This is the transcript for the third episode of our series on the history of UK drug use in the 1950s and 1960s: Thalidomide and the Profession and the Industry. It contains a good deal of additional information left out of the podcast.

References used can be found here

On the 22 June 1961 in Hamburg, a Northern German city on the Elbe, Doctor Widukind Lenz, the head of Hamburg’s children’s clinic, got a visit from a new farther Karl Schulte-Hillen. You see Karl seeked Dr Lenz out to investigate a condition that was plaguing his home town of Menden. Two months prior to this meeting, Karl’s wife Linde gave birth to their son, Jan Shulte-Hillen, and the sight of the child shocked him. The newborn's arms were malformed, short with missing fingers. “What’s with your husband? Has he got no arms?” a mid-wife had asked Linde upon seeing the child.

The fact Karl’s sister had recently given birth to a similarly malformed child did seem to point the fault at Karl, or at least his genetics. The events traumatized Karl. He would later state that, “For days I didn’t see people’s faces or bodies, all I saw was their hands.” However, Karl would learn that many more children in Menden had been born with malformedlimbs; one the day before Jan. Karl told Dr Lenz he suspected some geographical cause was cursing the newborns of his home town with these malformaties.

Initially, Dr Lenz did not put much stock in the father’s claims and geographic theory. However, upon contacting a Menden obstetrician he was surprised to find that many babies had been born with malformed limbs not only Menden, but also neighbouring towns of Beckum and Munster; all towns within 40 miles of each other. More worryingly, Lenz conducted a study in his town Hamburg of babies born with phocomelia—this condition where babies are born with malformed or missing limbs—and found that in 28 years only one child had been born with phocomelia. Eight such babies had been born in the last year alone. Now, Hamburg is 170 miles away from Menden. Lenz realised this wasn’t some local problem, Germany was in the midst of an epidemic.

However, Lenz still had no idea what was causing it.

My father and professor Lenz, they travelled Germany in their old Volkswagen. And they went from one small village to another and asked, 'Are there any small children with short legs or short arms born?' And those kids were hidden away at that time in the small villages. And he asked in restaurants and bars and at the local police office and everybody said, ‘No, not in our town’.  And the he showed a picture of me and said this is my boy and can I please repeat my question. And then they said, 'At the end of the road there has been a very sad incident.'

His big break would come on 11 November, almost four months since Karl had approached him. A mother of an armless baby girl told him she had taken a sedative, Contergan, during pregnancy and so had a friend who also gave birth to a sufferer of phocomelia. Lenz felt he was on to something and the next day wrote to a friend that he had a “hot lead”. After four days of further investigation, he felt sure. He wrote to the drug’s manufacturer, German pharmaceutical company Grunenthal, explaining the situation and imploring the company no to “wait for the strict scientific proof. I consider it necessary to withdraw the drug immediately from the market until its innocence in causing phocomelia is proved with certainty.”

Before we continue I think it's worth mentioning what this drug was and the role it played. Contergan was a trade name for the hypnotic and sedative Thalidomide, first marketed in Germany in 1957. Thalidomide was one of these new propriety or patented drugs trying to muscle in on the barbiturate market. As we discussed in the first episode, barbiturates were hugely popular but non-patented so anyone could make them. If a company could persuade doctors to prescribe their patented and expensive drug over barbiturates they stood to make a killing. The tactic thalidomide’s manufacturers used to promote their product was to frame it as the "safe" alternative. You see, one of the big problems with barbiturates was its high overdose rate. It was pretty much impossible to overdose on thalidomide. The marketers used this one aspect of the drug to frame thalidomide as the "safest sedative around".

For example here is a Thalidomide add that ran in the British Medical Journal in 1961. In the UK a company called Distillers had bought the rights to sell thalidomide there and did so under the name Distaval. The advert pictured a toddler getting into a medicine bottle, creating a sense of impending tragedy. In bold the add proclaims:

This child’s life may depend on the safety of ‘Distaval’.
Consider the possible outcome in a case such as this – had the bottle contained a conventional barbiturate. Year by year, the barbiturates claim a mounting toll of childhood victims. Yet today it is simple enough to prescribe a sedative and hypnotic which is both highly effective… and outstandingly safe. ‘Distaval’ (thalidomide) has been prescribed for nearly three years in this country, where the accidental poisoning rate is notoriously high; but there is no case on record in which even gross overdosage with Distaval has had harmful results. Depend on the safety of DISTAVAL.

This marketing tactic made thalidomide a very popular drug. Its perceived safety and the fact it combatted nausea led to doctors prescribing thalidomide to pregnant woman to combat morning sickness; a practice thalidomide’s manufacturers were all too happy to encourage. This was the drug that Dr Lenz was now accusing of leading to massive birth defects.

Unsurprisingly, Grunenthal reacted aggressively to this challenge to their marketing claims. Lenz would meet their representatives twice in November at the Health Ministry’s offices. Both times they attacked Lenz’s claims and threatened legal actions. The most they would concede to is placing a sticker on thalidomide’s box warning against its use in pregnancy. The government officials were unimpressed and told them to withdraw it voluntarily or risk it being banned.

Still, the pharmaceutical company stubbornly fought on. Even after they received a letter from the UK sellers essentially saying they had received reports that thalidomide might be causing deformities in babies.

Perhaps relevant to Grunenthal’s Director of Research and Development, Henrich Muckter’s, refusal to pull the drug from sale is that Muckter received a bonus of one per cent of some the company's drugs sales, thalidomide included, which in 1961 would earn 325,000 marks. A massive amount, especially when considering his salary was only 14,400 marks.

However, the company’s hand would be forced on the 26 November when the newspaper Welt am Sonntag (World on Sunday) reported Dr Lenz’s assertions that a popular sleeping pill was causing the epidemic of deformed births and what was worse the manufacturers had refused to withdraw the drug. The article called for authorities to intervene. Grunenthal withdrew the drug, stating it was due to the media frenzy rather than anything to do with thalidomide and Distillers followed suit in the UK.

Sources vary, but in all thalidomide caused at least 10,000 to 15,000 babies to be born in Europe and Canada with missing digits, arms and legs, and deformities of internal organs, causing many to die. Thalidomide likely caused thousands more deaths in utero; though, for obvious reasons it is impossible to estimate a number. It seems only under half of the victims survived to today, into their late 50s or early 60s. Many are still waiting for more than a token amount of compensation from the responsible pharmaceutical manufacturers.

I suppose its panic really going on. My dad was obviously panicking, my mum was sedated, the midwife I think was running around like a headless chicken, the GP was totally unused to anything like this.
I believe she was kept unconscious, she was given sleeping pills to just not wake up. I also believe that I didn’t see her for quite a while, about ten days or so. And I believe that my father was told that you know come down with anaesthetics and we can put her life at an end. Or it was even suggested to go and put me in the jungle where the animals could get to me and just forget about it.
But when I was born, they took me away and told my mother that I had no arms and no legs. And she said, 'I don't want to see the baby', because she said that she knew if she saw that she would love me because I was her baby. So there was that, that she knew there was going to be that bond if she saw me but she didn't want to love me if I had no arms and no legs because therefore I wouldn't have any life.
And my mum was sort of, I think her first reaction was, oh I’ve had one those babies. And then she said her next reaction was to sort of systematically look at my arms and my legs and work out what was missing and what I did have. And one of the things she said that I thought was really lovely was she looked at my fingers and thought, oh she’s got a finger to wear a ring on; if ever she gets married, you know, she’s got a finger. I don't think, I don't think until I had my daughter, I don’t think I realised how hard that was for her. And I think you know, nothing will ever take away the pain that she went through and probably still goes through. I mean I just think I wish that whole situation had been handled so differently for her. And I just can’t- I don’t think she has ever been truthful about how she really felt, I think she's just tried to put a brave face on it. But it must have been awful, really awful.
He said they're folded back and they're not developed as they should be. And my dad said to my mum, 'If you don’t want to keep her, we don’t have to keep her'. My mum said, 'well I want to see my baby', and the nurses then brought me in to her. And apparently my mum looked at me and she said, 'I’ll make you independent if it is the last thing I do'.

I originally wasn’t going to do an episode on thalidomide. After showing how pharmaceutical marketing was promoting drug use and confusing doctors in the last episode I was going to finally move on to talking about the people who used the drugs, and introduce ideas surrounding cannabis and heroin use. But I read a book Silent Shock about thalidomide and having read all this medical literature from the period, I realised that the practices which have since been identified as causing the tragedy were being complained about at the time. And as I have not seen anyone put the disaster in the context of these complaints, I thought I’d have a crack at it.

A good example to represent these complaints were these two articles published in a Medical Journal the Lancet in the summer of 61. They sparked an argument in the pages of the journal that lasted for months. In the last episode, we saw how in the mid to late 50s doctors were complaining about the ethics of drug marketing, by now these complaints had extended to drug testing. The first of these articles was by an anonymous author, a teacher at an American medical school.

The way drug testing worked in this time, was first the company would do toxicity tests on animals and humans to see if the drug was dangerous. Then the drug was sent out to people in the medical profession to conduct clinical trials to see if the drug worked. The anonymous author argued that there was also an ulterior motive for these clinical trials, and that was marketing. You know, send the unreleased product out to as many doctors as possible to get the word out about the drug before release.

And to get doctors to test the drug, companies deploy flattery:

...tell you at an early stage that you have been particularly selected in views of your qualifications, facilities, interest, brilliance... If you harbour a lingering doubt, you may be told that the well known university doctors at X, Y, and Z have just received the substance also and have very recently begun testing it-implying that you really should count yourself lucky to be mentioned in one breath with these important people.

This would tie into a point, he would make later, that doctors who really had no business doing clinical trials due to there lack of training or experience where being approached by drug companies.

He then complained about how drug houses had become quite careless in their toxicity tests and sometimes even included tests conducted on animals in the human testing section of the information clinical tester received. The author partly blamed many clinical testers try first and be sorry after attitude on how they were able to get away with this. Unsurprisingly this had led to several premature, faulty, injurious, and even fatal drug trials.

The anonymous author also highlighted how incentives offered by the drugs manufacturer may colour the tester’s opinion. Apparently the manufacturer could pay for a technician, offer personal grants, take the tester out to dinner or pay for them to attend a distant congress. Or in its more subtle forms have the firm's statisticians help interpret the doctor's results and even write their paper. Anonymous complained that this financial support could quickly lead to a situation where the tester and their lab was reliant on the firm for economic survival.

He claimed the results of this was journal articles on new drugs increasingly becoming positive and advocated for the drugs widespread use. Even if the results were not positive the conclusions could include statements like; "further trials of this interesting new substance are warranted", maintaining the idea that the drug may still hold some usefulness. He felt this disassociation between the evidence and the conclusion could leave the reader wondering if they were even written by the same person.

As stated, these articles caused a lot of debate and inspired a reply from J Gorringe, a Director at a British pharma company. He wrote that this money was not used to gain favourable results, we want good research on our drugs, otherwise, they will have to pull a drug after having spent a lot of money on producing and marketing it. And someone needed to pay for the cost of these trials. As for offering the use of the firm's statisticians, he claimed it was frequently accepted, and it never occurred to him that this could be open to misinterpreting results. Stating it was more to do with have the data analysed by properly qualified statisticians.

Overall Gorringe felt the original article painted an unfair picture of manufacturers motives. It should be pointed out that our anonymous author wasn’t necessarily saying this was the firm's motives - they certainly implied it - but was more commenting from the doctor's point of view if your clinical trial is totally financially dependant on a drug company, it may have some influence on you. The anonymous author points this out in a letter in reply to Gorringe’s reply:

Untoward pressures do arise during the conduct of clinical trials, as can be witnessed by those involved in them. This, in fact, is an inevitable component of our competitive society.
The point I was trying to make was that it behoves both physicians and industry to resist untoward pressures for the sake of the recipient of the results of therapeutic research-the patient.

In the original article, anonymous warned doctors not to be too trusting of pharmaceutical reps. Who if you remember, were like travelling salesmen sent around the country to promote the firm's drugs to doctors. Anonymous painted them as experts in the art of persuasion who would specifically target poorer doctors, plying them with free drugs for themselves and their family.

This claim also inspired a reply, from a pharma rep who objected to being painted in this villainous way by this and other articles, stating the GP is not some simpleton that can easily be swayed to prescribe useless drugs. Adding:

Providing we are always completely honest, the doctor is likely to try products for the recommended conditions. In this way, sales materialise and our employers are satisfied, but first and foremost, representatives of my acquaintance are always true to themselves.

Although he may be right that pharmaceutical representatives should not be seen conniving Machiavellian figures swindling poor doctors, the fact that doctors are likely to try the drugs they recommend does lend to the criticism, which was the theme the article we are about to talk about, that pharmaceutical companies were taking the role of educators.

In the same issue that this damning presentation of the situation in the US was printed, the Lancet ran an editorial which opened with the statement:

many doctors are beginning to be restive under what they regard as commercial pressures. The tendency, they feel, is towards transforming useful cooperation into a rather dangerous collaboration; and this feeling has enough foundation to make all parties think again about their role and their relationship.

It made some comment on the poor conditions of drug testing in the UK, pointing out that drugs were marketed without good enough evidence and that, “Though [pharmaceutical manufacturers] spend a great deal of money on clinical trials, much of this goes on what one may call nonne research-which expects the answer 'yes' and can usually evoke at least 'perhaps'.”

The editorial's main focus was on the profession’s inability to combat drug marketers. It seems the 'Mad Men' era of advertising was effecting drug marketing. As a result, the article complained, “Of late years an increasing proportion of the advertisements appearing in journals or distributed through the post have been clever rather than factual: they smack of the advertising expert rather than of the manufacturer himself, by whom most doctors would prefer to be addressed.” And this can certainly be seen in the adverts themselves. By 1961 drug adverts were full of what I would call wishy-washy language.

An example of this can be seen in a 1961 Bronchitis medication: “With its more powerful antibacterial action at lower dosages, Ledermycin sets a new therapeutic standard among broad spectrum antibiotics”. More powerful than what? Lower dosages than what? How does it set a new standard? Apart from fine print with the chemical name and dosage, which they may have to include, that is all the information the advert gives; one sentence. About four-fifths of the full page advert is a stylised painting of smoke billowing out the chimneys of an industrial town. This represents a trend of these adverts giving more space to eye-catching graphics rather than information.

Another is mainly taken up by a sketch of the great wall of China and the only information is dedicated to a building analogy."Master Builders, Successful[sic] and durable building requires suitable materials, properly used. Reconstruction of the body requires nitrogen, and Durabolin ensures the fullest use of available supplies. Hasten Convalescence with Durabolin." Again apart from the chemical name and dosage, that's all the information you get.

It should be noted that adverts were visual before. The Efocaine add for example back in 53, half of that add was a picture. But the information given was five sentences, as compared to the one-sentence offered by many adds by 1961. In fact, in comparing 1953 and 1961 BMJ issues, the rate of single sentence full-page adverts increased from roughly 3 per cent to 15. Over time these adverts were losing information about the drug in favour of sophisticated eye-catching and persuasive marketing techniques.

This can be seen in a letter written in reply to this article assumedly by a marketer - an asumption only evidenced by the letter exclusively discussing marketing. He felt all this talk that adverts should be strictly informative was ridiculous.

I am forced to the conclusion that much of the misunderstanding which exists between the industry and the profession arises from the fact that there is an apparent lack of knowledge within the profession of elementary business procedure, particularly as it pertains to advertising. For example, every advertisement contains an element of information and an element of persuasion, and there is no such thing as " straightforward information ". Taplin [the author of a book on advertising] puts it even more bluntly when he says " that anyone who suggests that advertising can in practice be a matter of information only is talking nonsense "...
While it would be foolish to suppose that all is well in the field of medical advertising, it should also be borne in mind that by demanding the right to prescribe freely for his patients the doctor creates the atmosphere in which medical promotion can flourish, and to suppress it forcibly is to jeopardise his freedom of prescribing.

Dangers to the medical profession's closely gaurded "clinical freedom" were often brought up when the profession made too much noise about government intervention.

To return to the Lancet editorial, it would go on to show how the corrupting influence of the industry in the US was also being felt in the UK. After discussing an American article by Charles May, which criticised doctors accepting gifts and the educational role pharmaceutical marketing took in the medical profession, the editor wrote:

Is it prudent, he asks, for the profession to become so largely dependent on the drug firms "for support of scientific journals and medical societies, for entertainment, and now also for a large part of their education"? Hardly any of us, perhaps, could read his trenchant and courageous article without risk of a blush somewhere.

The editorial certainly made it seem as though the practice of accepting gifts from firms was widespread in the British medical profession. After complaining how medical students’ training in developing a critical and detached mind was being sapped by various favours from manufacturers granted to themselves or their school, the writer conceded, “Yet, after all, which of us, his seniors, can say that we have never attended sponsored conferences or accepted entertainment?”

Going on to point out, “we should be rash to assume that even the most prosperous manufacturer supplies money habitually to medical groups or individuals without an object; and we should be very careful lest achievement of that object should lower the status of our profession or its members-young or old.” In other words, there is a reason behind these gifts and that is the hope that you will prescribe more of their drugs.

The editorial claimed that the medical journals themselves were particularly guilty of this as advertisements can be seen as a financial subsidy. This is not to say that advertisements were necessarily affecting the articles within the journal, doctors were free to criticise a drug and its use, but this reliance on marketing money gave Journals less flexibility in not advertising drugs that articles within the journal recomended against using. A problem was made worse by adverts generally being more entertaining and persuasive than the medical literature within the journal.

Again quoting Charles May the editorial stated:

The drab and prosaic legitimate journals must limp along on relatively meagre resources openly raised through paid subscriptions or stoop to sharing the promoter’s bounty by carrying his advertisements, which enshroud and often conflict with the editorial text. The beautiful and exciting magazines and newspapers from the industry can be given away, whatever the cost, because the expense is conveniently included in the price of products the physician is led to prescribe.

It is easy to understand why this would be, the journal articles are firstly written by doctors, pharmacologists and chemists, not professional writers or marketers who have dedicated their time to writing interesting and persuasive copy. Also the claims of the journal articles are limited by the scientific process. They do have to back up their claims. Marketers were certainly not held to their claims to the same extent.

As I said these articles inspired lots of letters to be written in reply, largely from the drug houses. To sum up the responses from the British pharmaceutical industry, many agreed with broad strokes of what was said in the two articles and that there was some need for voluntary reform on the side of the profession. However they would go on to state their company doesn’t conduct any of these poor practices and chastised the articles for generalising the industry due to the actions of a few bad-eggs. And there is truth in what they are saying, some of these companies were conducting careful and cutting edge research. Yet, their admittance that these bad-eggs exist does show that at least a minority were abusing the lax laws surrounding drug testing and marketing and the acceptance of this behaviour by many in the profession.

Another interesting replywas from Dr T Binns who felt out that neither of these articles pointed out that this situation was largely due to the apathy of the profession its self. Doctors are fully able to refuse to see representatives, ask to be removed from mailing lists and not prescribe their products. Also, he points out that clinical testing is still the profession's responsibility and many of the failings can be seen as the profession failing to install a proper system. His feeling that it was the profession’s fault that the industry so easily could take advantage of them is best summed up in his concluding statement: “It seems to me that in every country the profession gets the industry it deserves.”

This statement would form the title of the most comprehensive reply from a pharmaceutical industry worker. Published October 14 1961, two months after the original Lancet articles and a little over a month before Lenz blew the whistle on thalidomide, this article from a firm’s medical advisor painted a picture of the situation just as damning as the other two articles.

It pointed out most new drugs hold no great therapeutic advantage and tended to simply be copies of drugs that already existed, just with their molecule manipulated enough to get around patents. This meant aggressive sales techniques had to be employed to persuade doctors to prescribe one drug over its very similar competition. This had led to a situation where advertising claims became more and more aggressive.

if one conversationalist in a crowded room raises his voice, ultimately everybody else in the room will be shouting at the top of their voices in an effort to make themselves heard. Pharmaceutical houses have learnt from bitter experience that it is the policy of the loudest and most blatant advertiser which brings in the business, even from the medical profession.

As for standards of testing, the article argued there was a stark difference in standards. “The best we have are the best in the world and recognised as such by colleagues everywhere. The worst are little short of malpractice.”

The correspondent also showed how the profession could be corrupted. Apparently many senior doctors in Britain received large fees from individual drug houses, yet rarely disclose this information when writing articles describing the merits and promoting the use of new drugs. The article also complained about the widespread use of paying General Practitioners substantial amounts to undertake therapeutic trials. Unlike hospital trials, in the face of financial incentives, GPs did not seem to request much supporting medical evidence and apparently would produce favourable results at a ratio of ten to one. The article’s slant on who was to blame for this is made clear within the statement: “Before it can attack the ethics of the industry, the profession ought to put its own house in better order.”

It should be noted that a GP research group wrote in a reply which convincingly challenged these claims, at least in the practices of their organisation. So this aspect is likely exaggerated. However, one aspect of GP trials that this correspondent does not mention, which may also account for the popularity, is anonymous’ ulterior motive for clinical trial, they work as marketing. As GP’s will be the ones prescribing many of these new drugs it stands to reason to introduce them to it early. Like a pre-release sneak peek.

The article did call for some light government intervention, however, the main focus was for the profession and medical journals to do more about lax clinical trials and to stop falling for marketing techniques so easily. The correspondent's frustration over the declining situation can be seen in his conclusion.

I believe that the most important and most urgent steps to improve the present relationship between the industry, the profession, and the patient could – indeed should – be taken by the medical profession itself. In the long run, all would benefit, including the industry. I see this problem as one who enjoys the work of developing and testing new drugs, but who is also subject to repeated pressure to lower the standard. For the lowering of standards there are very cogent business reasons first, the success of competitors who have lowered theirs, and secondly, the gullibility of the medical profession.

This calls into the question the claims made by the industry and parroted by politicians and the press in the last episode, that aggressive marketing and government inaction was needed for the industry to produce good drug research. What was presented here was the opposite, hyper-competitiveness and lack of government oversight was leading to worse research. And with the gift of hindsight, it is easy to see why this would be. If a situation exists where you do not need to back up your marketing claims, why invest money in expensive drug trials. What was being rewarded was not high standards of research but aggressive and sophisticated marketing.

On top of this, these articles show that by 1961, at least, the existence of poor drug testing, an epidemic of misleading marketing claims and a worryingly close relationship between the industry and the profession was an open secret.

To return to thalidomide, many of these complaints would play out in its story. Distillers was a wiskey company that had branched out into pharmaceuticals. However not wanting to go through the expensive business of researching their own drug, they instead bought the right to sell the promising sedative thalidomide in the UK from Grunenthal in 1957. Distillers would sell the drug under the name Distaval. As mentioned in the introduction if they marketed it successfully enough the company stood to make a lot of money.

Despite this chance of riches ahead, Distillers performed their pharmacological testing on the cheap. The company’s pharmacologist George Somers later admitted:

I did not have the time to carry out my own long-term research on [thalidomide] before it was launched here. It was early days in the establishment of [Distillers] as a drugs company, I had little assistance, and I was working on three other drugs at the time in very cramped conditions.

Somers also said, that if he had had more time to test the drug, he would have thrown it out the window.

Instead of conducting their own toxicity tests, Distillers relied on Grunenthal’s, which was severely lacking. As for clinical testing, Distillers provides a perfect example of the anonymous author’s ulterior motive behind clinical trials. They simply sent samples out to a large number of friendly doctors. Distillers medical advisor Dr Walter Kennedy wrote in a letter to Grunenthal that this scattergun tactic might not satisfy ‘medical purists’, but these tests were easy to arrange and aroused interest in the drug. This wasn’t a clinical trial, it was a marketing campaign.

As for the actual adverts printed in the BMJ, it is not surprising that Distillers would latch on to their claims of safety, even with their lax testing. Claiming your drug was safe was an obvious and endemic tactic during the 50s.

In a 57 article tranquilliser Miltown would be advertised as:

Uniform in action, and remarkably free from side reactions, Miltown acts safely and selectively to calm restlessness and irritability of anxiety states.

The amphetamine advert on the next page proclaimed:

Fat people die first – as any insurance company knows. To live longer, they must eat less.
Dexedrine ' is the safe, effective drug for the control of appetite in weight reduction.

The benefits of advertising the safety of your drug to doctors are self-explanatory. With worries over the dangers nicotine and tar tobacco companies had even got involved. A 1955 Pall Mall add in the BMJ bragged of “32% less nicotine … more Virginia flavour. Pall Mall traps 32% of the nicotine and 3,300 microgrammes of tars per cigarette. Watch the Filter change colour as you smoke. Britain’s first built-in filter, Pall Mall, Pleasure plus protection.”

As we explored last episode, despite doctors complaining that these adds were not being held accountable for their claims, nothing was done about it. So as the correspondent from the industry pointed out, the advertisements became louder and bolder in their claims. While Distaval originally ran with the wishy-washy slogan ‘Safe sedation and sounder sleep’, by 1960 this drug which had barely any adequate testing was probably yelling the loudest, advertising as “The safest sedative known”.

It would be a GP called Leslie Florence that first challenged this claim. Florence learned about thalidomide in upon its release 1958. Unsurprisingly, he did not learn about it from some balanced report in an academic journal, but from a distillers rep armed with free samples and the super-safe, super-effective sales pitch. Another example of the pharmaceutical companies educating doctors on what drugs to use. Florence and his three-year-old both suffered from eczema which made it hard to sleep, so he excitedly used it on himself and his son. He was very impressed with the results and started liberally prescribing the apparently side effect free drug. However, by the end of 1959, he and three other patients started developing symptoms of peripheral neuritis, which is essentially nerve damage.

First it was tingling in my feet and then in my hands, an occasional lack of steadiness on my feet, and cramping at night.
I thought it curious that all four of us should develop the same symptoms at about the same time. I studied the records and realised that we had all been taking Distaval for an extended period.

After a back and forth with Distillers, they reiterated that thalidomide was non-toxic and that he look in other places. However, the fact the symptoms subsided after he stopped using the drug aroused his suspicions and in December 1960 Florence had a letter published in the BMJ titled, Is Thalidomide to Blame? The letter essentially presents the evidence he had, symptoms of nerve damage started in people who had taken the drug and subsided when they stopped. He then asked if anyone else was finding similar results.

Beyond the starting the conversation in Britain that thalidomide was not all it was made out to be, its importance was much greater across the Atlantic, in the US. At this time FDA doctor Frances Kelsey was investigating whether thalidomide should be cleared for sale in the US. After she read Florence’s reports of nerve damage in the BMJ she delayed the drug’s release until she received better tests on the drug's toxicity and interestingly its effects on the foetus (more on that later). Florence’s letter and Kelsey’s refusal to release the drug without adequate tests undoubtedly saved the US from the worst of the thalidomide disaster.

In the UK replies in the BMJ started coming in confirming Florence’s suspicions. The first one interestingly enough was from Distillers themselves. They admitted nerve damage seemed to be a side effect of the drug, although a rare one. Despite this Distillers still ran the “This child’s life may depend on the safety of Distaval” advertisement described in the introduction for months to come. And if we look at a timeline of reports in 1961 it is easy to see how these advertisements in the BMJ telling people to "depend on the safety of Distaval" were drowning out doctors reports discouraging the drug's use.

On the 7 January, the same issue Distillers confirmed Distaval caused Nerve Damage, the front matter told doctors to "depend on the safety of Distaval."

21 January again "depend on the safety of Distaval."

28 January a letter from members of a neurological unit claimed to have 5 patients suffering from nerve damage due to Distival.

18 February "depend on the safety of Distaval."

11 March "depend on the safety of Distaval."

18 March "depend on the safety of Distaval" in the front pages and a letter from a doctor saying Distival was suspected of causing nerve damage in two patients in the back.

24 June "depend on the safety of Distaval." This was the last time this add would run in the BMJ.

Ignoring the unethical practice of Distillers in continuing to run an add proclaiming Distaval to be safe despite knowing this to be untrue. But if we examine the behaviour of the BMJ in this period we can see how their reliance on advertising money meant that they were unable, or unwilling to pull an add which letters published in their own journal from not only doctors but the also manufacturer its self admitted was untrue. In a newspaper article afterthalidomide’s role in causing birth defects fully appreciated and felt, a doctor was asked why these early warnings of thalidomide’s effects had not discouraged doctors from prescribing the drug. He answered that presumably not every doctor reads the BMJ. This may well be true but this timeline shows that if a doctor was only an occasional reader of the Journal he or shewas much more likely to see adds proclaiming the drugs benefits than letters warning against its use.

On the 30 September, around the time Lenz was investigating the rate of malformed births in Hamburg, the BMJ published a definitive article linking thalidomide to nerve damage. It was a study of 13 patients who had developed neuropathy after taking Distaval. The author’s conclusion of their investigation were reported thusly:

Our patients developed symptoms from 2 to 18 months after starting regular medication, which is suggestive of an aetiological relation, and this is supported by many of the unusual clinical features that were common to the group. A careful study of our cases has shown that only one patient had taken any substance other than thalidomide to which neuronal damage could be attributed. In this case the intake of alcohol had been for a relatively short time and the signs were very different from those commonly found in alcoholic peripheral neuritis. It seemed reasonable, therefore, to attribute the neuropathy here described to thalidomide.

How was it that quote the Lancet editorial described the language of journals as compared to marketers? Drab and prosaic.

“It seemed reasonable, therefore, to attribute the neuropathy here described to thalidomide.”

“This child’s life may depend on the safety of Distaval/ depend on the safety of Distaval.”

The article seems to have been ineffective at discouraging the drugs use. A month later, Heathfield, a doctor at a neurological clinic wrote in to complain that Distaval was still being widely prescribed, and would soon be the most common cause of neuropathy at the clinic. He also pointed out the irony that although the manufacturer admitting to this side effect, Distaval was still being advertised as the ideal hypnotic. One reason he felt the profession had failed to combat this marketing was the nomenclature problem we talked about last episode. In the letters and articles it was referred to as thalidomide but the drug was more commonly known by its trade name Distaval. As if to prove Heathfield’s points, in this very issue the BMJ ran another add for thalidomide, this time it was mixed with aspirin and phenacetin and was advertised under the name Valgis. Its slogan was “a SAFE hypnotic/ analgesic combination”.

Distillers obviously felt that marketing claims did not have to represent the reality of their product. Loose marketing ethics are also being displayed by the British Medical Journal. During this period the pages of the medical journal were full of articles stating that tobacco caused cancer and that smoking should be discouraged. Yet, the BMJ continued to advertise tobacco. And it is important to note that this is the publishing arm of the British Medical Association, which boasts the membership of tens of thousands of doctors. This is not some rinky-dink operation. If any publication had the financial security to exercise some influence over the products that it advertised, it would be this one. Although at the moment we are not talking about the drug in the context of phocomelia, nerve damage is not a non-issue. For many, it would take years for the symptoms to totally go away.

It should also be remembered that we are only talking about a sleeping pill here. There were many other options out there. A bit before this, some Grunenthal executives drove over to East Berlin and tried to sell thalidomide to the communists. They were promptly shown the door. The East Germans had seen reports that it caused nerve damage and told the execs they did not feel the drug was needed.

Due to the number of people involved in the medical profession, it was always going to be slow to react and adapt the same opinion as those East Germans. But the British Medical Journal and other publications willingness to continue to publish Distillers false claims only served to confuse the matter and make this process slower. Unfortunately, the stakes in this case were higher than just nerve damage. They were the rate of babies being born with massive birth defects. Ultimately it was Lenz leaking that story to the press in late November that would not only put an end to Distillers marketing, but also the drug itself.

With the realisation that thalidomide caused birth defects, Distillers pharmacologist George Somers did some tests on pregnant animals and quickly found that thalidomide caused the birth of defects in rabbits. This left Grunenthal and Distillers with somewhat of a problem as they now needed to develop an excuse to explain why they did not test thalidomides effects on pregnant animals before. They settled on proclaiming that pharmacologists the world over did not conduct tests on pregnant animals as no one knew drugs could cross the placenta barrier. In other words they were just following the industry standard. It is an argument Grunenthal still cling to to this day.

Now the fact that Frances Kelsey, in early 61, wouldn’t release thalidomide in the US without pregnancy tests, should be your first warning that this statement is not true. In reality there were many reports throughout the 1940s and 50s which showed drugs could have an effect on the foetus. Other companies had realised the potential dangers drugs could have on the foetus and tested on pregnant animals. During the 50s Parke, Davis and Co. for example, which J Gorringe, who wrote that letter in reply to the Lancet articles, was a director of, conducted studies on how their drugs effected the foetus. In fact, ICI and Smith Kline and French, two other companies that wrote in to complain about those Lancet articles, did tests on pregnant animals too. Now this is not to say that this was the norm, but the industry standard that Distillers and Grunenthal excused themselves with were not the ones that read those Lancet articles and felt the need to write in and request not to generalised with the bad eggs. Or whose testing practices that correspondent from the industry described as “the best in the world and recognised as such by colleagues everywhere”. Distiller’s practices were more in line with what that correspondent stops just short of accusing of malpractice. On top of this there is a great deal more evidence of Distillers and particularly Grunenthal ignoring warning signs and suppressing criticism of thalidomide, which I do not have the time to go into.

Unsurprisingly parents of the victims did not think much Grünenthal and Distillers excuse. As one mother wrote to the Guardian:

The makers of thalidomide must be very naive to say they never tested the drug on pregnant animals because no one else was doing it. They must surely realise that of all people who take drugs, pregnant women are the most vulnerable.
Is the firm going to do nothing in the way of recompense for these maimed children? Withdrawing the drug now will not help them.
No one can imagine the misery and heartbreak parents suffer when a deformed child is born to them. Because of thalidomide my baby son has no arms.

Its important to appreciate the psychological damage that this drug inflicted. Many parents would go through theer life with extreme guilt over what they had done to their babies by taking this drug.

And she said, 'oh you know you’re one of the thalidomide babies.' And I said, 'well why didn’t you tell me before?' And she said, 'because I thought you'd hate me.' And I think, for her it was an immense relief to hear, ‘Of course I don't, you know, that's ridiculous why would I hate you?’ I think a lot of women have, are and will go to there graves with an enormous block of guilt weighing them down. Because no matter what you say about, you know, look it was a load of scientist, it was a greedy corporate organisation, it was government negligence, they were the ones that did the swallowing. So yeah, we’ve had that conversation, and yes Iv’e tried to be reassuring, and has it helped no. And I don't think it has and I don’t think it does in most cases.
She didn't say an awful lot about it other than her guilt, because she said, 'you can take a horse to water but you cant make em drink.' That was her attitude to the whole thing. She totally blames herself, because the doctors prescribed the drug but it was her decision to take it. I couldn't get her to think any other way. I did try, because I never ever blamed her.
It was difficult but yes we have always spoken about it. I knew from a very early age -I think 5 or 6 - that my arms were different to everybody else's because mum had taken a drug. So I actually do remember the day that my mum and I spoke about it and we sat on the stairs in my mum’s house. And Im not quite sure what provoked the conversation but I do remember her telling me why she took the drug and she didnt know that that's what it would do and that she was really very very sorry. And I do know that she carries the weight of the guilt today still. And probably, apart from everything, that effects me the most is her guilt. Because I do not hold her responsible whatsoever she is as much a victim as I am. And she went through hell as well. As difficult as my life has been, she has gone through it every step of the way with me. And I  do wish she would absolve herself of the guilt, I really really do. That would be my wish.”

Although the efects of the drug were first leaked by the German press, in Britain the press showed a surprising level of gullibility. Early in 1962 some sections of the press would report on thalidomide in the context of the poor practices of the industry. The Guardian would put out a couple articles like this, and the Birmingham Post released a very inflammatory article which asserted the pharmaceutical industry was essentially using the British public as its poison tasters.

However, the press would not truly become interested in the story until the summer of 62 and by this time they had been briefed by Distillers. The Guardian's medical correspondent Alfred Bryne swallowed Distillers propaganda wholesale. In an article in late July Bryne explained away Distillers and Grunenthal not testing thalidomides’ potential effects on the foetus as “pharmacologists the world over did not consider it necessary to try to find out if any new drugs might have such an effect”. This was in no way unique to the Guardian, pretty much across the board the press accepted Distiller’s story.

A Financial Times article released a couple days before seemed unwilling to even criticise the drug stating:

Thalidomide is an excellent sedative drug which had been widely adopted by doctors… on the grounds that it was safer, more effective, and less likely to produce a hangover than the barbiturates

There are no mentions that the drug caused nerve damage. It would go on to say the drug had undergone careful laboratory and clinical trials.  The Financial Times then claims that Grunenthal withdrew the drug as soon as it received information of it causing phocomelia, which we know from our introduction was not true. The Financial Times then announced to the people of Britain “If the British pharmaceutical industry maintains its present high standards the public has little to fear”.

Distillers was successfully controlling the narrative in the UK. And they would not need to for much longer. In November the parents would start a lawsuit which placed a gag order on the press. And to quickly highlight this lawsuit essentially it was a mess. The court system totally failed the parents and it took them a decade to even get a meager payout. In disgust the Sunday Times’ investigative arm, which throughout this period had acquired a lot of evidence, broke the gag order and released an article on Distillers and Grunenthal’s malpractice. This caused a swing in public opinion and Distillers, who was mainly a drinks company, started facing boycotts. Under this public pressure Distillers upped their total payout from just over 3 million pounds to 20 million pounds.

To quickly examine the Government’s reaction. Initial was muted to say the least. When thalidomide first came up in a parliamentary debate, the Ministry of Health (headed by the now infamous Enoch Powell), pretty much took the line that as politicians this is none of our business. The debate took place in the context of Lord Cohen, who was a government researcher double checking drug trials, recently stating that only under half of the drugs released in the last year had had adequate clinical trials.

Labour MP Pavitt asks the Ministry of Health just how many drugs with poor clinical trials has the NHS been prescribing, and what steps are the government taking to protect patients?

Edith Pitt, who was one of Enoch Powell’s underlings answered, “It is not for my right hon. Friend to judge when adequate clinical trials of drugs have taken place. It is the doctor's responsibility to decide whether he is justified in prescribing a particular drug.”

Pavitt then asked in the context of Cohen’s statements and thalidomide causing birth defects “Is it not the Minister's duty to protect the patients in this respect?”

Pitt simply answered that responsibility lay with the industry and the profession.

In general Enoch Powell and the ministry of health did not cover themselves in glory in the aftermath of the catastrophe. They refused to ever criticise the pharmaceutical industry, continually stating it was of the highest standard and parroted Distillers’ claim that there was no way this could have been avoided. The Ministry also refused to back an inquest which would have investigated how this happened. Enoch Powell himself would meet a delegation of parents and come off cold and uncaring. Apparently the tone of the meeting was, you better not try and sue the government. Which perhaps they could have as through the NHS it was government employees who recommended  thalidomide to these women .

However there were political calls for reform. Baroness Sumerskill, who as we saw last episode had been criticising the practises of the industry for a while, would not shut up about it - from Enoch Powell’s point of view. She continually called for the government to do something to protect the public and even unsuccessfully campaigned for an exception to be made in abortion legislation to make it legal for pregnant women who had taken thalidomide to get abortions. But calls for the government to look into drug testing certainly were not limited to the Labour party, Conservative back-benchers also started asking uncomfortable questions about government responsibility, usually with the caveat that the industry had done nothing wrong.

Bowing to this pressure in 1963 the government funded the Safety of Drugs Committee. It would evaluate the results of toxicity and clinical trials to see if a drug was safe enough to be brought to market. It also monitored undesirable effects of a drug after marketing. Due to the political beliefs of the Conservative party however this was simply a voluntary situation not legislation or law. When the committee started to function in 1964 the pharmaceutical associations simply swore to committee that they would follow their instructions.

It took five more years and a change in government for actually legally binding legislation controlling pharmaceutical firms to be put into place, in the form of the Medicines act 1968. this essentially gave the safety of drugs Committee legal power and finally did something about the marketing claims. The Act stated standardised clear factual information had to accompany marketing material, giving the Committee the power to hold the industry accountable to their marketing claims. This marked the end of the Wild West days of drug marketing in the UK.

And the thalidomide disaster inspired reform across the world. Even the US, which was thankfully spared from the worst effects, would strengthen the FDA. Prior to this the FDA was quite a corrupt organisation and thalidomide not being cleared for release had more to do with Frances Kelsey’s ethics and diligence, than the effectiveness of the FDA. The whole incident itself is an important case study to be aware of, as even if you do hold liberal views toward how the pharmaceutical industry should be controlled and have salient arguments about how government intervention has been a travesty. It is hard to argue that some kind of vigilance over the relationship between the profession and the industry is not  needed, lest their useful cooperation devolve into collusion. It is a lesson which is still relevant today, as any keen observers of the opioid epidemic know.

And if you are glad to see government oversight, these victims are probably who you have to thank for it. By and large, neither the profession nor the industry wanted any government control and with a few notable exceptions, politicians weren’t interested in implementing oversight either. Here are your martyrs for the control over drug testing we enjoy today. However for the victims this fight still is not over as they seek for Grunenthal to accept responsibility for what they did.

Grunenthal is still a privately owned company. The Wirtz family owns it today just as they did in 1960. It does not have share holder demanding returns. The Wirtz family’s personal fortune has been variously estimated at between two and three billion euros. It would not drive that family into penury or bankruptcy or poverty to loosen the purse strings and behave in a more generous fashion towards survivors.
Why are we having to do this? Why are we having to struggle and fight and campaign and and even even have to ask for compensation that we deserve? Why aren't they with their thousands- millions and millions that they are earning, why cant it come from them that we are sorry and this is you know you really deserve this, you really do deserve it? I know there are a lot of us but then that’s your products thats caused all this. So my question to everybody - the whole world - is why is everybody standing by and letting us campaign and letting us fight for what is should be rightly ours? You know, the whole world is watching us. But, you know, publicity yes - the newspapers are doing it because they need a story, television is doing it because they need a story - but what about us, we are not stories we are human beings.
I not only want the money, I want the revenge. I want the revenge, you know, they killed five thousand children, they made another five thousand children’s life miserable, they made the life of ten thousand parents awful. They are responsible, and they should pay for it.