Today, we take drug safety for granted. But this certainty came at a tremendous cost. Between the 1950s and 1960s, a drug marketed as completely safe, forever changed the history of pharmacovigilance, leading to one of the worst pharmaceutical disasters of the 20th century: Thalidomide. Prescribed for anxiety, insomnia, and morning sickness during pregnancy, Thalidomide was considered a breakthrough medication. However, its mechanism of action turned out to be devastating: by interfering with fetal development, it caused severe birth defects, including phocomelia, a condition in which limbs are shortened or absent.
What is Thalidomide?
Thalidomide is an active substance with sedative and immunomodulatory properties, developed and marketed in the 1950s by the German pharmaceutical company Chemie Grünenthal. Initially, it was used as an active compound in medications for treating anxiety and insomnia. Unlike other sedatives of the time, it appeared to have an excellent safety profile: it did not cause addiction like barbiturates, showed no obvious signs of toxicity in adults, and was promoted as a “safe-for-all” drug—to the point that, in some countries, it was even available without a prescription. Its widespread use took off when it was found to be effective in treating morning sickness during pregnancy. It seemed like the perfect drug: effective, well-tolerated, and free of noticeable side effects. But the reality was far different.
Why was Thalidomide considered safe?
At the time, there were no standardized protocols to assess the effects of drugs in humans. Clinical trials were often conducted without strict regulations, failing to consider long-term effects, and there were no clear guidelines for testing drugs on vulnerable populations, such as pregnant women or children. Additionally, teratogenicity testing (evaluating the potential harm to fetal development) was not mandatory, as it was wrongly assumed that the placenta would protect the fetus from chemical substances. For these reasons, Thalidomide was tested on animals without assessing its impact on fetal development, and human clinical trials were conducted on a limited number of healthy volunteers. In some cases, it was even tested on psychiatric patients and prisoners, without any long-term evaluation or consideration of its use during pregnancy. Since no immediate risks emerged from the studies, the manufacturer declared that Thalidomide was “virtually non-toxic.” It was subsequently marketed in 46 countries, spreading rapidly in Germany, the United Kingdom, Australia, Canada, Brazil, and Japan, where it quickly became popular as a sedative and anti-nausea drug.
Why did Thalidomide turn into a global tragedy?
Unfortunately, Thalidomide was not only considered safe based on incomplete testing, but its mechanism of action was also poorly understood. While its sedative and anti-inflammatory properties were well known, scientists were unaware that it inhibited the formation of new blood vessels (angiogenesis)—a process crucial for proper fetal development. Additionally, it damaged neural crest cells, which are essential for the development of limbs, facial structures, and internal organs. The consequences were catastrophic: thousands of babies were born with severe limb deformities, including phocomelia (shortened limbs) or amelia (complete absence of limbs). In other cases, infants suffered from organ malformations or died due to spontaneous abortion. No one had anticipated that a drug harmless to adults could have such a devastating impact on fetuses.
Terry Wiles, Thalidomide victim, with his father Leonard
One report can make a difference
In 1961, Australian gynecologist William McBride began noticing a disturbing trend. Before 1956, phocomelia was an extremely rare condition, occurring in only 1 in 100,000 newborns. However, between the late 1950s and early 1960s, in countries where Thalidomide was widely used, the incidence skyrocketed to 1 in 2,000 births. McBride suspected a link between the drug and the birth defects. Concerned by his findings, he wrote a letter to The Lancet, one of the world’s most prestigious medical journals, warning about the potential dangers.
At the same time, German pediatrician Widukind Lenz conducted a detailed epidemiological study, which confirmed the correlation between Thalidomide and neonatal malformations. In November 1961, he presented his findings at a pediatrics conference in Düsseldorf, increasing pressure on health authorities.
Their warning was crucial. The scientific community acted swiftly, and in December 1961, Thalidomide was withdrawn from the market. This event marked the beginning of modern pharmacovigilance: for the first time, a doctor’s report led to the global withdrawal of a drug. The case demonstrated a critical lesson: every report can make a difference saving thousands of lives.
Thalidomide and the lesson for drug safety
The Thalidomide case forever changed pharmaceutical safety. Today, every drug undergoes rigorous testing before approval. But pharmacovigilance does not end there: monitoring continues even after commercialization, and the role of healthcare professionals and pharmaceutical companies is essential. Reporting an adverse drug reaction is not just a regulatory obligation, it is an act of responsibility. The Thalidomide tragedy taught us a crucial lesson: every report can make a difference.
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