NRP Spring 2023. Jack Diers: Thalidomide: The tragedy that transformed the pharmaceutical industry

In the late 1950s, thalidomide was the newest ‘wonder drug’ and was widely used in Europe as an anti-emetic and sedative to treat morning sickness. It was hailed for its safety- evidenced by the fact that no amount of thalidomide could kill a rat. As a result, thalidomide quickly rose to fame around the world, outcompeting aspirin in many markets. As thalidomide grew in popularity, so too did reports of potential thalidomide-related birth defects, most commonly limb stunting or absence (phocomelia), malformation of hands/digits, and eye/ear damage. Thalidomide’s manufacturer- Chemie Grünenthal- denied any notion that thalidomide- the miracle drug that couldn’t possibly harm a rat- caused any birth defects (note: it’s now known that thalidomide does not act the same in rodents as it does in primates). In 1961, Dr. Widukind Lenz in Germany and Dr. William McBride in Australia independently demonstrated a causal link between thalidomide and birth defects. Subsequently, Thalidomide was classified as a teratogen (an agent that causes abnormalities or birth defects in a fetus) and was banned in 1961, less than five years after coming to the market in 1956. While only available for a short time, Thalidomide was attributed to birth defects in over 10,000 babies, around half of which died shortly after birth.

The story of thalidomide is a tragedy, but it easily could’ve been prevented. One heroic figure in the thalidomide narrative is Dr. Frances Kelsey, a scientist at the FDA during the rise of thalidomide. Her first case at the FDA was thalidomide- which was given to her because it seemed like an open-and-shut case. However, Dr. Kelsey was skeptical of thalidomide and its effect on pregnant women, even before the link between thalidomide and births defects was discovered. While thalidomide appeared safe, there was no testing done on pregnant animals. Dr. Kelsey’s previous work with the placental barrier had shown that drugs ingested by the mother could affect the fetus- something many scientists thought was not possible in the late 1950s. Dr. Kelsey rejected thalidomide. As a result, the US largely avoided the thalidomide tragedy, and Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service by President John F. Kennedy.

The tragedy of thalidomide revolutionized the pharmaceutical industry so that such a tragedy could never happen again. In large part because of the efforts of Dr. Kelsey, federal drug regulations grew much stricter, mirroring the intense regulations today. Prior to the thalidomide scandal, drugs could be approved based solely on animal testing. Additionally, in the US, federally regulated clinical trials became mandated, and drug manufacturers were now required to demonstrate a drug’s efficacy and any potential side effects (Kefauver Harris Amendment). Even if trial results were promising, the new regulations gave the FDA ultimate say in if a drug comes to market, whether it requires a prescription, and how it is allowed to be advertised.

The story of thalidomide speaks to how the pharmaceutical industry works. Drugs are rarely ever used to treat one condition and often work much better at treating a disease they weren’t created for. Thalidomide is one such case. After it was banned in 1961, thalidomide survivors hoped to never see thalidomide again. However, in 1964, thalidomide was shown to prevent blood vessel growth. Thalidomide’s anti-angiogenic effects- which are responsible for disrupting limb growth in utero- made it a promising treatment for various other conditions from leprosy to cancer. Thalidomide re-emerged as a treatment for leprosy all over Africa, leading to its eventual approval in the US in 1998, when fears of its destruction finally dissipated. Thalidomide is now the primary treatment for multiple myeloma and can be used treat other diseases like tuberculosis, multiple sclerosis, and HIV. Women on thalidomide are required to use two forms of birth control and take regular pregnancy tests and men are urged to wear protection during sex- all to prevent children with birth defects or “thalidomide syndrome”.

The legacy of thalidomide is twofold: a painful history of suffering and loss, and a transformative influence on drug regulations and patient safety. The resurgence of thalidomide as a treatment for various conditions is a testament to the adaptability of medicine. Yet, the lessons learned from its initial failure continue to linger on, emphasizing the need for vigilance, empathy, and integrity in the pursuit of medical advancement.