Remembering Thalidomide

What do these names have in common: Distaval, Contergan, Kevadon, Tensival, Softenil, Asmaval, Valgraine? Something meretriciously soothing about them suggests the medical ad-man, and in fact they’re some of the 35 or so trade names once used round the world for the drug thalidomide. Looking at that drug’s tragic history from the sales end like this (and it did start out as a freely purchasable medicine) is a helpful reminder that the delinquency behind it was much more commercial than scientific. Thalidomide was aggressively and mendaciously marketed at every stage, in defiance of the gathering evidence against its safety. Really its trade name should have been Moneymaker (like the commercial tomato variety, but with a good deal more justice). One small but characteristic instance of this: when Distillers Company (Biochemicals) Limited, which had bought the British rights to thalidomide from Chemie Grünenthal, was told by its own pharmacologist, George Somers, that a new liquid formulation of the drug had proved thalidomide babydangerously toxic, the Managing Director muffled the information in a notable euphemism – “I understand that it has not yet been possible to develop a formulation which compares favourably in terms of toxicity with our tablets” – and the liquid version was put on sale just the same (in July 1961).

That the testing on animals had been unhelpful is true enough, but only in so far as such tests are inherently unhelpful. True, the Chemie Grünenthal laboratory had tested the drug only for efficacy and toxicity in mature animals, and not for effects on their offspring. But almost certainly that omission made no difference. Notoriously, it proved difficult both during and after the scandal to confirm thalidomide’s teratogenic effect in animals. Thus the physician who first suspected and made known the harm being done by the drug, William McBride, tested it for that specific harm on mice and guinea pigs, and got no results. It made him doubt for a time the soundness of his own suspicions. The actor Mat Fraser, survivor and brilliant scourge of thalidomide, is surely right in saying that animal tests actually delayed the withdrawal of the drug. The human evidence, by contrast, was prompt and conclusive, but it was not acted upon.

Anyway, the animal kingdom was indeed scoured for results, often with enormous doses of the drug (“we just stuffed it into them”, McBride said), before the ‘right’ species were eventually found: New Zealand rabbits and certain non-human primates. By 1966, a hundred or more papers had been published on such hit and miss animal tests. A review of this unsavoury literature concluded that, since the different species varied so much in their responses to the same drug, “it is rather difficult now, as ever, to apply in humans the experimental findings.” The writer in this case was a scientist on the staff of Chemie Grünenthal, so he was not exactly impartial; still, his article appeared in the very respectable peer-reviewed journal Arzneimittelforschung, and its conclusion seems very well justified. The Sunday Times book about thalidomide, Suffer the Children (1979), quotes it with ironic reservation, but admits readily enough the complementary fact about animal tests, that negative results provide no reliable guidance either:

the biochemical variations between human and animal species are so great that even if a drug shows no ill effect in animals, it may still do so once human use begins… When we describe a drug as “safe”, therefore, what we should really say is that it is a drug that has not yet been found unsafe.

The animals, in short, can tell us nothing that we really need to know.

These unhappy recollections of thalidomide are prompted by yet more medical ‘disasters’ in the news. In January, one participant died during tests in France for the company Bial of a painkiller/tranquilliser; a few weeks later, the drug Pacritinib, developed for the treatment of blood cancer, similarly proved to have, as the FDA put it, “a detrimental effect on survival” (I collect these weird euphemisms). This last misfortune was felt to be especially shocking because it happened in a ‘phase 3’ trial: i.e. after two earlier stages of clinical tests in humans. Evidently it is agreed that human tests at least can be expected to provide reliable guidance – and correspondingly that nobody should be much surprised at being misled by the results from animals. This is no doubt right, although unfortunately, as Suffer the Children says, and as records of adverse reactions in patients continually show, no drug can ever be called absolutely safe.

Bial’s representatives have insisted, truthfully I’m sure, that they followed all the right procedures. They have even cited the Declaration of Helsinki, that honourable legacy of the Nuremberg Medical Trials which laboriously, revision after revision, protects the interests of research ‘subjects’ from abuse, provided they’re human. And it’s worth saying a bit more about that remarkable document. Here are some of its principles: that subjects should not be asked to take risks for research they don’t stand to benefit from, that the interests of research should “never take precedence over the rights and interests of individual research subjects”, that the subject’s consent or dissent should be respected even where it cannot be classified as “informed”, that “vulnerable” (= easily exploited) groups need particular protection. Note how all these principles exactly fit the situation of non-human animals. In fact the Declaration is a great monument to speciesism, haunted by the animals that it doesn’t (dare?) mention, except the perfunctory once: “The welfare of animals used for research must be respected.” Since the drug which Bial had been testing on its animals was a pain-killer, with all that implies as to the nature of the tests, even that one crumb of compassion from Helsinki’s table probably didn’t do them any appreciable good.

There’s an ugly sense in the Sunday Times book (and more generally) that the painful glare of human suffering properly puts the suffering of other animals into complete darkness, and even that willingness to plough through laboratory animals is to be taken as an index of proper medical humanitarianism – though that’s never made explicit, of course. (It fits George Bernard Shaw’s shrewd suggestion that vivisection shows the ancient superstition of propitiatory sacrifice living on into modern times.) Thus, speaking about another of Grünenthal’s products, an antibiotic called Supracillin, the Sunday Times says,

Somers of DCBL spent a great deal of time trying to verify Grunenthal’s claim that Supracillin would not destroy the hearing of cats. To Mueckter’s displeasure [Muekter was head of Grunenthal’s research laboratory], he managed at last to show that the claim was entirely baseless. [italics in the original]

All the emphases here are designed to contrast the scientific diligence of Somers with Muekter’s hustle (“great deal of time”, “managed at last” “entirely baseless”); what all this thoroughness meant for the cats is unmentioned, probably unthought of. That word “entirely” is especially chilling.

A more recent account of the thalidomide affair (Stephens and Brynner, Dark Remedy, Cambridge, Mass., 2009) is able to take a longer view, and does indeed attempt a general “moral”, as follows: “Wherever there is an absence of compassion, individual or collective, a lesser human attribute will fill the vacuum.” There’s a slightly bogus suggestion here that a real law (in psychopathology? cybernetics?) has been uncovered, matching the one in physics, but there’s also some useful if obvious truth. Better to say, probably, that the more immediate and urgent motives – notably the commercial motive and careerism – will always tend to drive out more removed ones like compassion and even ordinary caution. (And that seems to be the lesson the U.K. government was taking when it passed the 1968 Medicines Act, with its new array of regulations.) But like their predecessors (and like the Medicines Act itself) these authors don’t include animals in the scope of their “compassion”. Unhappily illustrating their own ‘law’, they allow horror, fear, indignation, to drive out disinterested pity.

If it had been impossible for some reason (decency, perhaps) to use animals in medical research, we would certainly by now have made far greater progress in human models of one sort or another than we actually have, and accordingly in medical safety. William McBride himself subsequently wrote, “we will have more thalidomide-type tragedies in the future, perhaps not on such a large scale, but as man is different from other animal species it is likely that, no matter how thoroughly new drugs are tested on animals, species differences or synergistic actions [i.e. unpredicted whole-body responses] will occasionally betray us.” Thalidomide remains uniquely dreadful among medical disasters, but we have not changed the situation or the attitudes which made it possible.

 

Notes and references:

The picture at the top, Thalidomide Baby (oil on acetate), is used by kind permission of the artist, Josephine Storer of Oxford Brookes University’s School of Art and Design: this strong and most poignant image has saved me having to attempt in words the sorrow and sympathy which ought to preface any discussion of this subject.

Suffer the Children: the Story of Thalidomide, was written by Phillip Knightley, Harold Evans, Elaine Potter, and Marjorie Wallace, and published by Andre Deutsch. Quotations are from pp. 22, 23, 61, 88, 274. The Sunday Times newspaper, I should recall here, played a crucial and even heroic part in exposing the scandal and getting justice for the people affected by the drug. The quotation from Dark Remedy: the Impact of Thalidomide and its Revival as a Vital Medicine is from p.201. Both these books are well worth reading, and the second (as its title shows) talks about thalidomide’s controversial reappearance as a treatment for leprosy and some cancers.

The final quotation is from a letter which McBride wrote to the Daily Telegraph in 1973, as re-printed in Richard Ryder’s Victims of Science, NAVS, 1983, pp.174-5.

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