Thalidomide, past and present

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Thalidomide is widely regarded as the worst drug disaster in history for its role in causing thousands of congenital malformations. This post attempts to provide a brief overview of how the tragedy came about and outlines how the same drug has now made a comeback in the treatment of cancer and leprosy.

Thalidomide was developed in West Germany in 1954 by a pharmaceutical company that was attempting to produce low-cost antibiotics. The drug displayed no antibiotic properties but was found to act as a sedative. It was labelled non-toxic as extremely high doses were given to rats, mice, guinea pigs, rabbits, cats and dogs with no apparent side effects. No further testing was done before the drug was released commercially in 1957. Sold in 46 countries worldwide, thalidomide quickly became a best-selling medication and in many places it was nearly as popular as aspirin.

Lauded as a completely safe alternative to barbiturate sleeping tablets, thalidomide was used in the treatment of anxiety, insomnia and seizure disorders. Patients reported that the drug had a calming and sleep inducing effect. After it was found to have antiemetic properties it was commonly prescribed for women suffering from morning sickness in the first trimester of pregnancy.

Concerns arose when doctors began to report that some patients who had been taking the drug were developing signs of nerve damage known as peripheral neuritis. Even more alarming was the unusually high rate of babies being born with malformations. In particular, phocomelia – a rare congenital condition in which the limbs are stunted or missing – appeared at a level never previously seen. By 1961 thalidomide had been banned and withdrawn from the international market after use of the drug was linked to the incidence of these severe birth defects.

Between 1957 and 1961 an estimated 40 000 people developed peripheral neuritis and 12 000 infants were born with malformations. In addition to missing or shortened limbs, deformities included blindness, brain damage and the absence of internal organs. More than half of these children died within their first year while the survivors suffered lasting disability. The thalidomide tragedy resulted in improved drug testing procedures and many survivors have received compensation awarded through high profile lawsuits.

Given the effects of the tragedy, it it surprising to note that thalidomide is still used today as the result of a serendipitous discovery made after the drug was banned. In 1964 the Israeli doctor Jacob Sheskin was caring for a patient with erythema nodosum leprosum, a painful dermatological complication of leprosy. After finding an old bottle of thalidomide in a cupboard he gave it to the patient to help him sleep because the man was dying and in a lot of pain. To his surprise the man slept soundly and awoke feeling better the following morning. New clinical trials supported this discovery and thalidomide revolutionised the treatment of leprosy by improving the management of erythema nodosum leprosum.

Thalidomide has also been approved for the treatment of some types of cancer and is particularly effective for multiple myeloma after attempts at standard therapies such as chemotherapy have proven unsuccessful. Research has shown that the drug inhibits the growth of new blood vessels from pre-existing ones (a process known as angiogenesis). Tumours are unable to grow without a steady blood supply; thalidomide prevents the proliferation of malignant cells by reducing the angiogenesis of surrounding blood vessels.

It has been proposed that the drug’s effect on neural tissue and blood vessel development is the mechanism for the birth defects seen in the late 1950s and early 1960s. Although it is now known that pharmaceuticals can cross the placenta, at that time it was thought to be a barrier that protected the foetus from the harmful substances the mother was exposed to. Angiogenesis of the placenta is crucial for foetal development and the transfer of oxygen, nutrients and wastes. The first trimester of pregnancy is a critical period for the development of basic body structures and organ systems and it appears that a restriction in vascular growth resulting from the drug seriously impacted this process.

Sadly there is a second generation of thalidomide victims in the babies born to Brazilian women taking the drug for the treatment of leprosy. Researchers are currently working to develop a safe analogue of thalidomide that can be administered to leprosy and cancer patients without the risk of causing birth defects.

Image credit

Derer, M. (1998). Thalidomide [Image]. Retrieved from https://www.flickr.com/photos/duckwalk/9636420141

References 

Goldman, D. A. (2001). Thalidomide use: past history and current implications for practice. Nursing Oncology forum, 28(3), 471-477.

Silverman, W. A. (2002). The schizophrenic career of a “monster drug”. Pediatrics, 110(1), 404-406.

TV review of Call the Midwife

Call the Midwife is a highly-acclaimed BBC drama series that follows a group of midwives working in the Poplar district in London’s East End during the late 1950s. Inspired by the memoirs of Jennifer Worth, the programme combines engaging plotlines with accurate scientific information about childbirth and midwifery as it was practised in that period.

For the purposes of this post, I will limit my discussion to the pilot episode, which focuses the arrival of newly qualified young nurse Jenny Lee at the nursing convent of Nonnatus House. She struggles to adjust to the poverty, squalor, and hardship that she is faced with in the dockland slums as well as the challenges of treating expectant mothers in these unsanitary conditions.

For a drama series, Call the Midwife displays an impressive level of attention to detail in its portrayal of midwifery in the 1950s. The nurses cycle around the district carrying a box of tools (such as soap, dressings, forceps, and scissors) and as depicted in the television programme, midwives were actually issued with a case of equipment and a bicycle for transport (Rhodes, 1999). They were also expected to advise expectant mothers on diet and hygiene and provide ongoing ante-natal, post-natal and neo-natal care (Rhodes, 1999). Like the character of Jenny, the majority of women trained as nurses before undergoing additional training in midwifery and most became respected members of their communities (Rhodes, 1999).

Midwives were expected to work independently and call a doctor for assistance only during emergencies (Rhodes, 1999). This medical hierarchy and code of practice is reflected onscreen when a woman begins haemorrhaging after going into premature labour and Jenny calls a doctor for assistance. The midwives are portrayed as caring and competent professionals dedicated to improving the health of their communities.

Call the Midwife is also interesting from an historical perspective as it reflects the scientific knowledge of the time. For example, people appear unaware of the harmful effects of tobacco on foetal development as the pregnant women in the waiting room of the community ante-natal clinic are pictured smoking. It also portrays a number of anachronistic methods and procedures. Both shaving and hot water enemas are no longer performed by midwives during labour as they increase the risk of complications but are represented as routine procedures at the time (Rhodes, 1999). Episiotomies, such as the one Jenny performs on her first patient, have likewise fallen out of favour (Rhodes, 1999).

The series also alludes to broader social trends and attitudes related to childbirth. All women give birth at home without pain relief, as was the case up until the 1960s when maternity hospitals became more widely established in Britain (Creaser, 2013). By 2011 just 2.4% of births in England and Wales took place in the home (Creaser, 2013). In the 1950s fathers were not allowed to be in the delivery room to watch their children being born as it was considered improper for a man to see his wife in labour (Rhodes, 1999). Call the Midwife is accurate in this respect as the delivery room is depicted as an exclusively female domain and the nurses express disapproval when a woman’s husband insists on being present at the birth of his son.

Contextually, the episode reflects demographic trends prior to the introduction of the contraceptive pill. Jenny is amazed by the size of the families in the district and attends to a local woman who is giving birth to her 25th child. Sister Evangelina later informs her that 80 to 100 babies are born each month in Poplar. Miriam Creaser (2013) supports this figure and suggests that after oral contraception became widely available, local delivery rates dropped to around 4 births per month by 1963.

Despite the social changes and medical advancements that have transformed childbirth since the 1950s, many aspects of Call the Midwife are recognisable to a modern audience. It doesn’t shy away from unpleasant bodily functions and includes graphic yet realistic birthing scenes. A normal labour is shown progressing through stages – with waters breaking, contractions spaced 5 minutes apart, “crowning” (when the top of the baby’s head becomes visible), delivery of the afterbirth, and clamping of the umbilical cord.

It shows how in many ways the management of maternal health remain unchanged. Breathing slowly and deeply is a technique contemporary midwives instruct their patients to use (Rhodes, 1999). The Pinard horn, used in multiple scenes to monitor the heartbeat of the foetus, is a medical tool still widely used in obstetrics today (Rhodes, 1999). Creaser (2103) identifies that the mother who goes against against medical advice to keep her premature baby at home rather than sending it to the hospital is essentially using an early form of “kangaroo care”. By keeping him close to her skin and feeing him breast milk from a dropper, he manages to put on weight. The nurse is delighted because just as it is today, breastfeeding babies to improve their weight gain was recognised in the 1950s as important in the treatment of pre-term babies.

Although technology may have improved since the period that the programme is set, the essential approaches to diagnosis and treatment are little changed. Jenny explains that swollen ankles are a symptom of pre-eclampsia and uses a basic diagnostic test to check for signs of protein in the urine by heating a test tube over a Bunsen burner. A mother who undergoes extensive bleeding and goes into shock after labour is given a blood transfusion and antibiotics (Rhodes, 1999). A woman with a syphilitic chancre is treated with an injection of penicillin in the same manner used to treat primary stage syphilis in the present (Rhodes, 1999). Her husband is also treated in an example of the “contact tracing” still used in the management of STIs (Rhodes, 1999).

Overall, Call the Midwife presents an accurate portrayal of midwifery during the 1950s in a format that makes for informative and enjoyable viewing. Watching just a single episode provided a wealth of information about experiences of childbirth in the past that are partly relevant today. Well written and with commanding performances from the cast, the series does not appear to sacrifice scientific facts or detail for dramatic tension.

Have you seen Call the Midwife? Feel free to leave a comment below.

References

Creaser, M. (2013). Call the midwife: a true story of the East End in the 1950s. Infant Observation: International Journal of Infant Observation and Its Applications, 16(3), 286-289.

Rhodes, M. (1999). “You worked on your own, making your own decisions and coping on your own”: midwifery knowledge, practice and independence in the workplace in Britain, 1936 to the early 1950s. Dynamis, 19, 119-214.