The first wake-up call regarding thalidomide was in 1956, before it was widely distributed over the counter. One of Chemie Grunenthal's employees decided that his pregnant wife needed to be treated for morning sickness and ailments with the new drug Contergan (the trade name for the first version of thalidomide). The daughter was born without ears!
Then, of course, no one identified a causal relationship, and a year later the drug went into series. It is noteworthy that initially the drug was considered as an anticonvulsant, but tests showed not the highest efficacy of thalidomide in this direction. Therefore, it was decided to use its "side" property to calm patients and give deep sleep. In the pharmaceutical market of that time, Contergan was almost the most effective drug, attracting rave reviews from both patients and their doctors. Pregnant women have successfully used the novelty in the fight against morning sickness, insomnia and anxiety.
It is worth mentioning that no one conducted preliminary tests of the drug on pregnant animals, and even more so on women "in position". And thalidomide was conquering new markets every year: at the peak of its career, it was sold in more than forty countries around the world. Except for the USA. But more on that later. In particular, it was only in the UK that thalidomide could be found on pharmacy shelves under the brand names Distaval (Forte), Maval, Tensival, Valgis or Valgraine. Four years after the release of thalidomide drugs on the market, German doctor Hans-Rudolf Wiedemann pointed to an abnormally high percentage of congenital malformations and directly linked this phenomenon to a side effect of the sedative. Prior to this, many doctors from Germany pointed to the increased incidence of stillbirth and deformity, but they attributed this to atmospheric nuclear tests in the United States. In 1958, they even sent relevant inquiries to the defense department.
The action of the teratogen was terrible: the fetus inside the mother lost its eyes, ears, internal organs and was often born already dead. The most widespread was phocomelia, or seal limb syndrome, when a newborn was either completely deprived of limbs, or they were underdeveloped. At the same time, thalidomide did its dirty work not only in the female body, but also disrupted the processes of sperm formation, condemning future fathers to inferior offspring.
There is an interesting person in this story - Australian gynecologist William McBride. In December 1961, he published an article in the authoritative magazine The Lancet on the teratogenic effects of the sedative Chemie Grunenthal. It was from him and from the mentioned Hans-Rudolf Wiedemann that the world community learned about the terrible drug. McBride immediately became famous and even received the prestigious French medal and cash prize from L'Institut de la Vie. But fame is very changeable - after a while the thalidomide scandal subsided, and McBride was forgotten.
The gynecologist later tried to draw attention to his person by the alleged connection between deformities and the use of certain antidepressants, but nothing could be proved. And in 1981, he suddenly accused the drug Debendox of a teratogenic effect similar to thalidomide, fabricated test trials and published it all. Only in 1993, doctors and pharmacists figured out the fraud and deprived the former celebrity of the right to practice medicine until 1998.
But back to thalidomide. He was removed from the market in December 1961, immediately after the publication in the authoritative medical journal The Lancet, but the picture of his atrocity was amazing. About 40,000 people were affected by peripheral neuritis, the most harmless side effect of thalidomide. More than 10 thousand children were born (data differ in the sources) with severe developmental disorders, of which more than half survived. Now many of them have been able to sue Chemie Grunenthal for compensation and life support. The German government also supports people with disabilities from birth with monthly benefits, which are barely enough for some. For example, in 2008, several victims of thalidomide demanded a threefold increase in disability pensions at once and went on an indefinite hunger strike.
Francis Kesley - the savior of the United States
Why is thalidomide such a potent teratogen? The mechanism of its action was discovered literally nine years ago, and before that they only knew that a molecule of a substance can exist in two optical isomers (this is a course in the school chemistry curriculum). One form heals, and the other, accordingly, cripples. At the same time, even a simple purification of the drug from teratogenic isomers will not help: our body will independently make a particularly dangerous molecule from a useful form. After revealing publications about the Kontergan disaster, many medical centers began testing thalidomide-based drugs in pregnant rodents. And it turned out that there is no teratogenic effect in mice even at prohibitive dosages. That is, even if Chemie Grunenthal had conducted preliminary Contergan tests on laboratory animals, the dangerous drug would have passed them successfully. Even repeated studies on pregnant monkeys did not reveal any contraindications for introducing the drug to world markets.
However, thalidomide still could not convince one pharmacist of its own safety. An employee of the US Food and Drug Administration (FDA), Francis Kesley, even before the start of the Contergan scandal, expressed great doubts about the harmlessness of the drug for pregnant women. Whether it was indicated by mild side effects or it was Francis's professional instinct, we cannot say for sure, but the drug was not allowed on the US market. A small number of free games for testing does not count. And when the whole world learned of the thalidomide disaster, Kesley became the country's national hero. It turned out that the researcher made her decision under pressure from the Richardson-Merrell company (marketing division of Chemie Grunenthal), which is in every possible way imposing a new drug on the FDA. If Kesley had not sent the drugs for additional research in 1960 (which, as is clear, would have gone nowhere), time would have been lost and thalidomide would have ended up in pharmacies. But while the cycle of tests on pregnant animals was being launched, while the results were being evaluated, it was December 1961, and all further work turned out to be superfluous. John F. Kennedy personally presented Francis Kesley with the state award for the professionalism that saved thousands of American lives.
A lawsuit was launched against Chemie Grunenthal, but the real culprits were never identified. It was rumored that employees destroyed a lot of the drug test results in time. Be that as it may, the company paid 100 million marks to the Thalidomide Victims Fund, which still pays life pensions to people with disabilities around the world.
The Kontergan disaster forced stricter drug controls and dramatically increased pharmaceutical companies' spending on new drug development. The most interesting thing is that doctors around the world still prescribe thalidomide-based drugs to their patients. Of course, not for expectant mothers and not as a sleeping pill, but as a powerful anti-cancer agent. There is research that the infamous thalidomide can almost be treated for AIDS.