What is the thalidomide tragedy

Contergan - learning from a tragedy

Exterior view

Near the fiftieth anniversary of the thalidomide introduction, there is a dispute as to whether the two-part "A Single Tablet" produced by WDR is a documentary or a fictional film. By order of the court, the initially forbidden contribution can now be broadcast because - according to the judges - the responsible citizen knows how to distinguish very well. However, whether he can correctly assess the pharmaceutical scandal, as which the thalidomide tragedy is primarily seen, remains a question. You can find a lot in the newspaper comments accompanying the "fictional documentation" that suggests ignorance of the drug market situation at the time.

Thalidomide came on the market at the end of 1957. There was not yet our current drug law, no package insert, and the few animal experiments common at the time were only of limited use. Not only here, in the whole world, this situation has gradually changed fundamentally.

The manufacturer GrĂ¼nenthal marketed Contergan as an over the counter medicine and praised it as an innovation. Not entirely without good reason, because Contergan was the first bromine-free sleeping and sedative medication with no major side effects. Until 1961 it was a frequently used medicine, an estimated 700,000 German citizens took it every day. Since Contergan also helped against typical morning sickness in the early pregnancy phase, doctors and pharmacists specifically recommended it to pregnant women.

In terms of its side effects, thalidomide was considered particularly safe - and it was and still is today. As is well known, it is not so much the absolute effectiveness of a drug that is of interest for therapy, but its therapeutic breadth: the greater the therapeutic breadth, the safer the drug.

Thalidomide is characterized by a high therapeutic range. It was practically impossible to kill yourself with thalidomide. However, thalidomide also showed that the therapeutic breadth criterion does not cover all safety. Contergan - taken within the first three months of pregnancy - leads to severe malformations (dysmelia) or even absence (aplasias) of limbs and organs in children. Between 1957 and 1961, around 12,000 children were born worldwide with corresponding damage, an estimated 5,000 of them in Germany.

The connection between the accumulation of malformed newborns and the intake of Contergan was discovered "relatively" early by the pediatrician and human geneticist Widukind Lenz, aided by the fact that the malformations were immediately recognizable at birth.

This is completely different with diethystilbestrol (DES), another drug disaster that has largely been forgotten today. DES is a synthetic, estrogenic hormone that was used between 1940 and 1971 mainly in problematic pregnancies, i.e. against the risk of losing a child. Its value for this was recognized worldwide. It was not until 40 years after its introduction that tumors in the urogenital tract were discovered for the first time in children whose mothers had been treated with DES during pregnancy and were associated with DES. In contrast to the thalidomide tragedy, in which the deformities were recognized immediately at birth, in the DES tragedy the changes did not arise until puberty or were only recognized at this point in time.

The history of DES as well as that of the devastating thalidomide catastrophe illustrate a certain type of drug risk, which is extremely rare but can never be completely ruled out. Despite all the advances in pharmacy and completely changed control mechanisms in the development of drugs and their use in humans, this knowledge will continue to apply in the future.

Amazingly, the active ingredient thalidomide never disappeared from science, despite the thalidomide disaster, but continued to be tried and tested on animals. And in 1964, the Israeli dermatologist Jacob Sheskin, who administered Contergan from residual stocks to a leprosy patient, found that her ulcers had receded significantly the next day. As a result of this discovery, thalidomide is now mainly used in South American countries such as Colombia and Brazil against leprosy, and the substance is also being experimented with again in Germany - as a possible remedy for bone cancer and AIDS. Thalidomide is currently approved in the USA, Australia, New Zealand, Turkey and Israel, strictly observing its prohibition of use in early pregnancy.

Much has been learned from the thalidomide tragedy. Unfortunately, it also gives us an insight that is difficult to understand, but an unalterable reality: every use of a drug is a never-ending "experiment".

Prof. Dr. med. Klaus Heilmann focuses on risk research, crisis management and technology communication. In the DAZ section "Exterior View", Heilmann takes up topics from pharmacy, medicine and society from the point of view of a non-pharmacist against the background of his experiences.