Dark Remedy, The impact of Thalidomide and its revival as a vital medicine.
by Stephens and Brynner, Perseus, 2001, 216 pages, with table of contents, bibliography.
I could not put it down. This is very readable, for someone familiar with the FDA, medico-legal jargon. Dark Remedy is presented as a factual history of the life cycle of the drug thalidomide. Since it is a history, I don’t think I can give away the plot by summarizing the story. The plot is like something out of Stevenson’s Dr. Jekyll and Mr. Hyde, wherein a brilliant physician finds an elixir, which seemingly is a wonder drug, a magic wand, and is so hailed throughout Europe, the English commonwealth, and South America. But, a lowly government bureaucrat in the FDA refuses to pass on the wonder drug. The bureaucrat is denounced. Curmudgeon! Obstructionist! Surprisingly, some learn the magic wand actually spreads death and destruction in its wake. The official is praised. From zero to hero! Suddenly, the physician, after maiming many patients, bans and buries the very memory of the poison. Lawsuits follow, but, as no good deed goes unpunished, the settlements leave victims impoverished to become street beggars or promiscuous. However, still fascinated by the elixir, new uses are found until it rises again, like the Phoenix from the ashes, for treatment in hundreds of rare diseases.
“Poison or Panacea?”
The purpose of this review, and my recommendation, is not to focus on Thalidomide. The drug could just as easily have been named Coumadin. For those unfamiliar with Coumadin, it is the drug name for a chemical which lowers the blood clotting ability. Blood clotting is the body’s defense against leaks. If your blood could not clot, any rupture, tear, hole, puncture, cut, could be life threatening as your fluids would drain out, like a hole in the radiator of a car, until the engine overheats and is destroyed. Coumadin can be a killer. In fact, rice soaked in Coumadin has been used as an ingredient in rat poison. Except for Mickey Mouse, who is a mouse and not a rat, rats are on the low end of society’s esteem. Rats have two things going against them, they sneak around at night and gnaw and eat through paper, card board, and plastic to get into food, and they breed rapidly. So, the mechanism of Coumadin is to be eaten by the rats, and then when the females reproduce they will bleed to death, if they haven’t already done so by scratches or cuts received in their life style. And if the Coumadin rice is unintentionally or unfortunately eaten by people or pets, remedies can neutralize the anti-clotting factor, which will speedily pass out of the system. Coumadin can be a life saver. As blood clots after surgery can lead to strokes or death, Coumadin can reduce the risk of unwelcome clots, and is thus prescribed to heart and by-pass patients. Truly, “One man’s poison is another man’s pleasure.”
When Walt Disney started drawing animated characters, a story goes, he reasoned he could save time and money by having the cartoon people have only three fingers and thumb on a hand, instead of four fingers. Perhaps the audience wouldn’t notice, or if they noticed, wouldn’t care. Thus in Disney’s Laugh O-Grams, circa 1922, the girl and boy have four fingers, but by 1923’s Alice in Wonderland, the characters (dogs, cats, and mice) have three fingers. See Disney from Mickey to the Magic Kingdom. The audience accepted the fantasy that Mickey and Donald and Goofy and the rest had three fingers, and Disney saved whatever sums one less finger per hand cost in paying artists to draw and paint cells by the hundreds of thousands for the movies. Disney seemed to have great success with threes and so named several movies, such as “The Three Little Pigs,” and “The Three Caballeros,” and others.
In the mid 1980’s, I shook hands with a businessman, a real estate broker, outside Cleveland Oklahoma, and noticed he had three fingers and a thumb on each hand. Just like a Disney cartoon. Perfectly formed fingers and hands, but nothing I had seen before, except in a cartoon. I asked how he came to be three
fingered? He said his mother took Thalidomide when she was pregnant. He was born with the three fingered hands. The expectant mother took a drug which was not approved for American use. Boy, was he lucky he only lost a finger on each hand.
United States Food & Drug Administration reviews clinical trials.
Dark Remedy is an excellent introduction to United States Food & Drug Administration, popularly known as the ‘FDA’. The FDA is an agency within the Department of Health and Human Services. FDA evaluates clinical trials and testing. You really appreciate the FDA approval process.
The thalidomide story relates to the effort to get medical recognition. Briefly, the Pure Food and Drug Act of 1906, which created the FDA, was passed in response to fantastic claims made by merchants selling medicines which may or may not have worked, and some of which were dangerous for human consumption. Under the Food, Drug and Cosmetic act, as I understand it, if you claim anything is safe, therapeutic, cures, prevents disease or injury, you have to be able to prove it and get it certified by the FDA. The present set of laws for approving drugs, medical devices, and systems are directly the result of the Thalidomide story.
The pre-story began in Germany in the latter nineteenth century. Germany had some brilliant chemists, such as Kekule who discovered the benzene ring Germany was also the home of Diesel, and Bayer, the manufacturer of aspirin. Thus, German chemists had great prestige.
Some post World War II German chemists synthesized and found a compound which had sedative properties and seemed to have no toxic dose. It was a drug looking for a disease. Eventually it was observed it could be a tranquilizer to replace barbiturates, which were fatal in overdose. Thus was thalidomide developed to treat depression. It seemed the wonder drug of tranquilizers. It was claimed to be safe and tested. It had been tested, mostly to find the level of toxic dose. Nevertheless, it was not safe. But, supposedly it did not have the side effects of other drugs. It did soothe nausea (vomiting, sickness at the stomach), a common symptom of pregnancy.
When offered to America, the FDA officer in charge of its review, Dr. Francis Kelsey, refused immediate approval. The expert endorsements were simply based on the European experience, i.e. that it had been distributed for four years in over forty countries. But the data for clinical trials, testing the claims, was nearly non existent. New York Times 1962 July 16th (page 24,
col. 3). The American drug company licensee, anticipating early and speedy approval, manufactured tons of the pills, and distributed tens of thousands of free samples under the guise of American clinical trials. These were not trials, as little, few, or no records were kept of which physicians received the samples, or to whom the physicians gave the drug. Some physicians or patients in America received the drug from the American licensee, with patients probably unaware it was without FDA approval. The licensee held no trials, but did reapply with more expert opinions. While waiting for the trials to report, the FDA officer disregarded the licensee’s clamor to make the drug available. The ‘expert opinions’ coincided with the era of using actors, dressed in white lab coats, with stethoscopes around their neck and endorsing cigarettes by the score.
Within a year, by 1962, reports began to circulate of a rash of malformed babies in Europe. A certain percentage of babies will have deformities, depending on the problem. The number may be one in hundreds of births, or thousands births. The deformed babies born in Europe, had little stump arms or leg buds, a medical condition of phocomelia. The normal rate was one in four million. They were now being born at rates many thousand percentage points above previously expected rates. The search was on for the reason. Eventually it was strongly suspected that Thalidomide caused the birth defect. Other than wide spread distribution, it had not been clinically tested for pregnant women. It damaged the developing fetus. It killed about a third. The FDA had spared disaster, or at least heart ache, for tens of thousands of American families, by the caution of one. The FDA’s success reinforced the belief that the European government drug regulators don’t operate at the same level of care as expected in America. Because they don’t.
Dark Remedy gives a very stimulating and interesting analysis of the medical epidemic, which is the first one fourth of the book, and the analysis of the litigation and regulation, which, in the aftermath, is the remaining three fourths.
Parallels of interest.
There are some parallels in the thalidomide and carpal tunnel syndrome stories. First, both affect women in disproportionate numbers. Only women become pregnant and will incubate birth defects, and eight of ten Carpal Tunnel Syndrome, (herein CTS) patients are women.
Second, both received none to minimal clinical trial study. When distributed by prescription and over the counter in Europe, Thalidomide had only been tested for toxic doses, as to how much was required to kill half the test animals, mice usually. That none died, only lead to the suspicion from Dr. Kelsey that the rats were not even absorbing the drug, but that it was passing through altogether. Neither did the rats become sleepy or sedated. However people were sedated, which meant people were absorbing it. The lack of any controlled clinical trials was her first reason to ask for more data. Similarly, as of 1997, the FDA office of Restoratative devices advised that no clinical trials had been offered for carpal tunnel syndrome before the
Finger Relief protocol. Without tests, what do you really have? Guesswork.
Third, both affect the nerves, beginning with the finger tips. Thalidomidedoes have a measurable side affect in that, within a few months in a significant number of users, it caused permanent nerve damage. The damage begins with tingling in the finger tips and toes, and gradually moves up the arms and legs. CTS sufferers also report damage beginning with tingling and
numbness in finger tips.
Fourth, both can be deadly. A third of the thalidomiders, babies with birth defects, did not survive. There is at least one case wherein a Woman whose tactile sensation in her finger tips has been damaged by CTS, could not as reliably or effectively use breast self examination for early detection of tumors or cancers.
Fifth, both evils were met with skepticism. The manufacturers of thalidomide denied its danger and fought lawsuits for decades. As did tobacco companies. Attempts have been made to refuse CTS injuries status for workers compensation. CTS victims have been greeted as a malingering, or with derision, contempt and levity by business, and at the highest levels of government (i.e. the U.S. Supreme Court).
Sixth, both have a disfunctional relationship. As stated in Dark Remedy, thalidomide was a remedy looking for a disease. CTS is an injury looking for a remedy.
Seventh, both CTS and thalidomide research were underfunded. Dark Remedy teaches a lesson about the effort it took, at the grass roots, to get government, medicine, academia, and business, to study the thalidomide problem. It took about three decades after discovery before money was available for sustained research. Thalidomide competed with many other compounds for research grants. CTS research has not been similarly under funded. It competes with many other diseases.
Eighth, both thalidomide and CTS looked to surgery for a convenient remedy. The thalidomide remedy for birth defect was abortion, and Dark Remedy sketches the beginning of the pro-abortion movement from a couple seeking a therapeutic abortion in Arizona due to thalidomide induced birth defects. Another thalidomide surgical remedy, after birth, was to cut off the stubby flipper legs or arms, leaving the victims quadraplegics. CTS’s last stop remedy is carpal tunnel release which has become the most common hand surgery in America with estimates in the late 1990’s running at four hundred thousand per year. Of course, after the release, cutting the dorsal carpal ligament, if CTS returns, there is no further treatment, except to stop using the hands and do something else.
Ninth, both are little understood. Thalidomide’s mechanism for causing birth defects was not studied for years. Even now, the mechanism for interfering in the embryonic development is theoretical. CTS, part of Repetitive Stress Injury or herein as RSI, is apparently so poorly understood that it was hailed as being solved by OSHA regulations in 2001 which, in fact focused on the sedentary jobs of truck drivers, according to the press releases from OSHA. In RSI, the “S” stands for stress, not sedentary.
Tenth, in both, litigation has been the excuse to prevent progress and research. For thalidomide, the German criminal case prevented experts who were testifying in Germany, from giving testimony in cases in other countries, or raising public awareness of the disaster. At the same time, once the lawsuits
started in England, for a decade the London newspapers were forbidden to discuss the thalidomide epidemic, and warn of its use for people who already had the pills before they were recalled. For CTS, the keyboard litigation has been cited by attorneys for the workers’ compensation carrier for defendant keyboard maker’s as the reason to not fund any testing of keyboards as it may relate to safety or CTS.
Eleventh, in both, government’s response to action is to pass a law or obtain agreement and declare the problem solved. For thalidomide, a foreign government, through its prosecutors or officers, pressured victims to settle claims, even though the amounts were under the government’s own inadequate estimates. For CTS, the passage of the Americans for Disabilities Act, and OSHA regulations have solved the problem, which of course won’t go away, as more CTS cases arise every month.
Twelfth, in both, claims of safety, or implied safety, were used to market products to get gain. For thalidomide, the German, then English and American licensees, claimed the drug was safe for pregnant women, and dozens of other categories of patients, and diseases. For CTS, because of FDA regulations restricting the use of safety, the marketing for keyboard, mouse, monitor and other computer peripherals, use terms meant to imply safety. Such terms include “natural” or “ergonomic” or “alternative,” so selected in order to stay within the law, to wit: avoid the word ‘safety’. The terms mean nothing.
Thirteenth, in both, antiquated technology exacerbated the recovery of patients prevention of injury. For thalidomide, to mask the embarrassment of the little flippers and arm or leg stubs, the children were fitted with expensive, but useless, heavy and even dangerous, artificial arms, legs, and hands (prosthetics). Consider at page 112;
“[mechanical arms] ridiculous . . looked like
a robot . . . totally unfunctional . . .
couldn’t do anything in them really . . .
totally useless . . . couldn’t pick anything
up with them. Very, very impractical and they
were extremely heavy, … caged in… [legs]
were worse, because they were far more
dangerous – extremely heavy … design hadn’t
been changed since the First World War . . .
made of cast-iron and plaster … didn’t have
the balance with having no arms … you fall
to the ground … constant fear … fall
forwards or backwards … fall on me face or
have stitches in the back of me head.”
Among keyboard sufferers of CTS, the QWERTY typewriter keyboard, even more antiquated than the above prothesis, has been around since the days of Custer’s last stand. Consider these:
“awkward … designed to slow typing”  –
“worse possible arrangement”  –
“confidence tricks” [or scam] Century of the
Typewriter,  – “very poor”  – “wrong
thing”  – “costly … error … slows …
produces fatigue”  – “inefficient”  –
“not the best … [makes] much more work” 
– “not superior.” .
Fourteenth, both affected tens of thousands without knowing what happened. For thalidomide, many patients were not told they were in a clinical trial for an untested drug. For CTS, sufferers can’t get reliable information on clinical trial, There are very few trials, and if there were, none were reported. As recently as 2005, a survey of the National Institute of Health’s abstracts for reports and clinical trials searching for comorbidity of a patient having breast cancer and carpal tunnel syndrome returned no such studies or abstracts out of two and a half million indexed reports. None out of 2.5 million.
Fifteenth, both had reports of danger hidden or ignored. For thalidomide, even while the drug was sold over the counter, without prescriptions, reports of dangers and problems were given to the distributor, the distributor’s employees and officers lied about the reports, lied about tests, and hid the negative reports from the medical community, government, researchers, and patients. For CTS, a 1995 independent research report funded by the Health and Human Services, which found the Finger Relief and Dvorak keyboards safer than QWERTY, was ignored by OSHA, Occupational Safety and Health Administration, and NIOSH, National Institute for Occupational Safety and Health, in later keyboard studies, and by the NIH, National Institutes of Health, in later grants.
If you want to read a book to expand your information on medical research, and how the drug or medical device approval process works, read this one. If you want a book which gets you to thinking, read this one. If you want a story which makes you thank your lucky stars, read this one. I enjoyed it.
Cites for Notes
 Quantification of Tendon Excursion &c, Flannery, Robertson, and Cooper, Conference Proceedings, 19th Annual Meeting of the American Society of Biomechanics, August 1995, p. 195;
 Typists’ Speed & Efficiency, Virginia Russell, Computer Technology Review, Winter 1985;
 Wilfred A. Beeching, New York: St. Martin’s Press, 1974, pp. 14 to 47;
 Illustrated World Encyclopedia, Vol. 14, 1970, Glen Cove, New York, p. 4694;
 interview in Conquering the Keyboard, by Robert Alonso, Personal Computing, August 1985, p. 72;
 United States Patent 3,847,263, 1974, column 1, U.S. Patent and Trademark Office;
 United States Patent 4,655,621, 1987, column 1, USPTO;
 1994 Compton’s Encyclopedia, Typewriter, p. 342;
 See “The Case Against QWERTY” at National Museum of American History, Smithsonian Institution, Wash. D.C. 1992, p.39.
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