(10d) Thalidomide - And the apology that angered its victims

Thalidomide (tradename Softenon), a drug known all over the world for the terrible birth defects it caused including shortened arms and legs (the best known side effect as this is very visible, see figure, taken, then slightly edited, from Langman's medische embryologie, 10de herziene druk by T.W. Sadler), blindness, deafness, heart problems and brain damage while many children died because of the drug. I write this article in response to an article published on the BBC-website.

Extreme example of limb deformities.
Thalidomide was invented in 1953 by the German pharmaceutical company Grünenthal. The drug was launched by the company in 1957. By 1961, the Australian doctor William McBride reported that an increased number of deformed babies were born at his hospital to mothers who had taken thalidomide; the same year, Softenon was taken from the market.

Now, almost 50 years later the company Grünenthal finally apologised for the problems the drug they invented caused to children who still suffer as adults. The CEO, Mr Stock, also apologised it took the company so long to apologise but he claims the reason for this was "as a sign of the shock that your fate caused in us". He also said "We wish that the thalidomide tragedy had never happened" and that the company regretted that the potential for thalidomide to affect the development of foetuses "could not be detected by the tests that we and others carried out before it was marketed". However, some victims are unimpressed with the apologies and demand compensations as they suffer from the effects of the drug.

I understand the anger of the victims. Indeed, having one or more of the above described problems is terrible, not only because the effects limit the career possibilities of the affected, but they also cause suffering up to these days. Therefore, if the company is sincere in their apology, it should help the patients with their treatments. It seems companies involved in the production and distribution of the drug already paid in the past and still do. E.g. the BBC article informs us that UK manufacturer Diageo pays since 2005 about £6.5m a year, a doubling of what they paid before. Also Grünenthal paid in the past compensation to victims. And now there is also the apology.

For some victims the apology is not enough and much too late. However, new leaders can't restore the silence of past leaders and thus should not be blamed they only now apologise, at least they apologise for past mistakes. But, many victims want to see more compensations as proof the apology is sincere.

Although the company says it didn't know at that time the effects of the drug on the development of foetuses, Mr Martin Johnson, director of the Thalidomide Trust, told the BBC the manufacturers were still trying to continue the myth that no-one could have known of the harm the drug could cause when there was, he said, much evidence that they did know.

Of course, the statement from Mr Johnson is very serious, and he should show evidence of what he claims. Because if the researchers and company knew about the potential harm, then the company should be forced to pay heavy fines and those who knew should be sentenced. To proof Mr Johnson is wrong and the sincerity of the apology, the company could publish on the internet all the related files. In doing so, all victims and those who are interested will be able to read for themselves what the company knew before releasing the drug. It would also be interesting for science writers to learn how mistakes can be avoided in future. Of course, if the files show the company didn't know about the toxicity, some people may still claim not all documents are published. Nevertheless, the company should publish so the people can judge for themselves and stop thinking the company has something to hide because when people think a pharmaceutical company can't be trusted it may damage the reputation of the pharmaceutical industry as a whole.

I think Mr Stock is tellin the truth when he says they were in a shock when these things happened (to make things more complicated, the inventor was a former Nazi party member and thus questionable). I believe (until the opposite is proven) the company was in good faith as they withdrew the drug the same year the birth defects were linked to the drug. If they were not honest, they would have tried to minimise the effects and sell the drug longer (publication of the files will reveal this). What would be the advantage for the company to sell a drug when they knew it would result in serious birth defects? Which company wants to harm its customers? I think people are wrong when they say companies only think about profit and shareholders although some do. Because most researchers and doctors go into the medical business first and foremost to cure people from illnesses; it is their bonus when they can defeat a disease, it increases their status. Therefore, researchers will normally not sell drugs that damage because that will destroy their reputation and thus career. Unless they are criminals who sell illegal drugs but those people will hide their business and have not much of a reputation, except money. Also business people have to think about profits and thus should not have the final decision about releasing drugs.

The company says the potential of the drug to damage foetuses could not be detected at that time. Indeed, it took many more years before scientists started to understand the mechanisms why things went wrong while there are now more and better techniques available. Because of the terrible side effects caused by thalidomide, new laws were passed requiring safety testing on pregnant animals (from different species) before a drug can be sold. Up to that moment these tests were less strict as not many expected at that time that drugs could damage the foetus so badly (and we are still discovering more about their effects).

Many years earlier, another disaster, the Elixir Sulfanilamide disaster in 1937 happened before people realised stricter tests were needed to protect the public and thus the American Congress passed the Food, Drug, and Cosmetic Act in 1938, soon followed in other countries. The Act forced companies to perform animal safety tests on their proposed new drugs and submit the data to the FDA before being allowed to market their products. You see, only from 1938 onwards the toxicity of drugs are tested systematically on animals, something we now find only normal. Or do we?

Indeed, many animal right groups no longer want that new drugs are tested on animals. I agree with these groups that:
  1. animals should be treated as humane as possible in order to maximise their comfort and reduce their suffering and
  2. the smallest possible number of animals should be used to get an answer to essential questions.
But the above examples demonstrate that not testing the safety of drugs on animals can be very dangerous and although the toxicity of drugs can be tested to some extend in-vitro, animal research remains important to test the effects of drugs on the body as this will give additional information compared with tests on cell cultures (e.g. drugs may be protected from elimination (= biotransformation and excretion) by binding to proteins (e.g. albumin) which are not present in cell cultures and thus the drug behaves differently). But scientists continue their research to find reliable alternatives for animal studies.

Unfortunately, in 2006 we learned that animal testing is not always exclusive. In the UK, six young men became critically ill during a clinical drugs trial but survived. The company claimed all procedures were followed before starting the clinical trial. Everyone involved was shocked: the victims and their families; the people working for the pharmaceutical companies as many years of research to cure an illness were in vain but also other scientists and health regulators because it seemed things still can go wrong. The UK's Medicines and Healthcare products Regulatory Agency (MHRA) started an investigation to understand what went wrong in order to be able to avoid this happening again. That doesn't mean we should stop clinical tests as mostly they go well but we have to improve them even further. We should also be grateful some people take the risk of testing the safety of newly discovered drugs.

Are we maybe getting too scared to allow drugs to be used? Of course, after the above mentioned errors, it is normal that stricter safety rules are made. It is very understandable victims are angry and they should be able to know what went wrong and who was responsible. They should be able to go to court where independent experts can make a judgement. But errors can always happen, e.g. maybe some people are allergic to a drug; therefore leaflets warn doctors and patients about this risk to reduce it happening. Drugs can get a bad name because some people misuse them. The incorrect use of medicines should be prevented without banning the drugs or people will buy them illegally while the dangers of misuse should be clearly explained. Some people make money from going to court over so-called errors, making healthcare insurances almost unpayable. The biggest problem are people who are against drugs and more generally against sciences; they use errors to discredit the pharmaceutical industry in the hope people will turn against them. Then scientists should unite and explain people about the advantages of science. E.g. vaccines save people from diseases but sometimes something can go wrong (side effects are possible) and thus there is always a danger, but because the danger is known it is smaller then the risk of the disease. Thus scientists should be open so people know scientists do everything possible to prevent mistakes.

The Guardian (25/08/2012) published an article about children suffering from neuroblastoma, a cancer and the biggest child-killer after accidents. It seems there is a three-drug treatment in the USA that, according to a publication in a medical journal, cuts deaths by 25% although European regulators are still assessing the efficacy of the drugs. Of course, we have to be sure the drug works and is save, but some parents are so desperate to save the life of their child that they go outside Europe for treatment. When there is no approved cure for a deadly disease, maybe more patients should be allowed to use a test drug when there is some evidence the drug may heal, and then researchers can follow the response very closely and react whenever necessary. Of course, the persons involved should be fully informed, also about the possible dangers and should sign a document they understand the risks. But then, when something goes wrong, some people may still blame the medical profession and thus the profession may become even more careful. Thus one can see the problems health workers are facing in these circumstances while they try to make the best decision for their patients. In the case of the bubble boys, new techniques were tried and while it worked for some children, others died. There is also an advantage of doing clinical studies in a number of different countries because larger numbers of people are studied and thus it is more likely possible side effects show up although that doesn't mean each country has to perform its own studies when studies in many other countries demonstrate the drug is effective and safe.

In conclusion, thalidomide caused terrible side effects and people are still suffering and thus I understand they are angry and demand financial help. But I also think the victims should accept the apology as it shows they are not yet forgotten (although to be honest, I can't be sure how I would react) on condition the company is open about what happened and pay some contribution. Other pharmaceutical companies may also pay towards a fund to help people who suffer from medical mistakes as possible accidents at their companies were prevented because of what they know what can happen. Indeed, scientists learned from the errors and stricter regulation was introduced while they improved safety tests. These tests are not only performed in pharmaceutical companies but also at independent universities where scientists publish their results in peer-reviewed scientific journals, available for everyone who is interested. Finally the test results are evaluated by medical control agencies who approve or reject the marketing of drugs. During the marketing, companies have to publish leaflets mentioning all side effects and inform who can or cannot use the drug. Even post marketing, the public and doctors can inform the control agencies and industry about possible new side effects and thus the safety and efficacy of the drugs are continuously monitored.

Scientists try to be as open as they can, if not by heart than because laws and control agencies force them to be open to the public about their products. This also shows the importance of government control, adjusting laws to new situations and verifying the laws are followed. And while a drug can be toxic, sometimes it may help other people: thalidomide is now tested in patients with multiple myeloma, an incurable bone marrow cancer.


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