Thalidomide

The History

"In June 1956 [Aldous] Huxley wrote an article in the Sunday Times of London observing that Homo sapiens had been taking mind-altering drugs since prehistory- especially alcohol, of course. "Will the pharmacologies be able to do better than the brewers and distillers?" Huxley wondered. "It seems reasonable to suppose it." "
An executive at the British pharmaceutical firm, Distillers Company (Biochemicals) Ltd., read Huxley's article and promptly pointed it out to the company's director, E.G. Gross, in a memo the next day. "The ultimate target," he wrote, "would be the production of the ideal tranquilizing agent to replace alcohol among those people who would prefer to 'transform their minds' by this alternative means." ...
The very same week, Chemie Grünenthal offered Distillers Company an opportunity to license thalidomide for manufacture and distribution in the United Kingdom. From the way it was described by the German company that had invented it, this new sedative was the dream drug for thee Utopian market that chemical companies around the world were aiming to conquer." (p.5)

"That was ground zero for history's greatest medical tragedy. Based on the contemporaneous practices of other drug manufacturers, the company should have conducted cautious, investigative human trials with thalidomide- including its impact on pregnant women. Just since 1949, in countries around the world, twenty-five compounds had been found that killed or deformed the fetus, establishing the need for such trials. In 1953, for example, the results of the human trials of cortisone in pregnant women were published, noting any malformations in their children at birth. Such a study of thalidomide would have limited the tragedy to a few individuals. Instead of conducting a methodical investigation, the Grünenthal team simply distributed free samples through doctors, without any monitoring or follow-up, to judge from the little evidence that remains. They even handed out pills to their employees. As one observer put it, "Thalidomide was introduced by the method of Russian roulette. Practically nothing was known about the drug at the time of its marketing." Exactly why the Grünenthal men acted so irresponsibly remains, at best, a subject for speculation; but the damaged medical world of postwar Germany- the "cradle of thalidomide"-suggests that the lingering callousness of medicine under the Third Reich played a role." (p.10)

Marketing Thalidomide

"Thalidomide was first sold in a drug called Grippex, which contained thalidomide quinine, vitamin C, phenacetin, and aspirin. It was marketing on a limited basis for treating respiratory infections in Hamburg in November 1956.
On October 1, 1957, thalidomide was first released as a sedative under the patent name Contergan. Because of its unambiguous claims of safety, thalidomide was sold over tyhe counter in Germany, and later in other countries as well. The marketing campaign was massive, Grünenthal advertised the drug in fifty medical journals, sent out 50,000 "therapeutic circulars," and mailed 250,000 personal letters to individual physicians, emphasizing the drug's safety. The main thrust of the campaign was that, unlike other sedatives currently on them market, thalidomide was completely safe. Even a determined suicide could not take enough Contergan to cause death. Furthermore, accidental overdoses by children would be unheard-of with this drug, a claim later substantiated by actual cases that were widely publicized by the company.
The marketing campaign was highly successful, and over the next three years sales grew steadily. By 1961, thalidomide was the best-selling sedative in Germany, with total sales of DM 12.4 million, five times more than its leading competitor, Doriden." (pp.14 -15)

Dr. McBride & Thalidomide

"On the other side of the world, another story was beginning to unfold. On August 18, 1960, Walter Hodgetts, senior New South Wales sales representative for Distillers Co. Biochemicals (Australia) Ltd., met with Dr. John Newlinds, the medical superintendent at Women's Hospital, Crown Street, Sydney. He was there to persuade the hospital to try Distaval (thalidomide), a sleeping pill that had already been on the market in Britain for two years. Hodgetts left a bottle of Distaval tablets with Newlinds, who in turn sent it on to the hospital pharmacy. During his sales rounds, Walter Hodgetts visited Dr. William McBride, who ran one of the largest obstetrics practices in Australia. McBride agreed to try Distaval as a sedative for his patients in labor, little knowing how this encounter would alter the course of his life, for better and for worse.
Two weeks later a woman came to the Crown Street Hospital emergency room. She had been vomiting for several days, and nothing that anyone tried could stop it. She was two months pregnant, and the physical effort of vomitting was so severe that it threatened to cause a miscarriage. Since all other medications had failed, Dr. McBride decided to try the new drug, and the patient stopped vomiting. McBride was impressed. The medicine appeared to have considerable promise for obstetric patients, and that package insert stated that it was perfectly safe, even during pregnancy. So McBride began to prescribe Distaval to patients who complained of morning sickness, nervousness, or insomnia." (p. 22)

The Trial of Thalidomide

"In May 1968, after six years of legal investigation into Grünenthal tactics in marketing thalidomide, the West German Ministry of Justice opened the criminal trial of nine executives of Chemie Grünenthal, including Mückter, Kunz, Keller, and Hermann Wirtz...
In all, there were 2,866 known German victims represented in the trial; a separate, more moderate group had settled out of court with the pharmaceutical company. After enormous planning and preparations to deal with traffic, lodgings, and the like, the trial began on May 27. The indictment alone was 972 pages long, based on 500,000 pages of documentation, including many seized in police raids on Grünenthal's "bunker" when executives did not comply voluntarily.
The strategy of the defense appear3ed to be a war of attrition: to exhaust the opposition and the rest of the court, and, at he last moment, to make the best possible settlement, without ever admitting guilt. Their arguments and tactics were so heinous it is hard to be the had the gall to put them forward...
Probably the most unforgettable argument put forward by the inventors of thalidomide was that all the babies' deformities were the fault of the mothers themselves, from botched attempts at abortions. And though it seems unbelievable, they offered an even more grotesque and far-fetched theory. One Professor Kloos from Berlin testified for the pharmaceutical corporation that thalidomide did not cause the fetus to be malformed; instead, he explained patiently, thalidomide had actually salvaged the lives of deformed fetuses that otherwise would have naturally miscarried. Grünenthal's expert was arguing that the "victims" were actually living abortions who had been saved by the drug...
The first medical expert that was called was....Professor Widukind Lenz... The defense asked the pediatrician if it wasn't possible for the defects to have been caused by some unidentified virus, [and] Lenz observed that "a virus would not stop at the Berlin Wall, "a reply that baffled the defense attorneys, who hadn't even though of that...
The prosecution set about to prove that Contergan caused nerve damage and fetal malformation. Perhaps their best argument for the former was the fact that Grünenthal had admitted to paying out significant sums to neuropathology victims; but they also had testimony from many who hadn't recovered in seven years. As for malformation, the proof was multifaceted and undeniable. To begin with, a graph of Contergan sales matched exactly- almost spookily- the recored births of deformed babies, with exactly a nine-month lag. So when sales dropped dramatically owing to reports of nerve damage, so did the number of deformed infants. And there had not been a single case of phocomelia reported in Germany since months months after the warning went out. Three hundred and fifty witnesses slowly hammered home the same message.
Meanwhile, Grünenthal's heavy handed techniques continued, inside the courtroom and out. In May 1970, as the trial went into its third year, at least five journalists complained to the court that representatives of the company had threatened them with reprisals for what they had written. By this time, the defense had warned the victims' families that the trial ... was delaying a civil settlement that would give the families the money they needed; and they went further. Grünenthal made an offer, tied to a threat: they would put up $27 million for the children, but if the trial continued they would fight to the end in civil court....
No guilty verdict was every rendered, no personal responsibility was ever assigned, and no one went to prison. Since that was Grünenthal's goal all along, the company could boast they had won their war of attrition, and they did. They still do. The non-verdict in Germany is a source of lasting bitterness and grief to all the victims and their families. There was some consolation. The court did at least find that "a causal relationship has been proved" between thalidomide and nerve damage, and "there can be no doubt about the teratogenic properties of thalidomide in man, which were discovered by Professor Lenz...." And the judges firmly emphasized that Mückter and his colleagues were neither being acquitted nor exonerated. The trial was simply being discontinued "in the public interest". " (pp. 71-77)

Thalidomide and HIV/AIDS

"One of the most promising discoveries [Dr. Gilla Kaplan] made in the mid-1990s was that thalidomide stimulated T-cell production vary dramatically in test tubes, by somehow triggering the immune system's complex signaling system, making for more and more of the immune "cammandos" to fight off infections. She did not know how this came about biochemically, but it seemed extraordinarily promising. When administered to patients, however, the results were much less positive, and in some patients with advanced HIV infection (AIDS), conditions worsened with the drug. At first, there was some hope that this was a "paradoxical reaction," which means specifically a response to a drug in which the condition initially worsens before improving. But these patients continued to deteriorate, and were taken off thalidomide...
Among the many symptoms in HIV patients, thalidomide remains useful almost exclusively for aphthous and esophageal ulcers. The drug is now one of the lesser weapons in the new armory of medicines." (p. 160)

- from Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine by Trent Stephens and Rock Brynner (2001)

Related Articles:

Distaval Advertisement
Thalidomide Child
Thalidomide in the British Museum
ShareThis