Thalidomide Scientific Component:
Molecular Mass: 258.23 Da
Color: white crystalline
Melting point: 271°C.
Insoluble in ether and benzene
Has a low solubility in water, methanol, ethanol and glacial acetic acid”
All bulleted sources from (Erkoc, 2004)
Thalidomide is composed of two rings with each of the rings having different chemical makeups (Franks, et al, 2004). The left-hand side ring is thought to be the ring responsible for the teratogenic effects seen (Franks, et al, 2004). The right-hand side ring has a structure very similar to hypnotic drugs and the sedative properties of the molecule are thought to arise from this ring (Franks, et al, 2004). This molecule is known to exist in two optical forms, which are mirror images of each other. One of the forms is thought to be responsible for the therapeutic effects of thalidomide and the other is thought to be responsible for the teratogenic effects. It is believed that the thalidomide tragedy occurred because the isomer ‘flicks’ between the two forms.
Thalidomide is a designed drug that first appeared and produced in Germany in the late 1950s. It was, at that time, the principal drug used to treat headaches, insomnia, and morning sickness in pregnant women. It was known for its non-toxicity and uncomplicated side effects, such as inducing longer periods of sleep in the women. The drug was on the market for four years, however, after it was found that it has teratogenic effects and was withdrawn from the market in 1961. Babies of mothers who had taken the drug during pregnancy were born with complicated birth defects.
The Adverse Reaction:
Most women took thalidomide in the first three months of pregnancy, when the babies limbs are beginning to form. One of the most devastating complications of thalidomide is phocomelia – the absence of most of the arm. Limbs malformations can consist of missing parts of the limb such as fingers or toes. Limbs can also be deformed in such a way that they do not match the rest of the body. Sometimes babies would be born with extra fingers or toes, and/or paralyzed limbs.
Thalidomide-exposed babies would be born with second most common defects, which included ear and eye defects. The outside part of the ear would be small or missing, and cysts would have developed on the eye’s surface. Also, missing or small eyes can be related to the drug complications. Moreover, facial muscles would be weak and crack lip can occur.
Kidneys, heart, urinary, and intestine malformation could also present in babies of mothers who had prolonged Thalidomide usage during pregnancy. Mental retardation presents in babies exposed to Thalidomide.
How Did The Society Respond?
After the introduction of thalidomide as a pharmaceutical, there was a huge increase in birth defects, especially in Europe and Canada (FDA). In 1961, a German pediatrician, Adkind Linz, was doing his usual routine in his clinic when a mother presented with her newborn baby. The child was suffering from a very rare case of fetal abnormalities with atrophied parts. He was born without legs and without other limbs. The doctor regretted this baby’s rare situation and he was shocked by the occurrence of such a very rare case. He did not know that within ten days he would meet, in the clinic, another case of a newborn baby suffering from the same problem. The Doctor was certain that the recurrence of this very rare case within ten days couldn’t be a coincidence.
The doctor subjected the cases to a research study, recalling all the circumstances experienced by the two cases before birth in search of a common factor between them. After the search, he did not find a common known factor that could be a cause of such a birth defect, but he noticed that both ladies participated in the use of a new promoted drug at the time called (thalidomide).
This Figure shows the UV absorption at 300
mn of Thalidomide within one hour and
24 hours after it was dissolved and diluted
in DMSO or in acid saline.
In The U.S:
When it was introduced in the 1950’s, drugs containing thalidomide were widely used and marketed as safe in places around the world including Europe, Australia, Japan and Canada (Franks, et al, 2004). However, the United States Food and Drug Administration (FDA) did not approve Thalidomide until 1998.
Frances Kelsy, a physician and a pharmacologist who was just starting her career at the FDA when a new drug that was causing unusual deaths at that time was highlighted. Frances was one of the young physicians who worked for the FDA. She was assigned to review another drug (thalidomide) as a painkiller, to determine whether it would be safe to be prescribed for pregnant women to alleviate morning sickness. Thalidomide was already approved to sell in Canada’s market and more than 20 European countries, but Frances refused to approve it and requested further studies. While the thalidomide manufacturing company was putting so much pressure on her to get the drug approved, Kelsy continued to withhold approval; the manufacturers tried everything they could to get around her judgment.
In November 1961, news began to come to light in Germany and the United Kingdom that mothers who had used thalidomide during pregnancy were now having children with acute birth defects. Dr. Helen Taussig heard about the tragedy from one of her students and went to Europe to investigate. Tauusig was able to assist Kelsey disallow thalidomide in the United States for good. At least 4000 children in Europe were affected by the drug, but thanks to Kelsey’s scrupulous professionalism a similar heartbreak was averted here in America.
On August 7, 1962, President John F. Kennedy awarded Frances Kelsey the top honor given to a civilian in the United States, the President’s Award for Distinguished Federal Civilian Service. She was the second woman to ever obtain the award. Kennedy acknowledged, “Her exceptional judgment in evaluating a new drug for safety for human use has prevented a major tragedy of birth deformities in the United States. Through high
ability and steadfast confidence in her professional decision she has made an outstanding contribution to the protection of the health of the American people”. Kelsey helped structure and implement amendments to FDA drug regulation laws to institutionalize safety measures of the patient in drug investigations. These regulations required that drugs be shown to be both nontoxic, safe and efficient, that informed approval is obtained from patients when used in clinical trials, and that adverse reactions be reported to the FDA.
Grünenthal Group and Thalidomide Agency UK:
Thalidomide was created by a German company (Grünenthal) in 1953 and was used in the late 1950s and early 1960s as a “wonder drug” to treat morning sickness, headaches, coughs, insomnia and colds. Grünenthal, and after the tragedy, they expressed their regrets to the victims of the Thalidomide tragedy. However, the victims rejected the company’s first apology stating that regret is not enough. Moreover, the thalidomide agency UK hat represented the victims of the tragedy dismissed the apology and they considered it inadequate.
As a matter of fact, before the company launched the drug they tested the effectiveness of its substance on specific animals, (in vitro), in agreement with standard pharmaceutical industry practices at the time. Later, when Thalidomide was launched in October 1957, however, there were no pharmaceutical legislations in the Federal Republic of Germany. As a result, in October 1959 two different side effects were reported. Two years later and after some investigation, the company suggested that the drug shouldn’t be available over-the-counter drug and but other than that should be only prescribed by the physician. Six months later, pediatricians noticed the increase of number of babies who were born with similar birth defects to the mothers who used Thalidomide during pregnancy. Then, the doctors forced the company to remove the product from the market, and within twelve days the product was withdrawn.
Grünenthal case was raised in court and nine of the Grünenthal executives and research employees were the defendants. Legal trial was associated against senior manager from May 1968 until December 1970. The intention of the trial was to find out whom to accuse for the tragedy. Then the trial was closed and the judgment were appearing to minor fault on the part of the defendants. It didn’t find that the defendants had acted inaccurately in dealing with the risky neurological effects caused by the product.
What Should We Do Differently?
It is to be assumed, in this section, that one of us is a project manger in a company that produces such a dreadful drug. Before making a consideration of this issue, it is important to consider the time in which these events happened. In other word, if that was the case half a century ago, I’m certain that I would think differently. In the sixties the fact of designing a drug wasn’t as easy as these days and the legal procedures wasn’t that tough. For example, to invent a drug there are three important factors that should be considered, time, money, and scope. The time wasn’t an issue half a century ago. The challenge was to spend less money, less time and to produce more of a certain product. Also, Competing with other companies was considerable to get the most of the fame for the company to sell their products in the market. So, if I had to put myself in that company’s shoes, I would actually insist to get more research done on a variety of animals, not only a certain type as they’ve done. I would, also, extend the period over which these experiments were conducted. What Frances Kelsy did do was brilliant, however. She didn’t approve the drug even though she was putting herself under the risk of getting fired from the FDA.
Talking about the FDA, if I was a project manger at the FDA and I was assigned to a similar case I would do exactly what Kelsy have done. In fact, putting people’s life under the risk of such a drug is horrible. A project manger main aim in a drug company is primarily to help in producing drugs that would cure people from diseases and help them to get healthy and risk-free life. Of course getting the maximal profit is important, but its only if the safety and efficiency is the priority.
“My importance to the world is relatively small. On the other hand, my importance to myself is tremendous. I am all I have to work with, to play with, to suffer and to enjoy. It is not the eyes of others that I am wary of, but of my own. I do not intend to let myself down more than I can possibly help, and I find that the fewer illusions I have about myself or the world around me, the better company I am for myself.” Coward, Noel
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3. National Toxicology Program; http://ntp.niehs.nih.gov/go/project
4. U.S. Food and Drug Administration & http://www.fda.gov/cder/news/thalidomide.htm
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