Thalidomide and Conspiracies

July 27th, 2006 by Ben Goldacre in bad science, MMR | 29 Comments »

i was speaking at an investigative journalism course last weekend and someone on the course (someone a bit rabid as it happens, especially about MMR, rather disappointingly) was suggesting that thalidomide was another example of the medical profession covering stuff up.

now, this is something people often say, but as i understand it, the whole thing was managed fairly swiftly and appropriately (it could never be swiftly enough, but you know what i mean): that australian doctor mcbride wrote to the lancet with his hunch on thalidomide, people were then aware of the problem so they looked into it, found it was causing birth defects, then pretty quickly it was off the market, and the yellow card system was launched in its wake.

the great investigative journalist philip knightley even talks in one of his books about how bad he felt that the sunday times insight team and the journalistic profession as a whole had been a bit slow off the mark with thalidomide, but the scandal i think they were writing about was whether the drug company would cough up damages or not, not that the medical profession covered up the side effects and made mcbride a pariah, as i have been told a few times.

anyway, this is proving to be a bugger of a question to settle on the internet, so does anyone here remember what happened, or have an inside track? were doctors who spoke out on thalidomide bullied? was there a cover up by the entire medical profession? i know some of you are, like, famous doctors and scientists and everything.

weirdly, mcbride was censured – but many years later – for hokey research. maybe thats what people think is the conspiracy? is there any reason to believe that was a conspiracy?

looking forward to your thoughts/recollections, here or in email if you’re shy. ideally the shift button will work on your keyboards.


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29 Responses



  1. coracle said,

    July 27, 2006 at 3:38 pm

    I can’t help much. It was launched, I believe, in 1956 and withdrawn 1961. Part of the problem was that it was tested on rats and mice, which don’t suffer the teratogenic effects. Subsequent to this, develpomental testing uses rabbits (also guinea pigs maybe, not sure).

    I don’t see much conspiracy there, just insufficient knowledge.

  2. Symball said,

    July 27, 2006 at 4:09 pm

    It is used as an example of one of the main triggers for the introduction of GLP regulations and the current testing regime we have in place for new products. Because of its notoriety many ‘anti’s’ use it as a reason for not testing instead of its real significance which was the realisation that a more rigorous testing regime was required.

  3. Ben Goldacre said,

    July 27, 2006 at 4:33 pm

    i guess the question is: some people claim there was a large scale wrongheaded dismissal of the thalidomide problem by doctors, which they feel somehow parallels MMR today. is this true? was thalidomide covered up by doctors? did they dismiss concerns? did doctors bully other doctors who spoke out, and make them pariahs?

  4. Dr Aust said,

    July 27, 2006 at 4:39 pm

    The only detailed account I have ever read was in a book called “Medicine’s Greatest Mistakes” (!).. so not 100% sure of the accuracy… also seen various TV docs about it.

    As I recall the German company that invented it was perhaps a bit secretive about their test data, but it is pretty clear that there was NO testing on pregnant animals at all prior to the drug being used on pregnant women, because none was required for regulatory approval – this would go along with your “regulatory regime” comment.

    The Research Defence Society has a page on thalidomide which gives some refs:

    www.rds-online.org.uk/pages/page.asp?i_ToolbarID=5&i_PageID=1070

    Inerestingly, thalidomide didn’t get licenced in the US because the FDA (or equivalent) official handling it felt the test data weren’t good enough – so the kids with phocomelia were mostly in the UK, Europe (?), and in places of British ex-dominion.

    The same book gave an account of the later (80s) exposure of McBride for iffy research in connection with a different drug, bendectin (Debendox) which as I read it was quite clear-cut. So McBride was a tragic figure in the end; he was lionized in Australia after the thalidomide business, and ended up with his own research institute; but a bunch of years later he tried to repeat his greatest moment by faking animal data on debendox and was eventually disgraced (and struck off by the Australian Medical Assocn). In that case the “whistleblowers” who exposed him were first sacked and then widely disbelieved before they found a medically-qualified journalist who listened to them, as I have heard the story.

  5. Dr Aust said,

    July 27, 2006 at 6:52 pm

    Here is an interesting article on the FDA’s website about Frances Kelsey, the official who insisted the regulatory data on thalidomide was not good enough for approval in the US:

    www.fda.gov/Fdac/features/2001/201_kelsey.html

    There seems to be little suggestion in the articles I have looked at that it was “the medical profession” that was covering up – most of the opprobium gets directed at Chemie Grunenthal, the German company that marketed the drug for morning sickness. As I have read the histories, the doctors may have been guilty of a measure of over-enthusiasm in handing out the drug, but that is basically a verdict of 21st century hindsight .

    Thalidomide was heavily marketed as being safe, particularly as it was “impossible to overdose” – taking too much produced somnolence in the mother but nothing worse (!), so the drug was touted as the “wonder product” that mothers in the first trimester with persistent morning sickness had been waiting for.

    Grunenthal is portrayed in some stories as refusing to do more tests once worries about the drug arose (these suspicions were mostly about it producing optic neuritis), and opposing taking the drug off the market once the evidence of birth defects had come out (the German authorities ignored them). Richardson-Merrill (the US company that licenced the drug) apparently lobbied hard to get it approved in the US, according to the profile of Kelsey.

    Anyway, the received version of the story that has come down is mostly along the lines of inadequate pre-approval testing and cavalier profit-driven early pharmaceutical companies.

    The thalidomide scandal is widely credited with being instrumental in getting the US Govt to pass laws (in 1962) which, for the first time, required manufacturers to show that drugs were EFFECTIVE in order to get approval. Prior to that they only needed to show the drugs were safe to get FDA approval…bit like “supplements” in the UK today?

  6. mushyp said,

    July 27, 2006 at 6:57 pm

    @coracle: As an organic chemist, I was always told that of the two enantiomers (mirror images) of thalidomide, one possesses genuine anti-nausea properties, and this was the version which was tested in clinical trials, and found to work as desired.

    When it came to scaling up the manufacture, less care was taken in only manufacturing the one enantiomer, and the drug that ended up on the shelf was a racemic mixture — an equal mixture of both mirror image versions. One enantiomer worked as tested — reducing morning sickness — and the other enantiomer served to arrest the growth of blood vessels, with the resulting birth defects.

    Is this the case, or have I been lied to by The Man?

  7. pv said,

    July 27, 2006 at 7:40 pm

    I know my comment here isn’t scientific (what’s new?), but isn’t it just too easy to condemn the time lapse between every discovery of an error and its resolution as a conspiracy? Especially medical errors and those made by “establishment” agencies/representatives. Shouldn’t the onus be on the accusers to come up with something approaching incontrovertible evidence, rather than just a motive. Any idiot can think of motives by the score – saving one’s skin is the usual number one “motive”. Conspiracy theorists, of which there are far to many and who are far too tedious for words, really ought to get out more often. I have a theory that conspiracy theorists indulge in their fantasies to draw attention away from the boring truth that their lives are monotonously dull and empty.

  8. superburger said,

    July 27, 2006 at 8:08 pm

    mushyp, it’s true that thalidomide is / was supplied as a racemate, and only one enantiomer is a teratogen, however, it makes no difference as when the drug enters the body it racemises rapidly enough to still cause birth defects.

    How it was established that one enatiomer was the teratogen and the other safe was never made clear to me. Perhaps modelling the binding of R- and S- thalidomide onto DNA?

  9. Dr Aust said,

    July 27, 2006 at 8:09 pm

    HI MushyP,

    I have seen this story in several places too, and it is widely used to make optical isomerism interesting…..but I think it is a probably a red herring. There were some early papers claiming this, but it is now believed that the enantiomers can interconvert in solution at physiological pH, so the earlier experimental work giving selective enantiomers to animals (in the mid- to late 60s) was misleading

  10. crgn said,

    July 27, 2006 at 8:41 pm

    I think the Sunday Times story was that Distillers (who produced the drug under licence) was quietly settling out of court and the Sunday Times’ angle was that they were doing it to avoid bad publicity. The 1979 ECHR ruling is here. I think the gist of it is that the ST wanted to publish an article which became the subject of an injunction based on the fact that it might constitute contempt. From what I can work out (I don’t have my legal head on right now), the ECHR ruling came in 1979, which meant it was seven years between the original injuction and the time anyone could even discuss the matter in the media without risking a court case of their own.
    Not a cover-up, then, more a legal filibuster.

  11. mushyp said,

    July 27, 2006 at 9:23 pm

    Dr Aust – I sense that you find optical isomerism less than 100% fascinating. Heresy. I’ve never heard anything so inflammatory :-)

    Thanks to you and superburger for setting the record straight.

    And balls to The Man.

  12. crichmond said,

    July 27, 2006 at 10:31 pm

    William McBride showed that thalidomide caused birth deformities.
    He was, rightly, lionised.
    Some years later he ran an unfounded campaign against bendectin and it was banned around the world, thus permanently depriving pregnant women of a safe and effective treatment.. The subject is splendidly covered in a book called Galileo’s revenge: Junk Science in the Courtroom, by Peter Huber (HarperCollins 1991). It is also covered well, (as I recall from memory) in Iain Chalmers’s Effective Care in Pregnancy and Childbirth.

  13. Ben Goldacre said,

    July 27, 2006 at 10:46 pm

    cool, i just got Galileo’s Revenge off abe. it came from kingston, jamaica, which felt nice. you’ve got to love how the interweb brings a whole new flavour of second hand serendipity.

    anyway, are we basically saying that anyone claiming thalidomide was a medical profession cover up is talking nonsense?

  14. Filias Cupio said,

    July 27, 2006 at 11:19 pm

    There’s a book/series of articles/series of TV documentaries in here. Take half a dozen prominent drug/disease controversies, three real and three false alarms. Look at who the whistle-blowers were, how they were treated, how the issue gained publicity, the reactions of involved parties, who was right and who was wrong. One chapter/article/program per controversy, and a final episode on the lessons learnt: how can we decide who to trust in future controversies? How should public health bodies respond, before there is certainty about the merits of the case?

    For the real health problems, thalidomide and BSE/JKD leap to mind. Other possibilities are the early stage of the AIDS epidemic, the recent drug trial near disaster, or any recent major drug recall.

    For false health problems: MMR, polio vaccine (false rumours about the vaccine caused an outbreak in parts of Africa a few years ago), the McBride beat-up mentioned above.

  15. John A said,

    July 27, 2006 at 11:30 pm

    Just to be explicit on coracle’s point:
    “it was tested on rats and mice, which don’t suffer the teratogenic effects”

    They do. But it was just never tested on pregnant animals.
    (references on the RDS Website already posted)

  16. Art West said,

    July 28, 2006 at 3:22 am

    I have always been told by my mother that she asked the family doctor about taking thalidomide when she was pregnant with me. He told her that he had doubts about thalidomide and dissuaded her. Given that I was born in early April 1957, he seems to have had doubts extremely early. Of course, it could have been a lucky hunch, but if he had any real knowledge, however vague, on which to base his opinion then that information was probably pretty widespread to have reached a small town Midlands GP.
    In any case, I’m grateful that he, for whatever reason, held that opinion as I went to school with numerous kids who were severely disabled by thalidomide.

  17. coracle said,

    July 28, 2006 at 7:51 am

    JohnA, My mistake, thanks for the correction.

  18. sockatume said,

    July 28, 2006 at 8:15 am

    I may be barking up the wrong tree here, but hasn’t thalidomide come back on the market as a general anti-nausea medicine (obviously one counterindicated for women who are pregnant or trying to have children)?

  19. mushyp said,

    July 28, 2006 at 8:42 am

    @sockatume – I’m pretty sure that it’s currently on the market being used for cancer treatment, because the cause of the birth defects — restriction of blood vessel growth — is a really useful property to arrest tumour development.

  20. MikeTheGoat said,

    July 28, 2006 at 9:00 am

    It’s also used to treat a complication of leprosy.

  21. A Reader said,

    July 28, 2006 at 10:40 am

    This turned up in an academic search. Unfortunately my institution doesn’t have access to a full copy, but you can buy the individual article online, if you think it looks any use.

    A Tale of Two Experts: Thalidomide and Political Engagement in the United States and West Germany

    Author: Daemmrich A.1

    Source: Social History of Medicine, Volume 15, Number 1, April 2002, pp. 137-158(22)

    Publisher: Oxford University Press

    Abstract

    The physicians, Widukind Lenz and Frances Kelsey, played crucial roles in the thalidomide drama of the early 1960s. Widespread use of the drug in West Germany was only halted when the paediatrician, Lenz, publicized its association with the birth of nearly 4,000 children exhibiting abnormal limb growth. Few cases were reported in the United States because Kelsey, a medical officer at the US Food and Drug Administration, repeatedly delayed thalidomide’s marketing approval. Experts in both countries were expected to demonstrate publicly the professional ‘objectivity’ of medicine and the institutional ‘disinterestedness’ of regulatory bodies. These norms were invoked both by industry representatives seeking to undermine the two experts and by critics desiring stronger regulatory controls. Comparing Lenz with Kelsey demonstrates how institutional structures shape an expert’s social and scientific roles. While the United States provided important protection from external pressure for Kelsey through her regulatory position at the FDA, Lenz was open to sharp criticism, especially when giving expert testimony during a lengthy court trial. The degree of exposure to politically motivated attacks differed for these two experts; they nevertheless faced similar threats to their professional credibility and personal integrity when they publicized links between thalidomide and birth defects.

  22. coracle said,

    July 28, 2006 at 12:19 pm

    The rehabilitation of thalidomide has always amazed me. In combination with dexamethasone it’s now treatment of choice for multiple myeloma, I seem to remember a documentary some years ago about its use in untreatable ulcers.

    I believe it has an anti-TNF mode of action which I think is the presumed mode of action for its anti tumour activities.

    I’ve taken a quick look at the social history of medicine paper, I don’t think it’s massively useful. It’s short on details of the testing that it went through and focuses on the regulatory responses since the exposure of its teratogenic effects.

  23. poohbear said,

    July 28, 2006 at 2:21 pm

    Just heard reports on local news that American manufaxcturer has increased price of thalidomide to BC Cancer Institute, which was using it in the treatment of certain forms of cancer from about $30 per month to about $1,000 per month per patient. This is bloody ridiculous for a drug that has been around for 50 years, and pure profiteering on the part of the drug company. Not sure which one it is.

  24. Dr Aust said,

    July 28, 2006 at 4:06 pm

    Mushy P wrote: “Dr Aust – I sense that you find optical isomerism less than 100% fascinating. Heresy. I’ve never heard anything so inflammatory”

    – Have to ‘fess up on optical isomerism – it was the ludicrous way they had THREE different systems for classifying it that got me. (dl, DL and RS)… I have to admit to a B.Sc. degree in Chemistry but always prefered (bio)organic and transition metal chemistry. Although in my career in biomedical research it is the physical chemistry I (reluctantly) studied that has proved the most useful… another of life’s little ironies.

    —————————————————————

    Art West wrote (re doctors knowledge anbout the stuff in the late 50s) “Of course, it could have been a lucky hunch, but if he had any real knowledge, however vague, on which to base his opinion then that information was probably pretty widespread to have reached a small town Midlands GP.”

    – I would suspect it was because the drug was very experimental in 56-57, plus the dictum “don’t mess with what you don’t understand”, i.e. a 50s doc would probably know that loads MUST be going on in the first three months of pregnancy, but would also know the details of the underlying processes were pretty much a mystery. To give a powerful drug during that period if not absolutely needed would seem like a needless risk (it is quite interesting that the modern medical view of early pregnancy, based on a lot more knowledge, seems prett y much to bear out this piece of ancient wisdom). I was also born in the thalidomide era, though rather later, and my mother said she refused the drug for just this reason when the doctor suggested it for morning sickness.

    ——————————————————

    Coracle wrote:

    “The rehabilitation of thalidomide has always amazed me. In combination with dexamethasone it’s now treatment of choice for multiple myeloma, I seem to remember a documentary some years ago about its use in untreatable ulcers.

    I believe it has an anti-TNF mode of action which I think is the presumed mode of action for its anti tumour activities”

    – It seems to do a bunch of things, anti-angiogenic actions, anti-cytokine, modulating cell adhesion etc. It intercalates into DNA at lots of sites, though NOT randomly, probably accounting for the widespread effects.

    My reading was that treating leprosy (or “Hansen’s Disease” as the Yanks rather confusingly call it) was the major modern use, but it has been tried for a lot of other stuff, as mentioned by others here. Some kinds of Lupus (SLE) is another example.

    Of course, re-use of it has sadly led in some places (e.g. Brazil) to MORE birth defects, as the stuff is so potent in its teratogenic effects that doctors AND patients have to be INCREDIBLY careful with it. One dose at the “wrong” time in early pregnancy is enough to cause tragic consequences, and it gets to all sort of places in the body. For instance, if a man takes thalidomide it the stuff can be detected in his ejaculate (strange but true) – so potentially it could affect any woman who he gets pregnant. In the US when the FDA re-licenced it they passed special rules about its use to try and avoid more childhood deformities.

  25. monkeychicken said,

    July 29, 2006 at 12:36 pm

    From fact to fiction:

    One of the stories running through Irvine Welsh’s book “Ecstacy” (not the one that is being turned into a film) strongly echoes what happened with thalidomide. The story portrays the “scientists” as knowing that the drug would cause birth defects and were paid off by the drug company. It is possible ths story has entered pop culture and could have been mixed up with the real truth (whatever that is).

  26. Robert Carnegie said,

    July 29, 2006 at 8:07 pm

    Re rehabilitation of thalidomide, well, arsenic, deadly nightshade, and rat poison are or have been prescribed to patients by doctors fully aware of the negative associations of these substances.

    Re “Widespread use of the drug in West Germany was only halted when the paediatrician, Lenz, publicized its association with the birth of nearly 4,000 children exhibiting abnormal limb growth” – I think “only” may be unfortunate. Obviously you’d continue using an evidently effective drug while there was no evidence of problems with it.

    I think the only-one-isomer-was-tested story is not sound – rather that they’d not really investigated the question of isomers. When they did, and found that one was the effective drug and one was the cause of side-effects, they got excited about it again until they found that each naturally turns into the other when used – which of course weakens (well, complicates) the story further if you wanted a simple demonstration of Why Isomers Matter, but you can probably gloss over the nasty fiddly bits, as long as you don’t leave them with the impression that the problem was solved.

    Another apparent mystery at one point, I think I recall, was a claim that people affected by their mother’s thalidomide use went on to to have children with similar disabilities. What came of that one? I’d guess genetics…

  27. FlammableFlower said,

    July 29, 2006 at 9:26 pm

    Just to through my oar in: I thought it was originally marketed as an anti-emetic, and then was “off-label” prescribed to pregnant women with morning sickness. There’s an article in this week’s New Scientist on the pros and cons of off-label perscribing. Can’t get hold of it at the moment, but it was about a drug designed for serious arrhythmia (spelling?) that became prescribed for much milder arrhythmia and was believed to cause 50,000+ unecessary deaths as it actually made things worse.

  28. BobP said,

    July 31, 2006 at 8:43 pm

    Hi, Ben –
    The actual events were a bit before my time. The Sunday Times was prevented by an injuction in 1972 from publishing an article criticising Distillers’ (the UK licence holder) handling of the affair and in particular the compensation offered to victims. After a number of appeals, the injunction was overturned in 1979 and they published the story. Via your contacts at the Guardian, do you have access to their archives?

  29. apothecary said,

    August 2, 2006 at 8:36 am

    Been enjoying the site for ages, first comment ventured

    Re Thalidomide, its popularity was in part due to concerns over the toxicity of barbiturates, which were widely used as sedatives at the time – overdoses of which are highly toxic and difficultt to manage – or at least that’s what the marketing said.

    I once worked in a hospital DI centre where we had some old promotional material for thalidomide from the time. There was a poster of a toddler with a bottle of mummy’s tablets, and the strapline was something to the effect that he could be in danger of a fatal barb OD, so the caring, responsible GP should prescribe thalidomide

    (presumably, the idea of using child-resistant containers and keeping meds out of sight and reach of children, or even that people didn’t really need the seadtive, hadn’t dawned on people).