For centuries, it has been debated if human beings are inherently good or inherently evil. Just ask English philosophers, Thomas Hobbes and John Locke, who famously debated the question themselves before the rise of the 18th century. Thomas Hobbes believed that human beings were inherently evil, whereas John Locke believed that human beings were inherently good. The debate was never won.

When it comes to the inherent nature of drugs, we’re of neither mind. To us, drugs aren’t inherently good or evil; it’s the context that matters and defines their usage.

Read our blog to see how the drugs, thalidomide and sodium valproate, have danced between being called Dr. Jekyll and Mr. Hyde, depending on the context of their usage, and discover the lessons learned from this tale of two contexts.

Becoming Mr. Hyde

“It takes many good deeds to build a good reputation, and only one bad one to lose it.”

— Benjamin Franklin

Thalidomide and sodium valproate both earned the reputation of being an evil drug, despite being hailed as a “Wonder Drug” early on in their discovery. Before scandal plagued these drugs, both were commonly used to treat a variety of ailments and diseases. Thalidomide was heavily prescribed as a tranquilizer, and sodium valproate was prescribed to treat epilepsy and bi-polar disorder.

When used in these contexts, the drugs did what they were designed to do. It was only when thalidomide was repurposed to treat morning sickness in pregnant women and women taking sodium valproate began to fall pregnant that the harmful effects of these drugs were discovered; and by then it was too late.

Thalidomide was originally developed as a tranquilizer in 1957 in response to the demand for sedatives across the United States and Europe. According to Helix’s article, 1 in 7 Americans were taking sleeping pills at the time. By 1960, thalidomide was marketed and sold over-the-counter in 46 countries.

Thalidomide became Mr. Hyde when it was quickly repurposed specifically to treat morning sickness in pregnant women without proper testing. Thalidomide was never made for this target population, but nevertheless the drug was advertised to pregnant women as perfectly safe to take for both them and the baby. This ended up not being true and their babies were sadly born with shortened or missing limbs. Thalidomide was banned in 1961 as a result.

Sodium valproate‘s story is a little different. Sodium valproate was used to treat its intended target population, but it became Mr. Hyde when it was discovered to have an unintended knock-on effect in pregnant women.

When women who were taking sodium valproate for epilepsy or bi-polar disorder fell pregnant, it was revealed that the drug had an adverse effect on their children. When sodium valproate was taken in this context, the drug was found to cause physical abnormalities, developmental delays and autism in the children of mothers who took the drug during pregnancy. These mothers were unaware of any risks or possible side effects when they were prescribed and agreed to take the drug, and were sadly ignored by the health system when reporting their symptoms, which were simply chalked up as “women’s problems.”

Unfortunately, the drug’s safety wasn’t spotted quick enough and thus caused immense suffering on countless women who took the drug for a pre-existing condition and not pregnancy.

Returning to Dr. Jekyll

“It is during our darkest moments that we must focus to see the light.”

— Aristotle

Out of every tragedy comes hope.

Despite the dark past of thalidomide and sodium valproate, these drugs do have their place in modern medicine.

In the case of thalidomide, we have Dr. Jacob Sheskin to thank for returning the drug to its Dr. Jekyll state – although he didn’t even intend to at the time!

Dr. Jacob Sheskin worked in a leper colony in Jerusalem, Israel in 1964 as a doctor at Hadassah University Hospital. He was treating a man who contracted leprosy and wanted to help him sleep better, as he was in agonising pain throughout the day. Thalidomide, being a tranquilizer, was the ideal drug to prescribe to him and Dr. Sheskin did just that. Three days later, he found a new application for the drug!

Thalidomide was found to actually heal the patient’s leprosy skin lesions. When Dr. Sheskin stopped prescribing thalidomide to his patient, he saw that the skin lesions reappeared and worsened. Although he couldn’t cure the patient of the disease, he could help to stop the painful symptoms from occurring. Dr. Sheskin just repurposed a drug by chance!

Fast forward to today, and thalidomide is now an FDA-approved drug for leprosy and multiple myeloma, which is a type of blood cancer. Because of its scandal back in the early 1960s, thalidomide is heavily regulated by the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program. The S.T.E.P.S. program ensures that patients and pharmacists understand the risks of taking and prescribing thalidomide with clear product labelling, educational materials and consent forms.

Dr. Sheskin’s story shows that context is key when discussing the history and usage of a drug. In his particular context, he helped to transform a patient’s life. This man was living with a chronic, terminal illness and Dr. Sheskin provided relief and hope for a better quality of life. His story is a testament to the fact that a drug can make the right difference, to the right patient, when given in the right context.

Where does this leave sodium valproate? Today, sodium valproate is still widely used for its original purpose of treating epilepsy and bi-polar disorder. Because of the scandal in the 1990s, sodium valproate is no longer prescribed to pregnant women. Doctors now understand the full risks, benefits and usage of the drug, thus allowing them to address patient safety concerns immediately and ensure that the drug is taken safely.

In terms of repurposing the drug, sodium valproate is now being looked at as a possible repurposed treatment for the rare disease, Wolfram Syndrome, at The University of Birmingham. Timothy Barrett and his team found that sodium valproate can cross the blood-brain barrier and increase the expression of Wolfram protein, ER chaperone and p21cip in affected cells.

It is because of the sodium valproate scandal in the 1990s that Birmingham’s clinical trial team now has a complete safety profile of the drug. They know and understand the risks, benefits and possible side effects of taking the drug, and can now use it effectively and ethically to potentially delay the progression of Wolfram Syndrome in patients.

A Tale of Two Contexts: The Lesson Learned

As you can see, depending on the context, these drugs take on two very different lives: one positive and one negative. If there is anything to take away from this tale, it is this: thorough clinical research must be done to ensure the safety of patients before bringing any treatment to trial or market. Sales cannot come before patient safety. Rushing a new “Wonder Drug” through drug development and testing without adhering to patient safety and regulation will only lead to undue harm. Accurate and exhaustive clinical data is needed to fully understand a drug’s makeup and composition before looking to bring it to patients. Nothing can compensate for a lack of scientific knowledge, evidence or data.

The thalidomide and sodium valproate scandals revealed what a drastic oversight in patient safety and regulation can result in. At Findacure, we often talk about the power of drug repurposing, as it helps to accelerate research and bring new treatments to patients quickly. We tell this tale of context because we want to highlight the importance of ensuring that a drug which is being rushed to clinical trials in an effort to save time is rigorously tested, monitored and approved before reaching patients. Every repurposed drug must be clinically proven to do no harm and demonstrate its ability to make a positive, measurable impact on a patient’s life. Only then is a drug repurposing project successful and safe.

Want to learn more? Watch our webinars “Intro to Drug Repurposing for Small Patient Groups” and “Drug repurposing as a strategy for rare disease charities” below!