Thalidomide: A forgotten history

The COVID-19 vaccine is coming… eventually. There is a push by Trump to get it out to the general public prior to the election no matter the cost… gee I wonder why? However, we have testing standards in place for a very good reason and while it can be medically necessary to provide promising medicine in a few select cases, this is not one of them. A history lesson is in order and like all history, we may be doomed to repeat it if we don’t learn from it.

Thalidomide, I had never heard of it until my undergrad organic chemistry course. This is a story of tragedy, war, drug company profit, the FDA, and a whole lot of bad luck. It’s also a warning of the unintended consequences that can come from inadequate testing.

As you might imagine, after world war 2 there was a lot of people dealing with trauma and the fog that comes from spending what feels like an eternity fighting a war only to have it abruptly end. The demand in Europe for tranquilizers and medications to help people sleep was huge and drug companies were rushing to fill the vacuum with options. Even in America, it was estimated that one in seven people were using medications to help them sleep. If war is hell, then the post war years is purgatory.

Thalidomide was the first and only (at the time) medication non-barbiturate sedative known. It was presumed incredibly safe at the time and for that reason it’s appeal was huge. Sadly,  tragedy followed its release and helped catalyze the beginnings of the rigorous drug approval and monitoring systems in place at the USFDA. Protocols that were not in place at the time.

This was a time when drug testing was done by the company without any real oversight and no governing body. Thus Thalidomide entered the German market in 1957 as an over-the-counter remedy, based on the maker’s safety claims. They advertised their product as “completely safe” for everyone, including mother and child, “even during pregnancy,” as its developers “could not find a dose high enough to kill a rat.” Sales skyrocketed with it’s release in 1960. Thalidomide was marketed in 46 countries, with sales nearly matching those of aspirin.

Around this same time, an obstetrician from Australia named Dr. William McBride discovered that the drug also alleviated morning sickness. So he started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend. I should mention, this isn’t as strange as it sounds. Prescribing drugs for off-label purposes (purposes other than those for which the drug was approved) is still a common practice in many countries today, including here in the U.S. In many cases, these off-label prescriptions can be very effective.

It was believed (even though there was evidence to the contrary at the time) that no drug could cross the placenta, so no harm would come to children. So the makers never even checked how it affected pregnancy. However, in 1961, McBride began to associate this so-called harmless compound with severe birth defects in the babies he delivered. The drug interfered with the babies’ normal development, causing many of them to be born with (warning: the link is somewhat graphic) phocomelia, resulting in shortened, absent, or flipper-like limbs.

A German newspaper then reported 161 babies were adversely affected by thalidomide. This FINALLY led the makers of the drug (who had ignored reports of the birth defects associated with the it) to finally stop distribution within Germany. Other countries followed suit and, by March of 1962, the drug was banned in most countries where it was previously sold. One country where this drug wasn’t even being sold yet (notice I said being sold)? The US, this was thanks to the actions of the Food and Drug Administration (FDA).

Frances Kelsey, the FDA inspector at the time prevented the drug’s approval within the United States. This was despite pressure from the pharmaceutical company and her FDA supervisors! She felt the application for thalidomide contained incomplete and insufficient data on its safety and effectiveness. Among her concerns was the lack of data indicating whether the drug could cross the placenta.

This is where I point out again that even if there was studies to show this, the validity of them may have come into question because there was little oversight. At the time, clinical trials did not even require FDA approval! Sadly, the “clinical trials” of thalidomide in the US involved distributing more than two and a half million tablets of thalidomide to approximately 20,000 patients across the nation—about 3,760 women of childbearing age, at least 207 of whom were pregnant. More than one thousand physicians participated in these trials, but few bothered to track their patients after dispensing the drug.

The tragedy surrounding thalidomide and Kelsey’s refusal to approve the drug motivated profound changes in the FDA. By passing the Kefauver-Harris Drug Amendments Act in 1962, legislators tightened restrictions surrounding the surveillance and approval process for drugs to be sold in the US. It required that manufacturers prove they are both safe and effective before they are marketed. Now, drug approval can take between eight and twelve years, involving animal testing and tightly regulated human clinical trials.

While there are reports that claim this drug was never available in the US, this is not true, it just wasn’t widely marketed as it was going through “clinical trials.” So while tragedy here in the US wasn’t completely prevented, it could have ended up being a whole lot worse.

The moral of the story is a very simple one. Humans are complex creatures and the long-term consequences of a medication, or in this case a vaccine, can be deadly. While it can be frustrating that a drug that appears to be promising is kept out of reach of the people who desperately need the relief, keep in mind that there are good reasons why this system is in place. It’s not only the law, it’s a moral obligation for researchers, doctors, and drug makers, to make sure that these treatments will help and not harm.