The History of the Pharmaceutical Industry - Part Two: Thalidomide - The Manmade Disaster
Thalidomide was one of the biggest scandals in history, resulting in the most deaths and deformed patients following World War II. It was the pivotal culprit that changed the structure of the pharmaceutical industry during the middle of the twentieth century.
Germany, 1946. One year after the Second World War, Heinrich Mückter -a former Nazi doctor who was charged with war crimes by the Polish government- became the Head of Research at a German pharmaceutical company: the Chemie Grünenthal GmbH. From then until 1954, Mückter developed Thalidomide. At first, Thalidomide was considered a potential alternative for barbiturates -depressants of the central nervous system- since it left little to no side effects when used as a sedative. By July 1956, Grünenthal pushed Thalidomide onto German counters with no requirement of a prescription, marketing it as an anti-flu medication and in 1957, through some changes in advertising, people knew of Thalidomide as a hypnotic drug. In Germany, doctors started to prescribe it for pregnant women to prevent morning sickness.
It did not matter that the drug had never been tested on pregnant women before, at least to Grünenthal. Of all the tests that Thalidomide underwent, the only concrete conclusion was that there was no lethal dose of Thalidomide for animals. However, with this conclusion, researchers gave Thalidomide the greenlight to be used on humans. The marketing machine of Grünenthal began their job, pushing Thalidomide out into the international market.
Aggressive marketing strategies in fifty-two countries presented Thalidomide as a miracle drug safe for pregnant women. Thalidomide was an attractive deal that lured other pharmaceutical companies in other countries as well. When Grünenthal sold the license of Thalidomide in the mid-1950s, fourteen other pharmaceutical companies across the world picked it up. The product was manufactured in forty-six countries under thirty-seven different trade names. In England alone, where The Distillers Company was in charge of Thalidomide distribution, Thalidomide was known as Distaval, Tensival, Valgrain, and Asmaval.
Only in the USA did the conquest for Thalidomide come to a halt. Before that, in 1937, the USA had already suffered through a major pharmaceutical scandal. Alerts were on high against any pharma products that were presented as “a miracle”. Dr. Kelsey, an officer at the FDA at the time, was immediately suspicious of the lack of details represented in Thalidomide reports. When Dr. Kelsey’s requests for proof received no reply, she rejected the drug on American soil. Her single decision ended up saving thousands of American infants from a catastrophic fate.
Since it was not tested properly, Thalidomide’s deadly effects went undetected until it was already too late. Regular users might be affected with peripheral neuritis -a type of nerve injury which leads to numbness in the hands and feet, muscular cramps, and a lack of coordination. On fetuses, it was completely lethal. The most notable effects were phocomelia – a deformity that caused babies to be born with hands and feet absent or severely underdeveloped; internal organ damage -usually resulted in infant death, blindness, and congenital heart disease. At the same time, there was an abnormal increase in the number of miscarriages by women who used Thalidomide during pregnancy. However, this was never properly linked to Thalidomide.
With thousands of deformed babies born and probably thousands more infant deaths that went undetected, the world was on high alert. In 1959, the first wave of reports on Thalidomide’s deadly effects arrived at Grünethal. However, the German company was too enamored with profits to halt the production. At the same time, in England, Canada, and other countries where Thalidomide was sold, the same reports were rushing in. But the enormous number of trade names and distribution companies was a huge problem for a worldwide investigation. It took three years, until 1961, where the final dots were connected. All fingers pointed towards Thalidomide, the cause of a deadly pandemic that haunted an entire generation around the world.
It wasn’t until then that Grünenthal halted the production of Thalidomide, but only in Germany. The company made no move to remove the drugs from the other pharmacy’s counters. Six weeks after Grünenthal’s action -or the lack thereof- Thalidomide and its various versions were withdrawn in England. In many other countries, the drug was still available until the end of 1963.
Following the Thalidomide disaster, countries rushed to renew pharmaceutical licensing policies. Each country had its twists and turns with its laws. For example, the Yellow Card Scheme was introduced in England in 1964, which allowed doctors and pharmacists to report a pharma product immediately once they detected any alarming effects. A few years later, in 1968, England also passed the Medicines Act that differentiates prescription drugs, drugs for general sale, and drugs available in pharmacies. Even the U.S. -where Thalidomide was not distributed- updated their policies after the disaster with the Kefauver-Harris Drug Amendments Act, which lengthened the drug approval process to eight or twelve years, included sufficient animal testing, and tightly regulated human clinical trials.
The story of Thalidomide, however, did not stop there. England and Canada set up trusts to compensate Thalidomide survivors. In Germany, the perpetrators walked free after their trials in 1968, and research about Thalidomide continued. In 1964, not long after it was withdrawn from the pharmacy’s counters, Thalidomide was discovered to have positive effects against leprosy. However, due to its deadly side effects, in 1967, WHO oversaw Thalidomide trials for leprosy. Thalidomide was also reported to have positive effects against HIV and Multiple Myeloma, a type of bone cancer. As a result, its usage continued, but under heavy regulation. Researchers are also working on developing similar drugs, like Lenalidomide (Revlimid) and Pomalidomide (Pomalyst), of course, without deadly effects.
However, in less developed countries, the situation regarding Thalidomide does not look good. In South America, Thalidomide can still be bought online, without any precaution regarding its negative effects. A report in 2015 saw a total of 5,889,210 Thalidomide tablets distributed in Brazil, where it has been locally manufactured since the 1980s. In contrast to England, the U.S., or Canada, where patients are sufficiently informed of Thalidomide’s effects, the same could not be said for many other developing countries. This is alarming, considering the side effects that made Thalidomide a manmade disaster in the first place. Activists in these countries, who are well aware of its effects -both good and bad-are campaigning for stricter drug regulation in their homelands and for developed countries to include or share with them the progress on Thalidomide research. All of these efforts share the same goal: to prevent a global catastrophe such as Thalidomide from repeating itself.
In 1956, Thalidomide was sold without prescription in Germany. Thalidomide then appeared in 46 countries under various trade names.
In 1959, the first wave of reports about Thalidomide’s deadly effects on babies started to arrive. However, only starting from 1961, many countries took legal actions against Thalidomide. Its production was finally stopped.
Countries started to update their pharma policies after the Thalidomide scandal.
Research about Thalidomide continues. It is reported to have positive effects against leprosy, HIV, and multiple myeloma.
There is a stark contrast in the regulation of Thalidomide in developed and developing countries.