The Thalidomide Tragedy: The Event That Gave Rise to Modern Drug Safety Assessment

Thalidomide is a drug that was first commercialized in the 1950s, mainly as a  morning-sickness treatment for pregnant women. However, the drug was soon  observed to produce severe birth defects when consumed during pregnancy,  resulting in around 10.000 affected infants worldwide (1). This medical  catastrophe has served as an early example on why medicines have to go under  strict testing before being commercialized and continue to be monitored overtime,  setting the principles of current pharmacovigilance procedures (2). 

Thalidomide Origins 

Thalidomide was first developed by the Swiss pharmaceutical company CIBA in  1953, to be later commercialized by the German pharmaceutical company  Chemi-Grunenthal in 1956 (1). The drug was first released as a sedative to treat  anxiety, stress and insomnia. Importantly, thalidomide was considered to be a  safe alternative to the existing barbiturate medication, which is known to be highly  toxic and addictive (3, 4). Soon after release, thalidomide was observed to have  antiemetic effects, meaning that it relieves nausea and vomiting. Thus, it was  marketed as a treatment against morning-sickness for pregnant women and  became one of the best-selling drugs worldwide, distributed in 46 different  countries (3). One important contributing factor was the drug’s ease of 

accessibility. It did not require a prescription, was relatively inexpensive to  purchase in pharmacies, and sample packages were distributed to physicians for  free provision to patients suffering from morning-sickness. (1, 3) 

The Thalidomide Tragedy 

After some time in the market, reports started surfacing of patients developing  peripheral neuropathy after thalidomide treatment, which translates into nerve  damage and a feeling of numbness, tingling, burning pain and reduced sensation  on hands and feet. Moreover, reports of severe birth defects affecting multiple  body systems were also coming to light, but they were initially disregarded (1, 3).  Interestingly, in spite of the pressure to do so, thalidomide was not approved in  the USA at the time. This was thanks to the intervention of FDA supervisor Dr.  Frances Kelsey, who was concern with said safety reports, avoiding a national  medical catastrophe (3). 

It was not until 1961 that these safety concerns were taken into serious  consideration, when Australian obstetrician Dr. William McBride and German  geneticist Dr. Widukind Lenz made strong independent reports linking  thalidomide use during pregnancy to severe birth defects (1). These physicians  observed that the rates of reported birth malformations in babies had increase  from 1.5% up to 20% in women who had taken thalidomide during pregnancy (5).  It is estimated that 10.000 infants were affected, 40% of them dying before  reaching 1 year of age, the rest facing severe handicaps that reduced their life  quality. Of note, stillborn babies and miscarried pregnancies were not included in  these statistics; the real number of affected pregnancies is unknown. Thalidomide  birth malformations come at a wide range and consist of deformed limbs, face,  eyes, ears and genitalia; as well as damage of internal organs such as heart,  kidney, and gastrointestinal tract. As a result, thalidomide was withdrawn from the  global market in 1962 (1, 3). 

Consequences: Changes in Drug Safety Assessment 

The thalidomide tragedy has re-shaped how we currently approach medicine  safety systems, both in the pre-approval testing phase and the post-marketing  safety surveillance (2, 5).  

As for the pre-approval clinical research phase, there are two concepts that have  been introduced since. The first one is the inclusion of teratogenic studies, which  aim to test whether or not a drug causes birth defects in embryos (5). This type  of test was not required at the time thalidomide was first commercialized (1). The  second concept is the acknowledgement that different animal species can have  different responses to drug treatments (5). Thalidomide initial tests had only been  conducted in mice, which happen to be less sensitive to the drug than humans  and later tested species such as rabbits or primates (3). Thus, no toxic effects  were reported in the initial thalidomide studies (1). Since this discovery, it is 

mandatory to test the response of any drug in several animal species before  commercialization (5). 

Another important introduced aspect is the concept of pharmacovigilance.  Pharmacovigilance is the process of monitoring the safety of medicines once they  are introduced in the market. This involves a systematic, organized and regulated  process to report any adverse effects patients may experiment after taking a  specific medicament; as well as a compromise to take action to reduce medical  risks (5). In 1968 the World Health Organization (WHO) initiated a global  monitoring system to detect early signs of possible harms caused by medicines  after their release for general use, which is one of the main pillars of the current  medicine safety framework (2). 

Thalidomide Use Nowadays 

As a side note, thalidomide was reintroduced in the market in the 1990s.  However, it does not serve its original purpose. After market withdrawn,  thalidomide was discovered to have anti-inflammatory effects, which is useful to  treat various inflammatory diseases like erythema nodosum leprosum, a painful  inflammatory complication of leprosy (6). Moreover, it is used to treat multiple  myeloma, an aggressive type of blood cancer. Here, thalidomide anti 

inflammatory effects are beneficial, but more so its anti-malignant and  antiangiogenesis properties. This means that thalidomide limits the formation of  new blood vessels around the bone marrow, reducing its oxygen and nutrient  supply, thus preventing tumour growth (6). Thalidomide intake is nowadays highly  monitored because of its high toxicity and, of course, forbidden during pregnancy  (6). 

References 

1. Rehman W, Arfons LM, Lazarus HM. The rise, fall and subsequent triumph of  thalidomide: lessons learned in drug development. Ther Adv Hematol. 2011  Oct;2(5):291–308. doi:10.1177/2040620711413165. PMID: 23556097. 

2. Medsafe. The Medsafe Files, Episode Six: Global Pharmacovigilance  [Internet]. Wellington (NZ): New Zealand Medicines and Medical Devices  Safety Authority; 2018 Jun [cited 2026 May 22]. Available from:  https://www.medsafe.govt.nz/profs/PUArticles/June2018/TheMedsafeFiles6 

GlobalPharmacovigilance.htm 

3. Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms.  Birth Defects Res C Embryo Today. 2015 Jun;105(2):140–156.  doi:10.1002/bdrc.21096. PMID: 26043938. 

4. Skibiski J, Abdijadid S. Barbiturates. In: StatPearls [Internet]. Treasure Island  (FL): StatPearls Publishing; 2025 Jan [cited 2026 May 22]. Available from:  https://www.ncbi.nlm.nih.gov/books/NBK539731/

5. Fornasier G, Francescon S, Leone R, Baldo P. An historical overview over  pharmacovigilance. Int J Clin Pharm. 2018 Aug;40(4):744–747.  doi:10.1007/s11096-018-0657-1. PMID: 29948743. 

6. Aschenbrenner DS. Thalidomide. In: StatPearls [Internet]. Treasure Island  (FL): StatPearls Publishing; 2025 Jan [cited 2026 May 22]. Available from:  https://www.ncbi.nlm.nih.gov/books/NBK557706/

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