Introduction
Thalidomide is a medicinal drug that was developed in the 1950 by the Western German Company Chemie Grünenthal, and was sold and distributed in 46 countries, marketed by 14 pharmaceutical companies1. This medicine created catastrophic impacts on the lives of individuals, and it was only 5 years after thalidomide became widely available over the counter that the connection was made between the drug and its effects on pregnant women and their children, who had birth defects due to thalidomide. Since the ‘thalidomide scandal’, as it became known, led to a series of legal battles and settlement disbursements, as well as huge changes in the way in which drug trials are now conducted and the safety of all drugs.
Intended use
The original intended use of thalidomide was as a sedative or tranquilizer, but then began to be used to treat a variety of other illnesses – such as colds, flu, nausea, and morning sickness in pregnant women1. While thalidomide was being researched and developed into a drug suitable for human use, it did not undergo any clinical trials involving humans. Instead, testing was solely carried out on animals, and it was determined in the early stages of this research the rodents were supposedly able to be unaffected by a dose of thalidomide which was over 600 times the normal human dose2. Unfortunately, it was only after the link between thalidomide and birth defects was made that it was questioned how this drug was even made available for human use, especially as it was readily available from pharmacies without the need for a prescription. These queries led to an investigation in which it was discovered that extensive tests beyond animal testing into thalidomide had not taken place – and thus the drug should not have been declared safe to use. However, thalidomide was deemed to be harmless to humans, and was licensed in Germany in July 19561.
Treatment for morning sickness
Although the most infamous large-scale side effect of thalidomide is the foetal birth defects it caused, this drug additionally caused a multitude of serious health hazards – which were ignored by Chemie Grünenthal from when many reports about these problems began inundating the company from as early as 1959. One such side-effect of thalidomide is peripheral neuritis3, which is a type of nerve injury that can be anywhere in the body. This damage will start with a tingling sensation in the feet and hands, then numbness and following by feeling cold. Severe muscular cramps are often another symptom of peripheral neuritis, and other effects can include limb weakness and loss of coordination. Whereas some of the symptoms can be treated to improve them or remove them completely, it is more common that they are irreversible.
While thalidomide was not intended to be used specifically as a treatment for morning sickness for women in the early stages of their pregnancy, this drug was found to be relatively effective in relieving this problem. When thalidomide started to be produced and sold in the UK from 1958, it was produced by ‘The Distillers Company (Biochemicals) Ltd’. One of the brand names which thalidomide was sold under was Distaval. On the advertisement for this brand, it was stated that: “Distaval can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child.”1 Not only was there a lack of evidence to prove this claim, but also pregnant women were taking it under false guidance, and many were even prescribed it.
Chemistry of the drug
The chemical formula of thalidomide is C13H10N2O4 and has the scientific name ‘a-(N-Phthalimido)glutarimide3.
(4)
Thalidomide exists as two isomers, which are mirror-images of each other. The (R)-Enantiomer has sedative effects and explains why thalidomide was so effective when it was used as a medication for sedation and tranquilisation. The (S)-Enantiomer, however, is teratogenic. Teratogenic drugs are agents which can affect an embryo or fetus’ development and can cause congenital malformations5. The thalidomide that is sold as medication is a mixture of these two forms, as these isomers interconvert under biological conditions, rendering the process of separating them before the drug is distributed and used ineffective.
The infamous consequences of thalidomide
Tragically, thalidomide is most well-known for the widespread birth defects it caused – and the first child who was affected by the taking of thalidomide was born on 25th December 1956 to an employee of Chemie Grünenthal. If a pregnant mother took thalidomide, this could culminate in a series of disabilities including, but not limited to: shortened limbs, missing limbs, sensory impairment, facial palsy, damage to the eyes and ears or lacking ears and ears, brain damage, and impacts on the skeletal structure6. As to the location of the birth defect on the body pertained to the day or days which the pregnant mother took thalidomide – and even a single day could be the difference between lacking limbs and brain damage. In a video produced by the Science Museum about what it is like to be affected by thalidomide, Dr Martin Johnson (Chairman of The Thalidomide Trust) speaks about how the days on which thalidomide was taken can cause specific congenital defects7. He discusses that, if thalidomide were taken around day 20 of the pregnancy, this would cause central brain damage in the child. If the drug were taken on day 21, the eyes would be impacted, and if it were taken on days 22 to 23, the ears and face would be affected, and hearing would almost certainly be greatly impaired. Thalidomide was only found to affect the foetus if the mother took the drug between 20 and 37 days after conception – and outside of this window, thalidomide would not have any effect1.
Thalidomide was available as a medication from 1956, though only in Germany, and became obtainable throughout much of Europe and some countries in Asia (like Japan) later in the 1950s. It was on the 26th of November 1961 that thalidomide, under all brand names, was formally withdrawn by its creator Chemie Grünenthal. In less than five years this drug was widely distributed and sold, it is estimated that over 100,000 babies were affected by it globally – approximately half of which died only months after birth1. Currently there are less than 3,000 people who were babies affected by thalidomide.
Individuals affected by thalidomide
The Thalidomide Trust, a charity which supports those born with birth defects as a result of thalidomide, carried out a survey amongst its beneficiaries, in which it showed that over 90% of them experienced severe and/or continuous pain often. Low mental health is, unfortunately, another health problem typically associated with those living with thalidomide-related disabilities, especially depression, anxiety, and loneliness.
Of the babies affected by thalidomide that survived beyond the first few months of infancy, Louise Medus was one. Louise was born on the 23rd of June 1962, to her father David Mason, and her mother Vicki Mason – who had been prescribed thalidomide during her pregnancy only weeks before the drug had been recalled en masse. Louise states in an article by the Guardian8: “Like the other parents of thalidomide parents, I’m sure they [her parents] were expecting a fully formed baby and some of us didn’t have arms, some of us didn’t have legs, some of us didn’t have arms of legs.” Louise published her memoir in 1988, entitled ‘No Hand To Hold & No Legs To Dance On’.
As a result of the fatal and irreversible damage attributed to the drug thalidomide, large settlements were due to those affected. The Distillers Company (Biochemicals) Ltd, which was the company that sold thalidomide as a drug in the UK, agreed to a final settlement in 1973 to pay damages to 429 people in the UK who had been affected by thalidomide from birth. Additionally, the Thalidomide Trust was established, in which thalidomide survivors are able to receive support and annual grants6.
9In New Zealand and Australia, Diageo (the parent company of The Distillers Company (Biochemicals) Ltd) paid AU$89 million to approximately 100 individuals in compensation. As recently as in 2014, it was ruled by a court that in Spain, the company Grunenthal (another seller of thalidomide) would pay €35 million to 22 people affected there. Yet there are approximately 180 people in Spain still seeking compensation.
(10) In June 1961, an article promoting the taking of thalidomide in the third trimester of pregnancy was published, claiming to be written by a ‘R.O. Nulsen, M.D.’ but was in fact written by the medical director of Chemie Grünenthal. In the early 1960s when birth defects were being noticed and linked to thalidomide, Chemie Grünenthal obscured these findings from public view and refused to take responsibility for creating thalidomide – which was the cause of them. It was around 6 months after the article allegedly written by a Dr Nulsen that this evidence was made public in Germany.
Horrifyingly, the drug company Chemie Grünenthal did not publicly apologise to those affected by thalidomide until 2012 – approximately 50 years after the drug was first released.
Current research and future treatment prospects
Despite the tragic results that transpired from the use of thalidomide, this drug continues to be researched presently and now presents auspicious results in treating conditions such as types of cancers and leprosy. According to the Mayo Clinic11, it has been determined that thalidomide helps regulate the body’s immune system, control inflammation and slows the processes of creating new blood vessels – which cancers utilise in order to grow and spread throughout the body. The US Food and Drug Administration (FDA), on the basis of research like this, has approved thalidomide in use for treating erythema nodosum leprosum (skin lesions caused by leprosy) and multiple myeloma.
Additionally, in 1964, a doctor in Jerusalem called Dr Jacob Sheskin, administered thalidomide to a patient with leprosy in order to act as a sedative and help the patient to sleep2. Surprisingly, the effects of the thalidomide were remarkable – and the leprosy appeared to have been cured. However, the condition returned once the patient stopped taking thalidomide, and so it was determined that thalidomide was suppressing the disease rather than treating it.
Furthermore, another example of the positive effects of thalidomide is when it was utilised as a treatment method against mantle cell lymphoma11. In 1996, a man named Garry Edling was diagnosed with this condition, but the cancer became progressively worse despite five rounds of chemotherapy and a stem cell transplant. Garry was treated by the consultant Dr Simon Rule, who prescribed him thalidomide based on Dr Sheskin’s plan: to improve symptoms and to prospectively alleviate pain. Garry receives thalidomide as part of a drug trial, as this drug remains unlicensed in the UK and can only be prescribed under severest caution. When he began taking the drug, Garry’s tumours began shrinking, and Dr Rule said, “his response is nothing short of remarkable”. On the other hand, Garry has suffered from side effects such as muscular pain, and numbness in his hands and feet – yet this is the cost of prolonging his life.
Consequential legislation
The thalidomide tragedy also led to the creation of the 1968 Medicines Act in the UK, as the UK government wanted a greater stronghold over the regulation of the drug industry. This act classes medical drugs into three categories12: general sales list medicines, pharmacy medicines, and prescription only medicines. General sales list medicines are able to be sold by any shop, but pharmacy medicines can only be sold in a pharmacy – though a prescription is not necessary. Prescription- only medicines are the category with the highest level of restriction: they can only be sold by a pharmacist if prescribed by a doctor.
In the USA, after thalidomide was prohibited from being distributed and sold, the Kefauver-Harris Amendments were made in 1962 to the 1938 Food, Drug, and Cosmetic Act13. This meant that there were strict guidelines instigated for the process of drug approval in the United States – crucially requiring drugs to be safe as well as effective before being approved for medical use.
Conclusion
To conclude, thalidomide is an infamous drug with a fatal and horrifying history, causing thousands of birth defects and deaths in infants. This drug was not researched and studied thoroughly enough to warrant it being approved, licensed, and widely distributed – and even prescribed – to unknowing individuals. In spite of this horror, the thalidomide tragedy has meant that there has been improved legislation in place to improve the safety of future drugs and prevent the same consequences from occurring again. Furthermore, thalidomide is now being utilised in an effective way to treat conditions like leprosy and is yielding positive results. The consequences of thalidomide are tragically irreversible, but fortunately this drug can now be directed towards improving lives, and with anticipation another tragedy like it will not arise again.
Samara Macrae, Youth Medical Journal 2022
References
1. Science Museum: “Thalidomide” – https://www.sciencemuseum.org.uk/objects-and-stories/medicine/thalidomide
2. BBC one: “The return of Thalidomide” – http://www.bbc.co.uk/insideout/southwest/series7/thalidomide.shtml
3. Victims Association of Canada: “What is Thalidomide?” – https://thalidomide.ca/en/what-is-thalidomide/
4. Wikimedia Commons: “Thalidomide enantiomers” – https://commons.wikimedia.org/wiki/File:Thalidomide-enantiomers.png
5. MedicineNet: “Medical Definition of Teratogenic drugs” – https://www.medicinenet.com/teratogenic_drugs/definition.htm
6. The Thalidomide Trust: “About Thalidomide” – https://www.thalidomidetrust.org/about-us/about-thalidomide/
7. Science Museum: “What it’s like to be affected by Thalidomide” – https://youtu.be/LcXm6MEte9U
8. The Guardian: “My thalidomide family: Every time I went home I was a stranger” – https://www.theguardian.com/lifeandstyle/2014/aug/01/thalidomide-louise-medus-a-stranger-when-i-went-home
9. The Conversation: “Why thalidomide survivors have such a tough time getting compensation” – https://theconversation.com/why-thalidomide-survivors-have-such-a-tough-time-getting-compensation-47164
10. Retro Report: “Thalidomide: Return of an Infamous Pill” – https://www.youtube.com/watch?v=gzEdbbyww9U
11. Mayo Clinic: “Thalidomide: research advances in cancer and other conditions” – https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/thalidomide/art-20046534
12. DrugWise: “Drug laws” – https://www.drugwise.org.uk/drug-laws/
13. The Embryo Project Encyclopaedia: “US Regulatory Response to Thalidomide (1950-2000)” – https://embryo.asu.edu/pages/us-regulatory-response-thalidomide-1950-2000
Youth Medical Journal 
One reply on “Thalidomide: Horrifying Tragedy of the Past, Auspicious Treatment of the Future”
Covid vaccines are the modern day version of thalidomide. They have not been through adequate safety trials and were rushed. Rushing drug development causes all sorts of mistakes.
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