Frances Kelsey who joined the FDA in the United States in 1960, and who refused to authorise thalidomide for use
| Photo Credit: Public domain, via Wikimedia Commons
In today’s world, rapid advancements in artificial intelligence, communication technologies, social media, and various other fields have revolutionised our daily lives. AI now powers everything from smartphones to self-driving cars, and social media instantly connects us globally. Computing power doubles every two years, as predicted by Moore’s law. Yet, despite this rapid technological progress in electronics, drug development remains a slow and cautious process in healthcare. Why? To answer this, we turn to a dark chapter in history and a heroine born on July 24 who changed the course of pharmaceutical safety.
In the late 1950s, a drug called thalidomide was introduced. Marketed as a sedative and a remedy for morning sickness in pregnant women, it was hailed as a miracle. Morning sickness, characterised by nausea and vomiting, is a common and often debilitating condition experienced by many pregnant women, particularly in the first trimester. Advertised as non-addictive and safe, thalidomide quickly became a bestseller in over 46 countries under names like Contergan in Germany and Distaval in the UK.
However, this miracle soon turned into a nightmare. By the early 1960s, doctors noticed a horrifying pattern: thousands of babies were being born with severe birth defects. Limbs were shortened or absent, organs were malformed, and many of these children did not survive. The culprit? Thalidomide, the so-called wonder drug. Women seeking relief from the misery of morning sickness found themselves faced with a far greater horror—they had rid themselves of nausea only to bear children without limbs.
The drug development landscape in the 1950s and 1960s was vastly different from what it is today. The prevailing belief was that the placenta acted as an impenetrable barrier, protecting the fetus from any potential harm. Consequently, the testing of drugs on pregnant animals was rare, and the concept of teratogenic effects—substances that cause developmental malformations—was not well understood.
Pregnant animals not tested
The initial animal testing for thalidomide had been incomplete. It did not include studies on pregnant animals, a critical oversight with catastrophic consequences. While this tragedy gripped Europe, the United States was largely spared. This was thanks to Frances Kelsey’s vigilance. In 1960, Kelsey joined the Food and Drug Administration (FDA) when she was tasked with reviewing thalidomide’s application for approval in the US. Dr. Kelsey, a trained pharmacologist with a medical degree, approached her work with meticulous care. Despite immense pressure from the drug’s manufacturer, she refused to approve thalidomide without more data on its safety. She was particularly concerned about the incomplete information on the drug’s effects on animals other than mice.
As reports of congenital disabilities linked to thalidomide began to surface in Europe, Dr. Kelsey’s suspicions were confirmed. Her insistence on thorough testing and her refusal to be swayed by pressure saved countless American children from a similar fate. Her stand against thalidomide highlighted the crucial need for stringent drug regulations.
Changes in drug regulation
The thalidomide disaster prompted sweeping changes in drug regulation, just as the Harshad Mehta scam in India acted as an alarm that led to significant stock market reforms by SEBI. The thalidomide tragedy led to substantial changes in the pharmaceutical industry. The United States introduced the Kefauver-Harris Amendment in 1962, which required drugs to be proven safe and effective through rigorous clinical trials before approval. This amendment significantly strengthened the FDA’s oversight, ensuring that no drug could be marketed without solid evidence of its safety and efficacy.
The Kefauver-Harris Amendment mandated that manufacturers provide proof of the effectiveness and safety of their drugs before approval. It also required informed consent from clinical trial participants and established more rigorous procedures for drug advertising. These changes marked a significant shift towards prioritising patient safety over corporate profits.
In this file photograph people born with severe defects are seen waiting for the trial against German company Gruenenthal Group to start at the Court in Madrid, Spain, in 2013
| Photo Credit:
AP
Teratology gains significance
The thalidomide disaster also gave rise to the field of teratology, the study of congenital disabilities. Scientists began to understand how certain substances could disrupt foetal development, leading to stricter guidelines and more comprehensive testing of new drugs. Today, safety is prioritised over speed, ensuring that new medications undergo extensive evaluation before reaching the public.
Despite its dark past, thalidomide has found new life in modern medicine. Under strict regulations, it treats conditions including leprosy, multiple myeloma, and certain cancers. This transformation from a catastrophic drug to a valuable treatment underscores the complexities of pharmaceutical science.
The victims of the thalidomide disaster in Europe faced prolonged struggles for recognition and compensation. Initially, the pharmaceutical company behind thalidomide, Chemie Grünenthal, denied responsibility and even tried to blame the congenital disabilities on nuclear testing. It took pressure groups and decades of advocacy for the victims to receive compensation. Remarkably, it wasn’t until 2012—50 years after the disaster—that Chemie Grünenthal issued a formal apology.
The power of vigilance
Dr. Frances Kelsey’s legacy is a testament to the power of vigilance and ethical responsibility in drug development. Her commitment to safety over profit prevented a nationwide tragedy and set a gold standard for drug regulation. 1962, Dr. Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service, the highest honour given to a civilian federal employee. Today, drug development is a slower, more cautious process compared to rapid technological advancements. But this deliberate pace ensures that new medications are safe, protecting public health.
In conclusion, the thalidomide disaster serves as a powerful reminder of the responsibilities that come with pharmaceutical innovation. It underscores the importance of rigorous testing and ethical considerations in drug development. Despite its horrific past however, thalidomide’s contributions to medicine today remind us that even from the darkest moments, positive change can emerge.
(Dr. C. Aravinda is an academic and public health physician. aravindaaiimsjr10@hotmail.com)
