From the Proceedings of the 2nd International Scientific Congress Against Vivisection, London, England, April 1991. Sponsored by DBAE (Doctors in Britain Against Animal Experiments)
The Process of Biomedical Discovery: A Historical Perspective
It so happens that I became a medical historian in a rather roundabout way. I had always been very fond of animals, and had been looking for an animal welfare issue that would hold my interest. When I entered veterinary school and began to learn more about medical science, I became more and more suspicious of the claims that had been made about the importance of animal experimentation to medical progress. I had grown rather tired of the empty ethical debates, carried on without any scientific background or context, about whether it is right or wrong to use a mouse in an experiment. I wanted to know whether animal experiments were actually useful for their intended purpose, and, if so, why they were useful. This led me to study the literature in the history and philosophy of science, as well to an analysis of a great deal of historical case material, in order to understand how and why animals were being used in medical experiments.
What I found flatly contradicts the government 'party line' that animal experimentation has led to virtually every major advance in the last one hundred years. On the contrary, I found that animal experiments had misled biomedical science time and time again. I found that they are not a means for generating medical discovery. I also found that most medical discoveries are achieved by doctors and surgeons who study human patients during life and at autopsy. The animal experiments are usually performed in order to convince skeptical colleagues of the validity of a discovery already made in a clinical context.
In my thesis of biomedical discovery, the initial stage in discovery is the generation of a "clinical hypothesis", and this initial clinical hypothesis derives from an anomalous clinical observation. For instance, in the early part of this century surgeons began to notice an odd form of lung cancer in men who smoked cigarettes. That anomalous observation led them to the clinical hypothesis that cigarette smoking causes lung cancer. In the late 1940s epidemiologists in the U.S. and U.K. undertook large human population studies to determine if the initial clinical hypothesis was correct. Based on this human data, it was, by 1950, clear that cigarette smoke usually causes lung cancer in human beings.
However, public health action against cigarette smoking was stalled for many years because researchers were unable to reproduce lung cancer in animals by blowing smoke down their windpipes. They tried smoke on guinnea pigs, rats, mice, chickens and other animals but were unable to induce lung tumours. So, the tobacco companies could argue that cigarettes were perfectly harmless!
Once I had gained confidence in my thesis of biomedical discovery, by testing it against case material in physiology, pathology, therapeutics, and prophylaxis, I decided that it was time to attempt my magnum opus: to try to understand how, in the 1840s, Claude Bernard managed to convince the medical world that animal experimentation is reliable as a means of biomedical discovery and testing. Bernard, the father of modern laboratory medical research, wrote "An Introduction to the Study of Experimental Medicine", and it is the 'Bible' of modern medical research.
By analysing Bernard's book and by going over every passage with care, I deduced that he had deliberately misattributed biomedical discovery in general, and his own discoveries in particular, to animal experimentation. He did this in an extremely subtle but highly effective way. I have, in fact, worked out how Claude Bernard was able to misattribute his own medical discoveries to animal experimentation. By writing An Introduction, he was able to pass on his fraudulent account of biomedical discovery to his successors in the animal laboratories.
Modern animal researchers have followed Bernard's erroneous rules to the letter. The main idea is to always claim to have made your discovery "by accident" . This allows the animal researcher to assert absolute priority of discovery. It is a way for him to claim that his discovery was not actually inspired by clinical observations -- though it invariably was inspired by clinical studies. Bernard always claimed that his discoveries were "born of chance". We now know that this is nonsense! Discoveries are no more made by chance than are rockets built by chance. In Bernard's case, his discoveries were made by reading of the human pathology literature. For example, his first major discovery was that the pancreatic juice breaks down fats. He claimed to have made the discovery during an experiment on a rabbit. In fact, the American historian Frederick Holmes examined Bernard's notebooks in search of proof that the celebrated animal experiment had taken place. There is absolutely no evidence that Bernard ever did the experiment! He apparently made it up in order to assert his own priority in the discovery. As I argue in the April 1991 issue of The Journal of Medicine and Philosophy, Bernard had actually made the discovery by reading about an "experiment of nature" -- a human case in which the pancreatic duct had been blocked by cancer. The patient had had extremely fatty stools throughout life because the pancreatic juice could not get into the intestine. Many similar case studies had been reported in the 1830s, but Bernard claimed to have made his discovery in the apocryphal rabbit experiment of 1848 -- many years after the initial clinical studies. I call Bernard's tactic "chronological inversion". He contends that animal studies lead to human studies, when in fact the opposite is the case: human autopsy studies are the actual source of inspiration and lead to attempts to 'confirm' the clinical hypothesis in animals! Because the animal laboratory produces such varied results, you can "prove" almost any hypothesis you want. The animal researcher who wants to plagiarise a discovery can always do so by claiming that he is the first to "prove" the discovery which till then had been "only dimly suspected" on the basis of human autopsy studies.
I feel that Claude Bernard's distorted account of biomedical discovery has had an extremely negative overall impact on the course of biomedical progress. There are three primary impacts:
- First, widespread "inter-additional plagiarism", by which I mean that animal researchers have been plagiarising physician investigators for many years by claiming to have "confirmed" what the physicians "merely hypothesised". People who make such claims know nothing about how hypotheses are actually tested in a biomedical context.
The second impact is that many of the major medical breakthroughs of the 20th century were delayed by as much as 50 years. I will discuss this later.
Finally, and perhaps worst of all, Bernard's account hinders the acceptance of major new biomedical theories which are based upon human, clinical evidence and not on animal experiments.
I suggested at the outset that the cigarette-cancer hypothesis was not taken seriously during the 1950s because it was based upon human, clinical evidence and not on animal studies. Since animal experiments are so much more dramatic than clinical studies, these were used (eventually) to "sell" the idea that cigarette smoking causes lung cancer in human beings. Researchers were unable to duplicate the human evidence until the late 1960s. At that time, researchers finally succeeded in producing a form of lung tumour in dogs by blowing smoke into their lungs. It had taken some 17 years to eventually find the "right" experimental set-up to reproduce roughly the human experience.
Another case in which animal experiments badly retarded the advance of medical achievement is bypass surgery. Widely touted as a breakthrough by animal research, bypass surgery was actually held back by many years because of misleading animal experiments. Nevertheless, the animal researcher Alexis Carrel is generally considered the founder of bypass surgery. It was, in fact, not Carrel but the French clinical investigator Jean Kunlin who pioneered bypass surgery in 1949 without any prior animal experiments. Kunlin was actually building on 200 years of clinical investigation of a rare "experiment of Nature" called Arteriovenous Aneurysm (AA). Patients with AA have veins that pulsate like arteries, and the veins bear up as if they were arteries. Thus, based on long study of the veins of AA patient, doctors prior to Carrel's time had concluded that human veins can withstand the relatively high blood pressure in the arterial system. Kunlin was aware of the clinical studies and determined to use a segment of the patient's own vein to bypass an arterial obstruction. It worked very well.
Unfortunately, American researchers then tried putting vein grafts into the arterial system of dogs. And what happened? The vein grafts ballooned into aneurysms. An illustration of this was presented to the 1952 annual convention of the American College of Physicians, and it created quite a stir. Such experimental results scared most American surgeons away from using the patient's own vein as bypass graft material -- which was eventually shown to be the best way to do bypass surgery of the leg and heart. Thus, misleading animal experiments actually delayed the development of bypass surgery for many years.
The development of kidney transplantation was likewise delayed for many years by misleading experiments on dogs. In the late 1940s and early 1950s, the leading dog experimenters in Britain, Simonsen and Dempster, argued that kidney transplants could not possibly work in human beings as the rejection reaction would be too violent. In fact, however, American surgeons in Boston, led by David Hume, decided to try such transplants in people because they reasoned that patients in severe kidney failure seemed to have natural immunosuppression, making them more likely to tolerate an implant better than healthy dogs. The team at Peter Brent Brigham (Hospital) ignored the animal data and tried the transplants in patients -- and the procedure worked for as long as six months, i.e., more than ten times as long as it had worked in dogs.
Another example of how animal experimentation can delay medical progress comes from the case of the polio vaccine. While that triumph is widely attributed to animal experimentation, in fact, misleading monkey experiments actually delayed application of the polio vaccine by more than thirty years. Simon Flexner, who performed the monkey experiments in 1911, was head of the Rockefeller Institute for Medical Research (and principal reorganiser of American medicine early in this century!), so his opinion had enormous weight. Flexner had blown the polio virus into the monkeys' noses, and on that basis concluded that polio is by and large a disease of the human brain and spinal chord. If you blow a virus into the nose, it will head straight for the brain. Because, then, the virus could only go directly to the brain, Flexner was forcing Nature to answer his question the way he wanted it answered. In act, from studies of children with polio, it was discovered that polio is largely a disease of the intestinal tract -- the virus does not usually go to the spinal chord to cause paralysis. Once researchers realized that the virus could be grown in the intestinal tract of the human being, they reasoned that the virus could be grown in intestinal tissue cultured in the test tube. That breakthrough allowed the cultivation of enough virus to be used for a mass-produced vaccine. It was John Enders and his team at Harvard that first grew polio in tissue-culture. That development made the monkey studies of polio completely obsolete. But the monkey experimentation had delayed the polio vaccine by thirty years.
As I mentioned earlier, Claude Bernard's distorted account of biomedical discovery has led to widespread plagiarism of physician investigators by animal researchers. A classic case is that of Philip Levine, who actually discovered the so-called "Rhesus factor" of blood cells but whose work was plagiarized by a monkey researcher. Levine made his discovery by studying a woman named Mary Seno in a New York City hospital. Seno had had a severe immunological reaction both to her unborn foetus (which was born dead) and to her husband's transfused blood. On that basis, Levine deduced that Seno's husband and foetus must have had an unnamed blood factor on the surface of their blood cells which was lacking in her's. But unfortunately, when Levine published the case in 1939, he did not name this blood factor -- and of course "he who names it claims it". That allowed the monkey researchers to busy themselves in attempting to duplicate the experience of Mary Seno -- in (Rhesus) monkeys. While they in fact failed to find the identical blood factor in monkeys, they named Levine's blood factor the 'Rhesus' or Rh factor. In this way Levine's clinical discovery was plagiarized by the monkey experimenters.
I predict that it will become more and more difficult for clinical investigators to win acceptance for new medical theories. The reason is that the theories are becoming more and more complicated, and it is becoming harder and harder to "confirm", or, more accurately, to "dramatise" a clinical hypothesis with an animal experiment. In such an experiment you can yank out an organ or 'laser-beam' a tissue, but you can't test complex medical theories. There are currently several major medical discoveries that are being resisted because they cannot be "proven" by animal experiments, though they are solidly grounded in clinical evidence. One example: the discovery that low-level irradiation of a parent can result in leukemia in the offspring -- even if the radiation is delivered prior to conception. This finding cannot be proven in animal experiments. Another example: a bold new theory of disease called the Mutagenic Theory of Chronic Diseases. The brainchild of Dr.Irwin D.J. Bross , this theory maintains that most cancer and heart disease actually result from environmental damage to human DNA. But it cannot be "proven" with animal experiments. And so -- as in the case of the cigarette-cancer theory -- it is steadfastly resisted by the biomedical establishment.
I hope this talk has clarified the reasons that I thought it necessary to understand the process of biomedical discovery and to lay to rest the notion that Claude Bernard's vivisectional method is a scientific method.
Thank you for your attention.
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