The creation and early use of thalidomide is one of the most famous, tragic disasters in drug development history. It was prescribed to pregnant people for morning sickness in the late 1950s and early 1960s, but it was later discovered that taking thalidomide while pregnant caused serious birth defects. Once the danger was discovered, thalidomide was pulled from shelves, and it’s a landmark story in the stakes of drug safety screenings, and one of the most famous international scandals in modern medicine.
So it may come as a shock to hear that we’re still using thalidomide - it’s good for more than just treating nausea. Part of the reason we’ve resurrected the drug has to do with the very same drug testing procedures that it inspired. Thalidomide is incredibly dangerous during pregnancy, causing at least 10,000 children to be born with severe congenital health problems, from deformed arms to issues with their organs like heart or kidneys. Up to 40% of these were fatal, and that doesn’t even include countless more thalidomide-affected pregnancies that ended in miscarriages.
Once thalidomide’s connection with birth defects were discovered, most countries banned the drug entirely in 1961 and 1962. This tragedy inspired us to step up drug safety standards, and all drugs must now be tested for harm to fetuses in at least two types of animals.
However, this high level of safety comes with a high price tag, which is why pharmaceutical companies and researchers are so interested in using old drugs for new tricks. As it happens, researchers knew about thalidomide’s potential for treating other conditions, almost right away. It was approved by the FDA to treat Hansen’s Disease, and is still used today to treat complications of that disease, as well as HIV, lupus, Crohn’s disease, and more.
The reasons thalidomide works in these cases may be linked to why it causes those awful birth defects. Thalidomide binds to a protein called cereblon, which plays a vital role in the developing limbs and organs as a fetus grows, but the interaction between thalidomide and this protein also reduces how many inflammatory molecules get produced, in particular a molecule called TNF-alpha.
In the 1990s, interest in thalidomide started to really ramp up, as researchers thought maybe it could even help treat cancer. TNF-alpha can both help and hurt the body’s fight against cancer, and thalidomide has another trick up its sleeve called anti-angiogenesis, which blocks blood vessels from growing. This can help slow down tumors. The story of thalidomide is a lesson in the importance of drug safety testing. Despite potential side effects, such as nerve damage, trials investigating cancer treatment with thalidomide were overall successful, showing it can work against cancers of the esophagus, kidneys, and pancreas, among others. In 2006, the FDA approved it to treat multiple myeloma.
In order to ensure safety, the FDA controls thalidomide under a Risk Evaluation and Mitigation Strategy (REMS) program. This means they verify everyone who gets the drug isn’t pregnant already, knows the risks associated, and uses multiple methods of birth control. They also evaluate the risk of medication being mixed up between people in a household, or even being shared inadvertently through intercourse or blood and sperm donations.
The program seems to have worked well, as 98% of patients knew the correct answers when quizzed about the risk of birth defects. A 2007 study notes that zero new cases of birth defects from thalidomide have been reported in the United States since the drug was approved in 1998!
The story of thalidomide illustrates that while a certain medication might have nasty side effects, it might still have a crucial role to play in how we treat other illnesses. Repurposing something we’ve already studied can be an efficient way to develop new treatments.
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