Thalidomide

Much of the following information is taken from the evidence exposed during the Thalidomide trials and from http://www.health.org.nz.

    (I) Thalidomide was a drug, which after years of extensive animal tests, was first marketed as an over-the-counter sedative: it came to be used by pregnant women in many countries during the late 1950s and early 1960s as a treatment for morning sickness.

    (ii)In fact, before being marketed, the danger signs had already appeared: during the 1950s at the University Clinic at Bonn, Thalidomide had been tested on 140 children, seven of whom were less than a year old. Forty children, most of whom had brain damage, had been given the drug for up to nine weeks. The parents were not asked for their permission, nor were they informed that their children were being treated with an entirely new sedative. Doses used were 11 to 20 times higher than the recommended dose for adults. Half the children were mentally disturbed or had brain damage.
    Other children also received Thalidomide in the same high dosage. One child had a circulatory collapse, one died from a congenital heart defect, a three-month-old baby died from heart failure, a twentyone-month-old baby temporarily lost her vision. The doctor responsible stopped using the drug when he heard that his medical colleagues had similar experiences with Thalidomide (Although twelve years would elapse before Thalidomide was withdrawn from the market).
    In 1955, one year before the commencement of the marketing of Thalidomide in its various formulae, three physicians, along with a Professor Kloos, took part in a symposium arranged by Chemie Grünenthal at which they reported to the company unsatisfactory experiences with Thalidomide. However, these were ignored.

    (iii)In 1956 the pharmaceutical companies (then) SmithKline and French (now SmithKline Beecham) revealed that even when used in very high doses Thalidomide could not induce sleep in mice. When administered at doses 50 times larger than that claimed by Chemie Grünenthal to be 'sleep inducing' this company could still not achieve the hypnotic effect in animals that it had on humans. Nor when given 650 times the dose effective in humans. This was substantiated and confirmed at the thalidomide trial by pharmaceutical companies Richardson-Merrel and Ciba.

    (iv)In November 1956 and October 1957 Thalidomide was marketed in Germany by Chemie Grünenthal. Sales rocketed as many pharmaceutical companies produced the drug under license to Chemie Grünenthal from as early as 1955 and 1957. In 1957, after launching Contergan (Thalidomide) in West Germany, reports began to appear regarding peripheral neuritis which revealed thalidomide's toxic effects on the nervous system of the user.[1]
    Such a suspicion was suggestive enough to cause Dr Frances Kelsey, the Medical Officer of the American Food and Drug Administration, to reject the pharmaceutical company's application to market Kevadon (Thalidomide) in the United States, because among other reasons, she was not satisfied that the drug would be safe to take during pregnancy. Her handwritten note on the original memorandum reads: 'This was based on peripheral neuritis symptoms in adults'.
    Despite the reports, thousands of cases of peripheral neuritis and a growing number of cases of deformities being advised, the firms responsible for the manufacture and distribution of thalidomide resisted moves to withdraw the product. As resumed animal tests did not duplicate the deformities, they saw no reason to remove the drug. In 1958 Chemie Grünenthal advised 40,000 doctors: 'In pregnancy and during the lactation period the female organism is under great strain. Sleeplessness, unrest and tension are constant complaints. The administration of a sedative and a hypnotic that will hurt neither mother nor child is often necessary'. (This was to encourage gynaecologists and obstetricians to prescribe Contergan and Contergan Forte (Thalidomide) to patients).
    The pharmaceutical company (then) SmithKline and French reported ill-effects from the drug and the same problems were confirmed by doctors observing their patients through to 1959. Chemie Grünenthal minimised the reports by ascribing them to overdosage and prolonged usage. Then followed a surge of universal medical agreement that severe nervous damage was being caused by Thalidomide.

    (v)On 27 August 1959 one of the Chemie Grünenthal partners in Basel gave the following report on the situation in Switzerland: 'Twenty well-known physicians have now informed our public relations men that they themselves, or their patients, have still had severe side-effects the morning after taking one whole tablet of Softenon Forte (Thalidomide) in the form of extreme tiredness, tremor (shaking) of the hands etc'. Professor Ludwig, head doctor of the second medical section of Burgerspital, Basel, added: 'Once and never again. This is a horrible drug.'

    (vi)In September 1959 the use of Contergan (Thalidomide) was stopped in a German Hospital because of severe reactions. On 3 November 1959, a written report was received by Chemie Grünenthal from the neurologist Dr Ralf Voss of Dusseldorf reporting more adverse effects. Dr Voss asked if Thalidomide could cause damage to the peripheral nervous system. Chemie Grünenthal replied that such effects had never been observed before. At the trial this statement was proved false.

    (vii)In December 1959 Dr Somers, a scientist in Distillers laboratory (Chemie Grünenthal's licensee in England), reported grave doubts about the safety of Thalidomide which was being widely advertised as a very safe drug. In an internal report Dr Somers wrote: 'Hitherto thalidomide has shown no demonstrable toxicity and mice have survived oral doses as high as 5g/kg...The observations that our formulated suspension is toxic is disturbing for it means that if we market in this form our claims are no longer justified and it is suggested that the formulation is amended to avoid this situation'. On 2 January 1960 Dr Somers again expressed alarm: 'The fact that it [Thalidomide] can be toxic is the worry. You will appreciate that our claim for non-toxicity would not be valid with this preparation'.
    In reply Chemie Grünenthal informed Distillers that they had repeated Dr Somers' experiments and had arrived at the conclusion that the preparation was completely non-toxic to the mice used at Chemie Grünenthal, and that the British mice they had used must belong to some particularly sensitive strain.

    (viii)By 1960 sales of Thalidomide were stepped up, despite reports of malformations caused by the drug which now came from all over the world. At this time it was being marketed by 14 firms in many countries under 37 different trade names and sold without perscription. It was combined with other drugs like aspirin and prescribed widely for headaches, migraine, coughs, colds, flu, asthma, neuralgia, nervous debility, to quieten lively babies and to help pregnant women to sleep.
    Globally Thalidomide was one of the most successful prescription drugs. The British pharmaceutical company Distillers produced Thalidomide for morning sickness where it was distributed throughout the British Isles, Australia and New Zealand under the trade name of Distavel, the advertisement reading: 'Distavel can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child...Outstandingly safe Distavel [Thalidomide] has been prescribed for nearly three years in this country'. Throughout Britain, Australia and New Zealand it was also prescribed as a tranquilliser under the trade names of Valgis, Tensival, Valgraine and Asmavel.

    (ix)In April 1961 Australian Dr W.G. McBride at Crown Street Women's Hospital, Sydney, notified the representatives of Distillers in Australia about his suspicions of the link between Distavel (Thalidomide) and malformations: Distillers in England claim they never received the written report. Sales promotion of the drug was stepped up and a quarter of a million leaflets distributed saying Thalidomide is 'Harmless even over a long period of use' and 'completely harmless even for infants'.
    On 4 May 1961 Dr McBride reported further malformations due to Thalidomide and succeeded in convincing his superiors that the drug must be withdrawn from use in the hospital. In October and November 1961 Dr McBride reported further malformed babies.
    On 27 November 1961 Thalidomide was withdrawn from the British market. On 16 December 1961 Dr McBride's observations were published in the Lancet, and in the Australian Medical Journal on December 23. On 6 January and 3 February 1962, Prof. Widijung Lenz who had warned against Thalidomide in Germany published evidence of deformities in Lancet.
    Only when the evidence was overwhelming did Chemie Grünenthal finally take Contergan (Thalidomide) off the market. However, in other countries around the world including Brazil, Italy, Japan, Sweden and Canada, drugs containing thalidomide were not withdrawn until a year or longer after Grünenthal's withdrawal of the drug.[2]
    By the time the drug was banned, more than 10,000 children had been born with major thalidomide-related problems. A common pattern of limb deformities, termed phocomelia from the Greek word for 'seal limbs', emerged including shortening or missing arms with hands extending from the shoulders, absence of the thumb and the adjoining bone in the lower arm and similar problems with the lower extremities. The drug also caused abnormalities in the eyes, ears, heart, genitals, kidneys, digestive tract (including the lips and mouth), and nervous system.

    (x)On 4 March 1962 Thalidomide was removed from the shelves in Germany because of public opinion and against the wishes of Chemie Grünenthal. News of the dangers of Thalidomide was played down by the media and in many cases malformed births occurred after the drug was withdrawn as mothers still possessing the drug, used it because they were unaware of the risks involved. At the time that Thalidomide was withdrawn in Germany thousands of malformed babies had been born, thousands of women required extensive psychiatric treatment and there were many suicides.
    The actual number of malformations that Thalidomide caused to babies can never be precisely assessed in the official casualty figures as in many of the poorer countries 'monster babies' and 'freaks', as they were deemed, were locked from view or destroyed by distraught parents who accepted the terrible afflictions as 'visitations from the devil'.

    (xi)In a statement at the Canadian Thalidomide Hearings, Prof. John B. Thiersch, Director of the Institute of Biological Research and Profesor of Clinical Pharmacology in the University of Seattle stated: 'In the ten years preceding the appearance of Thalidomide not less than 25 compounds were shown by various investigators ranging from Japan to the United States, to England and France, to affect the foetus in utero, either killing many foetuses or inducing malformations. The findings by the various investigators were published in scientific journals and distributed internationally'.
    But a more critical and greater universally-recognised fact had been ignored in the production of Thalidomide - of which the serious anti-vivisectionists will not need to be reminded: the safety of the drug had been based on the assumption that the principle of testing on animals is bona fide. A fact that is known to be incorrect, e.g., writing in his book Drugs as Teratogens, J. L. Schardein observes: 'In approximately 10 strains of rats, 15 strains of mice, 11 breeds of rabbits, 2 breeds of dogs, 3 strains of hamsters, 8 species of primates, and in other such varied species as cats, armadillos, guinea pigs, swine and ferrets, in which thalidomide has been tested, teratogenic effects have been induced only occasionally'...[3]

    (xii)More evidence of the avarice of pharmaceutical companies arose at the Thalidomide trial when clinical investigator Dr Jung who had received regular monthly payments for testing Grünenthal drugs stated that Contergan had proved to be an excellent sedative. When questioned at the trials about a report in which he had written that he had 'stopped administration' of the drug in three cases because of side-effects, Jung declared that the expression 'stopped administration' was badly chosen. In fact he had merely reduced the dose. During an hour-long interrogation of Jung the latter declared: 'I think you are under the impression that medicine is an exact science. You are quite wrong. A doctor has to take many decisions on the basis of experience and intuition'. And presumably also on the basis of financial encouragement received from the pharmaceutical companies.....

    (xiii)During the lengthy trial of the manufacturers in 1970, numerous court witnesses, all animal experimenters, stated under oath that the results of animal experiments are never valid for human beings.
     One of these experts was the Nobel Prize winner Sir Ernst Boris Chain who co-discovered the anti-bacterial effects of penicillin. According to the court records on 2 February 1970 he stated:

No animal experiment with a medicament, even if it is tested on several animal species, including primates, under all conceivable conditions, can give any guarantee that the medicament tested in this way will behave the same in humans: because in many respects the human is not the same as the animal.

     Because they had performed the required animal safety-tests, and because these did not show evidence of any danger, the manufacturers of Thalidomide were found not guilty by the court of consciously marketing a harmful drug.
    This of course is the real danger of animal experiments. Firstly, they can be manipulated, whether consciously or unconsciously, to produce results favourable to a financial backer. Secondly, they serve as a legal alibi for corporations when their products kill and injure people. It is worthy of note that Professor S. T. Aygun, a virologist at the University of Ankara, who used the so-called 'alternative' (non-animal) methods, discovered the danger of Thalidomide to humans and Turkey was spared the tragedy.
    It was also disclosed at the trial by Dr Muckter, the director of the scientific laboratory of Chemie Grünenthal, that all the company's records were destroyed - or had 'disappeared' during 1959....

    (xiv)After decades passing, the nightmare drug responsible for over so many human birth deformities continues to rear its ugly head with the appearance of its dreadful effects being passed on to the children of the victims. This latest threat of the possibility of further litigation against the makers of thalidomide has once again rallied industry-beholden animal researchers to the drug's defence with laboratory data 'disproving' the clinical findings.
    In the British Sunday Mirror of July 3 1994, ('Thalidomide dad's tragedy'), it was reported that the babies of six young men who were born deformed because of thalidomide have also been born with malformed limbs. Two of the babies have almost identical deformities to their fathers. Obstetrician Dr William McBride, whom first warned against thalidomide in 1961, has called on doctors to study children of victims and report back to determine the scale of the tragedy. He says there are second generation victims in Germany, Japan and Bolivia as well as Britain.[4]

    (xv)Despite all the clinical evidence to the contrary, British health authorities such as the Medical Research Council maintain that the vast bulk of evidence from laboratory and animal tests is against thalidomide having any genetic effects. In fact, thalidomide apologists still adhere to the defence that the thalidomide tragedy could not have been predicted, mainly because the drug had not been tested specifically for birth defects before being marketed, as at the time it was not required by law.
    Some argue that the thalidomide tragedy was not an example of an animal-tested drug which proved disastrous for humans, but of the dishonesty and sharp practices of the pharmaceutical industry. This view is based upon the fact that the animal tests carried out by the inventor of the drug, the West German pharmaceutical company Chemie Grünenthal, were very superficial and incomplete, their clinical trials were hastily done and questionable,[5] and that prior to the introduction of thalidomide Grünenthal did not carry out animal tests specifically to demonstrate teratogenic (malformation causing) effects.
    However it is evident that the human birth deformities caused by thalidomide was the result of misleading results from animal experimentation as well as the dishonesty of drug companies. The original animal tests by Chemie Grünenthal did not show indications of side-effect,[6] and furthermore, in several European countries, including England and Sweden, the licensees of thalidomide carried out their own animal tests, independently from the German firm, but still arrived at the same results as Chemie Grünenthal.

    (xvi) In reality, the accusation that the tragedy of thalidomide only occurred because of insufficient animal testing can be shown as nonsense. From 'Animal experimentation: A failed technology' by Dr Robert Sharpe:

'While it is true that thalidomide had not yet been tested specifically for birth defects prior to marketing, a close analysis of the tragedy suggests that animal testing could actually have delayed warnings of thalidomide's effect on the foetus.
By June 1961, Dr W.G. McBride, an obstetrician practising in Sydney, had seen three babies with unusual malformations and had strongly suspected thalidomide. To test his suspicions, McBride commenced experiments with guinea-pigs and mice but when no deformities were found, he began to have doubts that were to nag him for months (Sunday Times. Insight Team 1979).
    Then, late in September came further malformed babies and McBride became certain that thalidomide was responsible. He wrote to the Lancet and the Medical Journal of Australia and published his findings (McBride 1961). Further experiments revealed that even if thalidomide had been tested in pregnant rats, the animals so often used to look for foetal damage, no malformations would have been found. The drug does not cause birth defects in rats (Koppanyi and Avery 1966) or in any other species (Lewis 1983), so the human tragedy would have occurred just the same.
    According to the Catalogue of Teratogenic Agents (Shepard 1976): 'several...principles were forcefully illustrated by observations made of the outbreak. The first point was that there existed extreme variability in species susceptibility to thalidomide'. The Catalogue reports that by 1966 there were 14 seperate publications describing the effects of thalidomide on pregnant mice yet nearly all reported negative findings or else a few defects which did not resemble the characteristic effects of the drug. Only in certain strains of rabbit and primate can thalidomide's effect on the human foetus be reproduced.
    Teratogenicity tests have particular problems which make the results even more difficult to extrapolate to humans than other animal tests. In addition to the usual variation in metabolism, excretion, distribution and absorption which can exist between species, there are also differences in placental structure, function and biochemistry (Panigel 1983). Foetal and placental metabolism, and the handling of foreign compounds, are different in different species, and the use of several species does not necessarily overcome the problem. The difficulties are highlighted by aspirin, a proven teratogen in rats, mice, guinea-pigs, cats, dogs and monkeys, yet despite many years of extensive use by pregnant women, it has not been linked to any kind of characteristic malformation (Mann 1984).

Victims of vivisection: Thalidomide infants.

    (xvii)Ironically, as a consequence to the thalidomide tragedy there has been a marked upsurge in the number of animals used in the testing of new drugs. Drugs are also now specifically tested on pregnant animals to supposedly safeguard against possible teratogenic effects on the human foetus. The vivisector claims that if such tests were carried out prior to thalidomide's release, birth deformities in humans would have been discovered. This of course is sheer nonsense. As Dr Robert Sharpe observes: 'In pregnant animals, differences in the physiological structure, function and biochemistry of the placenta aggravate the usual differences in metabolism, excretion, distribution and absorption that exist between species and make reliable predictions impossible'.[7]

    (xviii)In fact when the link between human foetal abnormalities and thalidomide was established (through clinical observation), the world-wide explosion of animal testing, using a large range of species, proved very difficult to duplicate the abnormalities.
    The massively increased use of test animals following the thalidomide tragedy only served to dupe the public, encouraging it to keep consuming animal tested drugs. Consequently malformations are increasing. Over twenty years later, on July 19, 1983, a headline in the New York Times revealed: 'Physical and mental disabilities in newborns doubled in 25 years'. More recently, the March of Dimes Birth Defects Foundation, an organisation responsible for monitoring birth defects, reveals that every year more than a quarter million babies (1 in 12) are born with birth defects in the United States.
    In West Germany's authoritative medical journal Munchner Medizinische Wochenschrift, 1969, Dr W. Chr. Muller of the nation's First Gynaecological University Clinic reported that an extensive survey by German doctors had revealed that 'for 61% of all malformed children born alive and 88% of all stillborn children the intake of various drugs had to be held responsible'.[8]
The scientist J. McCredie reported that the limbs of children with thalidomide malformations show changes analogous to those which can occur in the adult as a consequence of pathological alterations to peripheral nerves.[9]

    (xix)The thalidomide tragedy is unusual as it is one of the rare occasions when both pro- and anti- vivisectionists claim that the incident validates their argument. Anti-vivisectionists assert that the animal testing failed to provide a warning of how thalidomide would affect human beings (thereby proving the uselessness of vivisection), while pro-vivisectionists claim that insufficient testing was conducted and if enough testing had been carried out, this would have indicated the danger of thalidomide.
    As is to be expected, the pro-vivisectionist's claim is nonsense. As Dr Greek notes:

As the incidences of deformity increased, scientists frantically attempted to reproduce teratogenesis [malformation] from thalidomide in animals of all varieties. They gave thalidomide to scores of animals looking for proof in animals of what they already knew occurred in humans - that thalidomide could cross the placenta and drastically damage unborn offspring - and they could find none. Since animal testing had not indicated a problem with thalidomide, its use persisted. Hence animal testing delayed the recall of this highly teratogenic [malformation-causing] drug.
Finally, one breed of rabbit, the White New Zealand rabbit, was affected, and then only at a dose of between 25 and 300 times that given to humans. Eventually some monkeys gave birth to hideously deformed offspring too, but it took ten times the normal dose to make this happen.[10]

Two scientists summarized the thalidomide testing as follows:

An unexpected finding was that the mouse and rat were resistant, the rabbit and hamster variably responded, and certain strains of primates were sensitive to thalidomide developmental toxicity. Different strains of the same species of animals were also found to have highly variable sensitivity to thalidomide.[11]

As already noted above, James L. Schardein wrote: 'In approximately 10 strains of rats, 15 strains of mice, 11 breeds of rabbits, 2 breeds of dogs, 3 strains of hamsters, 8 species of primates, and in other such varied species as cats, armadillos, guinea pigs, swine and ferrets, in which thalidomide has been tested, teratogenic effects have been induced only occasionally'. Elsewhere he wrote:

It is the actual results of teratogenicity testing in primates which have been most disappointing...while some nine primates (all but the bush baby) have demonstrated the characteristic limb defects observed in humans when administered, the results with 83 other agents with which primates have been tested are less than perfect...
Of the 15 listed putative human teratogens tested in primates, only eight were also teratogenic in one or more of the various species...the data with respect to 'suspect' or 'likely' teratogens in humans under certain circumstances were equally divergent...[12]

    Thus, pro-vivisectionists would have us believe the absurd proposition that it would have been possible for researchers to somehow predict the dangers of thaldomide from eighty-three agents, fifteen suspected human teratogens and nine monkey species and data too divergent to use. Sadly, while researchers continued with animal experiments, a further 10,0000 children were born, crippled and deformed, until thalidomide was finally withdrawn.
    Two pro-vivisectionists, J. H. Botting and Adrian Morrison stated in the Scientific American (February 1997), that 'scientists never tested thalidomide in pregnant animals until after fetal deformities were observed in humans'. This, according to Dr Greek is 'a gross misstatement' as animal testing was already the established protocol and their statement is unlikely to be correct, even at face value. In fact, according to a German medical journal, toxicity testing was conducted on animals before the release of thalidomide. [13] While it is controversial whether tests directly related to teratogenicity were conducted, there are indications from Germany that tests, specifically related to birth malformations, were conducted.[14] In view of this, the pro-vivisectionist's attempt to use the thalidomide tradegy as a support for vivisection completely fails.[15]
    Of course tests to determine the likelihood of malformation would have merely added to the confusion and uncertainty as researchers would not have known which animal actually reproduced the likely effect in humans, i.e., mouse, rabbit, guinea-pig, or primate, and furthermore, what dose was required to achieve this. As Dr Greek observes, 'administration of any drug to any species will at some juncture eventually induce birth defects'.[16]
    As Prof. George Teeling-Smith comments:

With thalidomide, for example, it is only possible to produce specific deformities in a very small number of species of animals. In this particular case therefore, it is unlikely that specific tests on pregnant animals would have given the necessary warning. The right species would probably have never been used. Even more striking, the Practolol adverse reactions have not been reproduced in any species except man.[17]

    Thus, it becomes obvious that even if much more testing had been done, including tests which included pregnant animals, researchers would not have been able to predict the tragedy of thalidomide in human beings. In sum, if all drugs were generally tested on a large number of animals species, sooner or later all drugs would have to be discarded as there will always be a species that manifests an adverse reaction. For example, aspirin is teratogenic for mice, rats, guinea-pigs, and some apes, and toxic and teratogenic for cats. Even caffeine is teratogenic for mice, and cortisone is teratogenic for mice and rabbits. In sum, by extending animal experimentation all that would happen is finding at least one species in which damage occurs.
    After the thalidomide disaster, thalidomide was found to cause malformations in the newborn of only a few animal species. If pro-vivisectionists wish to claim that this supports their argument, then they need to show how researchers would have been able to somehow know that the few animals were in fact the most accurate model for human thalidomide usage. And they also need to explain how the researchers would have known that all those many animal species in which malformations did not occur were not accurate models. They may also like to explain why, if the drug was not tested on pregnant animals, it was advertised as 'harmless for the pregnant woman and the foetus'.
    There is the further point that Thalidomide is known to be effective in treating systemic lupus erythematosus and severe forms of acne. However, animals do not suffer from either condition so it would appear that this information did not arise from animal experimentation but through clinical (human) studies: this is yet another example of the worthlessness (and danger) of vivisection.
    There is only one example of where the dosage of thalidomide given to laboratory animals is dealt with, quoted in a book by expert witnesses at the Alsdorf trial; this refers to mice being given half a gram of thalidomide per kilo of body weight, that is, a dose 600 times greater than was given to humans. Obviously any harmless substance will be toxic when introduced invasively in such ludicrously enormous and unrealistic doses.
    Professor Hugh Lafollette and Associate Professor Niall Shanks comment on how thalidomide 'successfully negotiate[d] the then current battery of animal tests', it was found that 'animals could tolerate massive doses of the drug without any ill-effect' and the researchers 'inferred the drug was safe for humans'. Of this they remark: 'They were of course wrong - more than eight thousand children were born crippled ordeformed'; and go on to say:

No animal tests had been done on pregnant animals. This leads defenders of animal experimentation to argue that the thalidomide disaster in no way shows that animal research is flawed [and if anything, it shows more research is needed]. As it turns out, this fact is of little solace to animal experimenters since what researchers would have learned from such tests, had they been conducted before the human epidemiological data, is not at all obvious. After all, the drug has since been shown not to produce detrimental effects in several strains of pregnant rats, mice and other mammals.[18]

    (xx)In sum, an objective analysis of this affair can only conclude that animal experimentation was responsible for the thalidomide tragedy, and furthermore, it continues to cause birth defects in human beings.
    Faced with the overwhelming evidence that the misery and suffering from thalidomide arose through animal experimentation, the only, somewhat feeble, defence now offered by vivisectors is that this tragedy could not occur again as current safeguards would ensure that it would be detected. Firstly, this fails to grasp the fundamental feature, i.e., that animal experimentation is worthless for revealing the effects of drugs on human beings. Secondly, the supposed safeguards will only be proved to be adequate if there is no repeat of a thalidomide-type tragedy. Considering what is at risk, and that the 'safeguards' are only there due to the erratic/unreliable results of animal experimentation, this merely shows a total disregard for human wellbeing and proper scientific methodology. The thalidomide tragedy shows that the only plausible 'safeguard' is no longer using animals to test drugs.

    (xxi)As a passing observation, it should be noted that on 22 June 1971 Australian Dr William McBride (see (ix) above) was invited to Paris by the Institut de la Vie where 18 Nobel Prize winners gathered to pay tribute to the man who alerted the world to the dangers of Thalidomide. In a ceremony he was presented with a gold medal and a prize of $40,000 (with which he established an institute for study of the first 41 weeks of life). In 1969 he was made a Commander of the British Empire and in 1977 awarded the Order of Australia.
    In 1972 after being named Father of the Year, Dr McBride created another international furore by announcing that Imipramine, a widely-used anti-depressant, caused birth deformities (The Australian Drug Evaluation Committee rejected the evidence). In 1980 turning his attention to the Debendox anti-nausea drug produced by Merrel Dow he appeared as an expert witness for the U.S. women who had children with birth defects and were sueing the manufacturer. The drug was subsequently removed from the market. There were many Debendox victims in Australia and New Zealand. Then McBride said his research showed that Debendox was also responsible for causing mental retardation.
    On 12 December 1987 McBride was accused of scientific fraud, of manoeuvring the results of the Debendox experiments. In November 1988 he was found guilty by a committee of inquiry and appealed against the decision. In an interview with Australian Good Weekend,[19] he accused the N.S.W. Health Department of being a 'Gestapo State' and said 'There's big money behind this', adding 'You know, big business is just as vicious as the CIA. Because I've given evidence for the kids in America... The drug companies have been known to resort to drastic methods to discredit those who appear in court against them'.
    In view of how McBride was treated after exposing yet more drug side-effects, it is hardly surprising that physicians are unwilling to do anything against the tide of conventional established thought. It should be noted that McBride had no anti-vivisection tendencies: in fact he was a fully-fledged vivisector. At its peak his Foundation 41 employed 16 researchers. However, the laboratories are now empty, and the meeting rooms closed; because of his insistence that drugs are dangerous to the unborn child (remembering that all these drugs are tested on animals beforehand) and his courage in challenging the assertions of drug manufacturers, Dr McBride is now isolated.

    (xxii)One of the more bizarre features of this matter is that researchers are now looking at the notorious drug as a potential treatment for certain severe or life-threatening diseases that do not have other treatments, e.g., leprosy, lupus and AIDS.
    In the early 1960s, an Israeli dermatologist, Jacob Sheskin claimed that thalidomide was effective in treating a particularly disfiguring form of leprosy called erythema nodosum leprosum (ENL). Thalidomide was approved in 1998 by the Food and Drug Administration (FDA) for the treatment of ENL.
    NB. Common side effects are said to include: fatigue, constipation, skin reactions, and peripheral neuropathy.
    Not surprisingly, thalidomide victims and those with first-hand experience of the tragedy are protesting at the idea of thalidomide being widely distributed again. Several internet websites deal with this and I repeat most of the comments made in one of these, below.

23 March 1998. Horror Approaches Again. By Jackie Alan Giuliano

History is an easy thing to ignore. Through ignorance and greed and, sometimes, just plain inexperience, much suffering has been caused by industrialization and technology.
Making a mistake once - or even twice - can often be forgiven. But when greed is allowed to run rampant and rationalizations are made to the horrors of history, the gap between our minds and our souls widens.
The front page of the March 26, 1998 Los Angeles Times carries an article about the U.S. Food and Drug Administration's plan to approve the use of Thalidomide again. This move will spell the beginning of a genetic nightmare that even those sponsoring the action admit to.
Dr. Cynthia Moore, of the U.S. Centers for Disease Control, said at a conference last fall that, "If thalidomide is made available in the United States, it will be used by women of childbearing potential, and babies will be born with thalidomide birth defects."
FDA official Dr. Debra Birnkrant said "It's probably true, unfortunately." Yet approval appears imminent. Sadly, even the head of the thalidomide survivors organization is helping them write the warning labels...

As spring envelopes the Northern Hemisphere and the wildflowers bloom, the U.S. Food and Drug Administration is recommending that the obscene and deadly drug, Thalidomide, be approved for use again. They say it is to treat a complication of leprosy, a rare, but curable, disease that affects 2 million people throughout the world. They say that it can give relief to sufferers of AIDS and cancer.
But at what cost to our future and to our children? On Saturday, September 6, 1997, the Los Angeles Times had a small article about this on page 6, at the top of a page dominated by a mattress sale. In the San Diego Union Tribune, it was on page 8. The story said the FDA is recommending 'tightly controlled' use. Today, March 26, 1998, it is on page one of the L.A. Times. Approval seems imminent.

Thalidomide was developed in the 1950s in Germany, first as a sedative and then widely used as a pill to ease morning sickness. But soon, thousands of babies were born without arms or legs or with flipper-like feet. Some had only a head and torso. In many cases, the pregnant women took only 1-100mg pill, often borrowed from a friend.
Between 1958 and 1962, over 12,000 babies in 48 countries were born terribly deformed. The L.A. Times article casually states that "the drug was never sold in the United States because an FDA scientist uncovered early signs of toxicity and blocked approval. Still, some Americans got it overseas or in clinical trials." What they didn't tell you was that 3,000 Americans were given the drug between 1958 and 1962 as part of a marketing study! At least 9 Thalidomide children are the result of that giveaway. The lies and deceptions run deep in our world....

There are 8,000 survivors of Thalidomide in the world today. There are 3,000 in Germany, 1,000 in Europe, and others in Japan, Asia, and Latin America. There is a small group of 230 in Brazil who are still fighting today for compensation and recognition. Brazil is an example today of Thalidomide use out of control.
In 1993, over 8 million Thalidomide tablets are manufactured per year in Brazil and over 10,000 tablets per year in South Wales in the United Kingdom. Thalidomide is being used to treat not only the side affects of leprosy drugs, but in Britain it is widely used to treat a condition that results in terrible mouth ulcers in AIDS and non-AIDS patients. It has even been used to treat back pain in Britain. In the U.S., it is being studied as a treatment for tuberculosis. Since its worldwide withdrawal (it was never really "banned") in 1962, Thalidomide has been quietly coming back. The Brazilian and British governments claim that the use of the drug is tightly controlled and the World Health Organization has even recommended its use. Yet A&E's Investigative Reports program found many Thalidomide children in Brazil, some as old as 21 years!
Many doctors worldwide say that there are alternatives to Thalidomide and that there is no excuse for using this deadly drug. But the officials who approve such things never venture into the slums or the Amazon rain forest where the drug is terribly abused.
A&E found many tragic cases throughout Brazil of pregnant women who were given Thalidomide by their doctors and who felt they were not adequately warned. Well-meaning husbands who were being treated for their own symptoms and didn't understand gave their pregnant wives the drug. One of these cases was a 9-year old boy, born without legs, his mother given the drug by a doctor. She receives no money at all for her son's disability. Another victim, a 21-year-old woman, rarely ventures from the leper colony where she lives in Brazil.

In a small town in Brazil, 9 year old Michele waits at the bus stop to go to school. The driver passes her by because she has so much trouble getting onto the bus with her artificial legs - they do not bend.

In the Amazon rainforest, Thalidomide is given out freely...Officials say that distribution of the drug is tightly controlled. A&E sent a 23 year old woman into one of the local wholesale pharmacies that carries Thalidomide. The woman, accompanied by a hidden camera, was sold three bottles of 10 tablets each of Thalidomide with no prescription. And to make matters worse, the bottles had badly worded warnings in English only - the woman spoke only Portuguese. I am enraged that the U.S. FDA could come to such a reckless conclusion. We must work together to stop this horror. Many Thalidomide survivors had hoped that their generation would be the last - an example of medical science gone mad. They had hoped that lessons would be learned. Some even support the release of the drug in a vain attempt to find meaning in their senseless struggles. It is so ironic that the very drug that resulted in tighter control of drugs and serves as the shining example of medical folly is back - in a big way.

References
[1]R. Sharpe, The Cruel Deception: The Use of Animals in Medical Research, Thorsons, 1988, pp.105-106.
[2]H. Sjostrom and R. Nilsson, Thalidomide and the Power of the Drug Companies, Penguin Books, 1972, pp.131-48.
[3]Rep. in Drugs and Pregnancy-Human Teratogenesis and Related Problems, ed. by D. F. Hawkins, Churchill Livingston, 1983.
[4]'Thalidomide horrors show up in the children of victims', Gold Coast Bulletin, Australia, April 26, 1995.
[5]Sjostrom and Nilsson, p.191.
[6]Sharpe, p.106.
[7]Sharpe, p.107.
[8]W. Muller, Munchner Medizinische Wochenschrift, No.34, 1969.
[9]J. McCredie, 'Thalidomide and congenital charcot's joints', Lancet, 1973, vol. 2, pp.1058-61.
[10]Dr C. Ray Greek, and J. S. Greek, Sacred Cows and Golden Geese (London, Continuum, 2000), p.45. Sources: Exp. Mol. Path. Suppl., 1963:2, pp.81-106. Federation Proceedings, 1967:26, pp.1131-1136. Teratogenesis, Carcinogenesis, and Mutagenesis, 1982, vol. 2, pp.361-374.
[11]J. Mason and D. Wise in Casarett and Doull's Toxicology, 4th. edn (McGraw-Hill, 1993).
[12]James L. Schardein, Chemically Induced Birth Defects (Marcel Decker, 1985). J. L. Schardein, Drugs as Teratogens (Cleveland: CRC, 1976), p.5.
[13]Arzneimittelforschung, 1956:6, p.426-430.
[14]Ibid.
[15]Dr C. Ray Greek, and J. S. Greek, Sacred Cows and Golden Geese (London, Continuum, 2000), p.46.
[16]Greek, pp.46-47.
[17]Prof. George Teeling-Smith, A Question of Balance: the Benefits and Risks of Pharmaceutical Innovation, p.29. Pub. Office of Health Economics, 1980.
[18]Hugh Lafollette and Niall Shanks, Brute Science (London: Routledge, 1996), pp.14-15.
[19]The Sydney Morning Herald Magazine, 15 July 1989.

The Ghost of Medical Atrocities: What's Next, After the Unveiling?
By HOWARD MARKEL, M.D.
http://www.nytimes.com/2003/12/23/health/23ESSA.html

Ever since 1972, when the American public first learned about the Tuskegee syphilis research that subjected African-American men to scientific experiments without their consent, the medical profession has had much explaining to do about its past.

Since then, several disturbing instances have come to light. In those cases, scientists, physicians and the government-sanctioned research or treatments that we would today consider unethical, like trials of untested vaccines or medications on mentally retarded children and prisoners.

Increasingly, public apologies have been made to smooth over these clinical transgressions. Yet the doctor in me wonders whether these gestures will cure what ails us.

Since 2002, five states - Virginia, Oregon, North Carolina, South Carolina and California - have publicly apologized to people who were forcibly sterilized under laws in effect from the early 1900's until the 1970's. Thirty-three states enacted such laws in this period, and about 60,000 women and men were sterilized. All were deemed "unfit to reproduce" by the medical experts of the day.

When these sterilization laws were written, many subscribed to a simplistic version of genetics called eugenics and hoped to improve American society by encouraging the "healthy" to reproduce while simultaneously preventing those with "deleterious inherited traits" from doing so. Under this rubric, mental retardation, insanity and even criminal behavior were considered hereditary and the "carriers" of these traits a danger to future generations.

Sadly, those targeted for reproductive quarantine were already defined as outcasts by a white majority: the mentally ill or retarded, "sexual deviants," the impoverished, African-Americans and immigrants.

The recent series of public apologies for forced sterilizations has unfolded with markedly different results, depending on who did the apologizing and the motives of the person or group.

In March, with no survivors on hand to hear it, Gray Davis, then the governor of California, issued an apology for the 20,000 forcible sterilizations conducted in his state. In contrast, the previous December, Gov. Michael F. Easley of North Carolina not only made a meaningful apology to the families of the 7,500 victims of his state's mandatory sterilization laws, he also ensured that their stories would be remembered by creating a
special historical archive. And last month, Dr. William Applegate, the dean of the Wake Forest School of Medicine apologized for his institution's involvement in these forced sterilizations.

Some activists are now eager to broker a formal apology from Gov. Jennifer Granholm to the 3,700 people sterilized in Michigan. But Alexandra Minna Stern, a historian of medicine at the University of Michigan, said the issue was far deeper than merely uttering words of contrition.

"The biggest danger of the public apologies is that they too readily allow us to blame our predecessors as being scientifically misguided or evil and pat ourselves on the back for an enlightened, morally informed present," she said.

Thankfully we have moved out of an era of heavy-handed, coercive sterilization statutes, but many of the era's ethical issues remain. Today, there is a great risk of societal pressures more subtly influencing reproductive choices thanks to an ever-expanding repertoire of genetic reproductive technologies, therapies and prenatal genetic screening tests.

Dr. Paul A. Lombardo, a bioethicist at the University of Virginia, worked successfully last year with his state's Legislature to commemorate Carrie Buck, a young woman sterilized against her will in 1924 after eugenics field workers diagnosed her, her mother and, by assumption, Carrie's 7-month-old daughter, Vivian, as "feebleminded." Ms. Buck's case was contested all the way to the Supreme Court where Justice Oliver Wendell Holmes Jr. famously opined, "Three generations of imbeciles are enough."

Although there is a symbolic value to apologizing for the sins of our fathers, Dr. Lombardo admits that these "are limited ways of addressing public harms done in the past."

Reflecting on her experience as a member of the citizens committee that convinced President Bill Clinton in 1997 to apologize for the government's role in the Tuskegee syphilis experiments, Susan Reverby, a historian at Wellesley College, said: "There needs to be more than a television talk show format of confession and a pledge for repentance. Relying only on emotion, while critical and cathartic, is a temporary fix, at best."

These apologies would be far more meaningful if they prompted us to reflect on some troubling aspects of medical research financed by federal agencies and American pharmaceutical companies in developing countries today, like experimental drug trials in Africa, where there are markedly less strict regulations on patients' rights.

Perhaps the cruelest aspect of such trials is how comparatively little these federal agencies or companies do to ameliorate or prevent the scourges that are killing Africans and others by the tens of thousands every day. AIDS, tuberculosis, malaria, measles and diarrheal diseases are all major killers that we can actually do something about now. Decades hence, will our successors conclude that the impulses that nurtured experiments like Tuskegee or public health policies like eugenic sterilizations simply moved offshore in the early 21st century?

The stunning advances in medical progress have created new problems as we begin to dissect exactly how we arrived at some of this lifesaving knowledge. But after-the-fact apologies are soothing balms, not panaceas.

One of the greatest emerging ethical challenges in medical practice, research and policy goes well beyond identifying missteps based on human blind spots or outright prejudices embedded in past quests for cures. We must make sure we don't repeat them.

Copyright 2003 The New York Times Company

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