Marketed in the late 1950s by the German laboratory Chemie Grünenthal, thalidomide is a substance present in sedatives which was delivered to pregnant women and caused malformations in their babies. It is now used in France for other indications.
Between the end of 1950s and early 1960s, there thalidomidean active substance present in medications, is issued to pregnant women as sedatives/tranquilizers to treat headaches, nausea and colds during pregnancy. Considered as “a wonder drug” well tolerated, thalidomide was found at the heart of a pharmaceutical scandal d‘global scope when it was realized that it had caused birth defects in thousands of newborn babiesresponsible for many deaths.
When and which laboratory developed thalidomide?
Thalidomide is synthesized in 1954 in Germany of the West by the German firm Chemie Grünenthal. It is put on the market in 1956 in Germany as a hypnotic/sleeping pillin 1958 in the United Kingdom and Japan, in 1959 in Norway and Canada, then in fifty countries around the world under forty different names (Distaval®, Grippex®, Kevadon®, Softénon®, Talimol®, Kevadon®, Sedimide®, Quietoplex®…). The best known is the Contergan®. It should be noted that thalidomide was never issued in the United States because the Food and Drug Administration (FDA) had refused to approve it, for lack of sufficient research. Neither in France because the health authorities were (luckily) very slow to authorize its marketing French.
What are the indications for thalidomide when it is marketed?
Thalidomide is a molecule that has sedative, hypnotic effects And anti-inflammatoriesissued when it is placed on the market for pregnant women to relieve morning sickness, headache, cough and cold symptoms during pregnancy. When it was marketed at the end of the 1950s, it appeared as a “miracle drug”: a alternative to barbiturates used as sedatives (the only tranquilizers available at the time but which, in the event of an overdose, can be fatal) which does not appear to be toxic for pregnant women nor responsible for side effects. Thousands of samples are then distributed to doctors who are encouraged to prescribe thalidomide to pregnant women, in the belief that the drug is safe.
Summary and key dates of the thalidomide scandal
► In 1956: thalidomide is put on the market, over-the-counter (without prescription), for the first time in the form of a sleeping pill marketed under the name of Contergan® (or under other names depending on the country of sale)
► In December 1956: A first baby born with birth defects. During the pregnancy, the baby’s mother had taken sleeping pills (in self-medication), which her husband, then employed at the Grünenthal laboratories, had brought back from the research department. At that time, the link was not yet made between taking this new drug and congenital malformations.
► From the late 1950s to the early 1960s: nearly 12,000 children are born in Europe with severe malformations legs, arms, hands, ears and internal organs as well as peripheral neuropathies (functional disorders of one or more peripheral nerves). Most of the mothers were treated with thalidomide during pregnancy, but the doctors rather incriminate different factors (the radioactivityatomic tests, detergents, viruses, etc.).
► In August 1961, the German weekly Der Spiegel publishes an article on these malformations and their possible link with thalidomide. This leads to a drop in sales of Contergan® (turnover divided by 50). At the same time, cases of congenital malformations continue to increase.
► In November 1961: THE Dr Widukind Lenza physician from Hamburgpresents at a congress of pediatrics in Düsseldorf (Germany), the results of his research, which establish a real link between taking thalidomide and malformations. There followed a press release from the authorities of the region deciding to withdraw the authorization for sale of Contergan® because of teratogenic risks. That same month, the Chemie Gruewenthal laboratory sent a letter to thousands of doctors warning them not to prescribe thalidomide to women who were pregnant or likely to become pregnant.
► Between December 1961 and January 1962, a few weeks after the Pediatrics Congress: the sale of thalidomide is prohibited first in Germany, the United Kingdom and then in most countries of the world. But it’s too late: thousands of babies are born with major malformations around the world. A few countries continued to issue thalidomide until the end of 1963.
► In 1963: several trials followed. The first trials begin in Japan and in Hamburg, Germany. The indictments against the firm Chemie Grünenthal state manslaughter, assault and willful negligence. The majority of the relatives of the victims are demanding an agreement with Grünenthal and want to stop there. Another part of the parents decide to continue the legal proceedings.
► From 1968 to 1969: a second trial is therefore taking place in Germany. This is the longest trial in the Federal Republic of Germany after the Nuremberg trial. There are 400 plaintiffs, defended by 7 lawyers, who oppose the Grünenthal Company, which is defended by 20 lawyers. “What the public did not know was that Grünenthal had no reliable evidence to support his claims that the drug was safe. They also ignored the growing number of reports they were receiving about harmful side effects associated with taking the drug. In fact, beginning in 1959, Grünenthal was inundated with complaints from doctors about nerve damage ranging from mild to severe and sometimes permanent, particularly in older people who had used the drug as a sleeping pill.” do we discover in the Oscar-winning documentary No Limits: The Thalidomide Saga from 2016 (available in full at Youtube).
► In April 1970: despite the obvious responsibility of Grünenthal, the company and plaintiffs’ attorneys agree on an amicable agreement and decide to abandon their criminal proceedings to avoid the bankruptcy of the firm which would then deprive the victims of any compensation. In exchange, the firm created a foundation in 1971 – the Hilfswerk für behinderte Kinder – responsible for compensating the victims.
► From 1972 to 1991: in Germany, 538 million Deutsche Marks are paid to 2,866 victims
► In December 2009 : in the United Kingdom, the British government announces an endowment of 20 million pounds sterling to the Thalimonide Trust, an association created in 1973 to help victims.
► In February 2010: Belgium announces the creation of a Foundation to help victims.
► Fromthis pharmaceutical scandal contributed to new legislation which has markedly improved the safety of use of medicines. For example, the modification of American legislation through the Kefauver-Harris Amendment to the Federal Food, Drug and Cosmetic Actand especially the implementation of Marketing Authorization (MA) delivery systems in all the countries of the European Community Commission.
How many babies are born with birth defects?
The number of children born with congenital malformations due to their mothers taking thalidomide during pregnancy is estimated at 15,000 in 46 countries around the world: 3,000 in Germany, and very few in France as the drug was not marketed there (some French women had however obtained it in border countries: Germany, Belgium, Italy, Spain). But it seems difficult to know the exact number of victims of thalidomide, because several infants died before birth, stillborn or who died shortly after birth due to the severity of their malformations (not all of these births were registered, not to mention the infanticides that took place around this time).
Photos of the thalidomide scandal
What are the side effects of thalidomide?
Specifically, thalidomide can inhibit the formation of blood vessels. This is due to different mechanisms which have not all been elucidated to date. However, several hypotheses have been put forward and published by researchers in various scientific journals. We know that thalidomide can have serious effects on the fetus when ingested during pregnancy:
- Shortened bilateral limbs (one or two legs, one or two arms, 4 limbs)
- Missing bilateral members
- Missing fingers or toes
- Webbing of fingers or toes
- Extra fingers or toes
- Partial or total hearing loss
- Partial or total visual loss
- Paralysis (of facial muscles most often)
- Malformation of the digestive tract
- Malformation of the duodenum
- Malformation or absence of anus
- Major organ damage
- Dead
Is thalidomide available in France?
Since 1997, thalidomide has been available in France for certain indications (see below). However, it is not delivered to women who are pregnant or likely to be.
For whom is thalidomide indicated today?
Thalidomide is effective in the treatment or relief of leprosy, systemic lupus erythematosus and certain cancers (multiple myeloma). Indeed, thalidomide is able to slow down inflammatory reactions and the emission of substances stimulating tumor growth. Medicines containing this substance are therefore allowed today in several countries for these uses. In Francetwo drugs containing thalidomide (Thalidomide Accord® And Thalidomide BMS®) benefit from a temporary recommendation for use (RTU), by theMedicines Agency (ANSM) in treatment:
- Severe aphtoses (superficial ulcerations of the oral mucosa)
- Cutaneous forms of lupus erythematosus
- Leprous erythema nodosum
- Active Crohn’s disease
Of course, due to the devastating effects previously mentioned, thalidomide is strictly contraindicated in pregnant women or at risk of becoming pregnant.
Sources: Thalidomide Victims Association of Canada (site in Canada) / Regulating early access to health products (RTU) ANSM / Report of the Thalidomide Task Force of the War Amps of Canadapublished on February 14, 1989 (synopsis in english only).