Thalidomide was never approved in the US. In fact, as noted in Regulating New Drugs: The application was delayed for reasons having nothing to do with potential risks and was moving towards approval when the company itself reported the horrible side effects. It took four months for the FDA to realize that people were at risk and in fact Helen Taussig, a cardiologist at Johns Hopkins University had been sounding the alarm about thalidomide for years. The FDA finally acted after John F. Kennedy insisted on it.
The current FDA approach -- a product of the 1962 amendments to the Food and Drug Cosmetic Act -- and dependency on the randomized controlled trial is a legacy of the political reaction to a problem. Efforts to increase regulatory flexibility at the FDA are opposed, the critics always invoke "another thalidomide."
Most people stop the story there. It’s an open and shut case, they say, thalidomide was a horribly dangerous and deforming drug allowed to get onto and stay on the market due to grossly inadequate safety testing and monitoring and the callous actions of companies interested in profits over patients. This, they believe, is why we cannot be too careful about any drug that might be risky. But the tale of thalidomide doesn’t end with its withdrawal – and millions have lived better, longer lives because of it.
In the mid-1960s, thalidomide came back to life. As many discoveries in medicine are, it was due to chance. Dr. Jacob Sheskin was the head of the Jerusalem Hospital for Hansen’s Disease (or what most people call leprosy) when one day he was sent a patient with extremely advanced erythema nodosum leprosum or ENL, a very painful and debilitating side effect of leprosy that causes boils, joint pain, inflammation, and intense pain. Patients waste away, unable to eat or sleep and dependent on morphine and sedatives to control their agony. About 60 percent of people with advanced leprosy get ENL.
The patient who arrived at the Jerusalem Hospital in 1964 was close to death and had received almost no benefit from any sedative available. While trying to figure out whether there was anything that could be done for him, Dr. Sheskin stumbled upon a small stash of thalidomide, now no longer sold. But remembering the use of the drug in mental patients who similarly responded to no other sedative, the doctor decided it was worth a try. It worked. Spectacularly. Not only was the patient finally able to sleep but his ENL began to improve radically. The same thing happened with other patients with ENL. Sheskin then embarked on a series of controlled clinical trials in Venezuela, where thalidomide could still be purchased, and confirmed his findings. Soon the drug was promoted by the World Health Organizations for use in ENL patients and because of it the vast majority of facilities to treat leprosy have been able to be closed. Even the US allowed highly controlled use of thalidomide for ENL beginning in 1975.
In the 1980s, thalidomide found another use: AIDS patients. Like those with ENL (and tuberculosis patients, who had also been helped by thalidomide), people with AIDS suffered from severe wasting. They also got sores in the mouth and esophagus called aphthous ulcers, caused like the wasting by caused by a chemical called TNF-ɑ (tumor necrosis factor alpha), and a rare cancer called Karposi’s sarcoma. The drug worked well, but it was hard to get a hold of. Many AIDS patients obtained it from abroad, mostly via Mexico, through buyers’ clubs but these channels were dubious and the quality and purity unsure. Researchers into the uses of thalidomide had likewise found that it was difficult to obtain and so one, Dr. Gilla Kaplan, finally managed to convince a small pharmaceutical firm called Celgene to apply to the FDA for approval to produce thalidomide.
While the process to get the drug through the FDA was ongoing, research into its potential use as an anti-cancer drug was in process by leading cancer researchers Dr. Robert D’Amato and Dr. Judah Folkman. They were working on angiogenesis, the growth of blood vessels, and hoped that finding a way to inhibit it would allow the development of drugs to fight cancer, as well as several other diseases. It was thalidomide’s anti-angiogenic effects that caused the birth defects but also made it a perfect candidate from D’Amato and Folkman’s research. Subsequent study found that the drug is also very effective against multiple myeloma, a difficult to treat cancer that attacks the plasma cells in the blood. In July 1998, after a long and spirited debate and heartfelt stories from both victims of thalidomide and those helped by it, the Celgene drug --Thalimid was approved by the FDA under the condition that patients are carefully monitored and extensive safeguards enacted to prevent pregnant women from taking thalidomide. Once in use, the benefits of thalidomide analogues in resetting the immune system to reduce tumor growth, became apparent. It launched a whole new field of treatments and the introduction of several new medicines. New uses, especially for rare autoimmune conditions, are still being discovered, even as old ones are sometimes superceded. In its current usages, the drug has benefited millions of patients around the world.
The thalidomide story is a many told tale: Each year millions of people suffer because fearmongers invoke the handful of side effects or deaths from the use of a medicine. Indeed, the number of adverse events from drugs as a percentage of all prescriptions did not change after the 1962 amendments. The number of withdrawals as a percentage of all medicines has remained the same. FDA regulation is a very expensive tranquilizer to calm the nerves of the public. We have more expensive medicines, fewer new medicines for specific groups of patients and less competition.
Enshrining Francis Kelsey as a hero is a ritual detached from the truth. It is an exercise designed to reinforce the precautionary approach that has slowed down the development and use of medical innovations for over 50 years.