He tracked down every case he could find, mapped the timing of drug use to birth defects, and called Grünenthal on November 15, 1961. He told them: your drug is killing babies. Two weeks later, it was pulled from the German market. The UK followed on December 2. But in the U.S., the drug never made it to shelves - not because it was safer, but because one FDA reviewer, Frances Oldham Kelsey, refused to approve it. She demanded better data. She asked hard questions. She held the line. And because of her, thousands of American babies were spared.

The Damage Wasn’t Just Limbs

People think thalidomide only caused short arms and legs. It didn’t. It affected everything. Babies were born with no ears, no eyes, no heart valves, no esophagus. Some had no gallbladder. Others had no appendix. The UK government’s 1964 report listed over 100 different types of malformations. One in four babies died in their first year. Those who survived often needed multiple surgeries, prosthetics, and lifelong care. Many couldn’t walk, feed themselves, or hold a pen. Their lives were shaped by a pill their mothers took to sleep better.

And it wasn’t just pregnancy. Even before the birth defects were known, doctors noticed something else: people on long-term thalidomide were losing feeling in their hands and feet. Tingling. Numbness. Muscle weakness. By 1960, Grünenthal added a warning to the label: “May cause tingling in hands and feet.” But no one connected it to the babies. The neurological damage was real. The birth defects were worse. And neither was taken seriously until it was too late.

The Regulatory Revolution

After 1961, everything changed. The U.S. passed the Kefauver-Harris Amendments in 1962. For the first time, drug companies had to prove a drug was both safe and effective before it could be sold. They had to test for birth defects. They had to report side effects. They couldn’t just say, “It seems fine.”

Other countries followed. The UK created the Committee on the Safety of Medicines. Europe built new testing standards. Every drug meant for women of childbearing age now had to go through teratogenicity studies. Animal tests became mandatory. Pregnancy risk categories were introduced. And for the first time, the public started asking: “What are you testing for?”

Thalidomide didn’t just change laws. It changed how doctors think. It taught us that a drug can be safe for adults and deadly for unborn children. That a single molecule can do two things: help and harm - depending on when and how it’s used.

Thalidomide’s Second Life

Here’s the twist: thalidomide didn’t disappear. It came back.

In 1964, a doctor in Florida, Jacob Sheskin, gave it to a leprosy patient with a painful skin rash. The rash vanished. The patient slept better. The drug worked. No one knew why. But it worked.

Decades later, researchers discovered why. Thalidomide blocks the growth of new blood vessels. Tumors need blood to grow. So if you cut off the supply, the tumor starves. That’s why, in 1998, the FDA approved thalidomide for leprosy. And in 2006, it was approved for multiple myeloma - a deadly blood cancer. In clinical trials, patients on thalidomide lived longer. More than 40% were alive and cancer-free after three years, compared to 23% without it.

But the side effects didn’t go away. Up to 60% of patients had to stop taking it because of nerve damage. So today, it’s not sold over the counter. It’s not prescribed casually. It’s locked behind one of the strictest drug control systems in the world: STEPS - the System for Thalidomide Education and Prescribing Safety. Women must use two forms of birth control. They must take monthly pregnancy tests. Doctors must be trained. Pharmacies must be certified. And every pill is tracked.

Thalidomide now makes about $300 million a year. Most of it comes from cancer patients. It’s a life-saver. But it’s also a warning.

What We Still Don’t Know

Even today, we don’t fully understand why some babies are affected and others aren’t. Why do some mothers take thalidomide and have healthy children? Why do some drugs that seem harmless turn out to be dangerous only during certain weeks of pregnancy? We still don’t have a complete list of all teratogenic drugs. We’ve only tested a fraction of the 5,000+ medications on the market.

And we’re still making the same mistakes. In 2020, a drug called isotretinoin (used for acne) was found to cause severe birth defects - even when taken just before pregnancy. In 2023, a study found that certain antidepressants increased the risk of heart defects when taken in the first trimester. We know the pattern now. But do we act on it?

The Lesson

Thalidomide is not just a history lesson. It’s a living warning.

It taught us that drugs don’t always behave the same way in adults and in embryos. That “safe” doesn’t mean “harmless.” That trust without proof is dangerous. That one person asking a hard question - like Frances Kelsey - can change the course of medicine.

Today, pregnant women are told to avoid caffeine, alcohol, and certain cheeses. But what about the pills? The vitamins? The over-the-counter painkillers? We still don’t test most drugs for pregnancy safety. We assume, until we’re forced to act.

The thalidomide tragedy didn’t end in 1961. It ended when we started asking better questions. And it will end only when we stop assuming - and start testing.