Introduction

Published by the American Anti-Vivisection Society, Suite 204, Noble Plaza, 801 Old York Road, Jenkintown, P.A. 19046-1685, U.S.A., 1986.

Since publication of An Introduction to the Study of Experimental Medicine by the famed physiologist Claude Bernard in 1865, both the public and the medical community have been taught that animal experimentation is the key weapon in the war against disease. Bernard's book should go down in the annals of public relations history as among the most effective promotional publications ever printed. The French physiologist's goal was straightforward: to convince the physicians of the late 19th century that laboratory physiology was not simply the occupation of addle-headed tinkerers in academic departments. Clinical investigation - the direct study of actual human patients - had long dominated medical science; it was Bernard's intention to hypnotize the nineteenth century clinicians into defying their own common sense. In "Divided We Stand: Physiologists and Clinicians in the American Context," Gerald L. Geison writes:

"When the great French physiologist Claude Bernard began to lecture on the medical significance of experimental physiology, he lamented over the number of physicians who believed that "physiology can be of no practical use in medicine", that it was "but a science de luxe which could well be dispensed with." It was presumably in an effort to change this attitude that Bernard wrote his famous Introduction to the Study of Experimental Medicine ... To Bernard it seemed obvious that "solid instruction in physiology ..., the most scientific part of medicine", was precisely the one thing that physicians most needed.

Nonetheless, physiologists were not taken seriously in the U.S. until well into the twentieth century and were often confined to departments of philosophy rather than medical schools. While the genuine achievements of animal research were few and far between (primarily the development of anti-toxins, antibiotics and vaccines), laboratory physiology rapidly became the key to academic advancement for ambitious medical students between 1930 and 1950. The incentive to promote the value of laboratory physiology for human medicine became even more powerful during the early twentieth century with the growth of agencies established to fund medical research. With the birth of the National Institutes of Health and its vast financial resources, the battle for research grants encouraged laboratory physiologists to greatly exaggerate the actual contribution of animal research to advances against human disease. From roughly 1930 on, medical students were taught that virtually every significant advance - from the discovery of insulin to surgery for "blue babies" - arose from "basic" scientific research on laboratory animals. These distortions were further propagated by the corporations that proliferated with the rise of animal experimentation: the laboratory-animal breeders, sellers, and promoters. While occasionally a brave clinician dared to contradict the dogma of animal experimentation, he did so at grave risk to his reputation and his livelihood. Mass media stories continued to aggrandize the accomplishments of animal research, and even investigative reporters failed to see that the claims of animal researchers were largely a promotional device aimed at bringing in the federal funds.

Today, the inexorable public relations campaign begun by Claude Bernard is more vigourous than ever. While clinicians and epidemiologists have yet to effectively communicate the fact that virtually every major advance against human disease has been achieved by direct study of human patients, basic scientists continue to mesmerize the medical community, the public and the federal funding agencies. Of all the laboratory physiologists and animal researchers who have attempted to influence the direction of American medical research over the past three decades, few have had so profound an impact as the renowned physiologist Dr. Julius Comroe. There is no greater champion of basic laboratory research in modern history. During the Johnson Administration, Comroe began an extensive investigation of some 10,000 scientific articles to determine how the major advances against heart and lung disease between 1945 and 1975 had been achieved. From his research, Comroe concluded that basic laboratory research (much of it on animals) was critical to many of the major advances against heart and lung diseases. During the debate that raged over the value of basic research and whether it should be heavily funded by the federal government, Comroe was the most vocal spokesperson for basic scientists. His testimony was undoubtedly among the major factors influencing Congress' decision to increase the support for basic medical research during the late 1960s and early 1970s.

One of the few clinical investigators to contradict Comroe during that time period was Dr. Robert A. Good, former director of Sloan-Kettering Cancer Institute and now of the University of Oklahoma School of Medicine. Good, who ranks among the most respected clinical immunologists in the world, took issue with Comroe's criticism of the surgeons who had performed the first successful heart transplant in human beings. Comroe's criticism - that the surgeons failed to explain to the public that the transplant procedure was only made possible by decades of basic laboratory research (much of it on animals) - was widely reported in the mass media. On the other hand, Good's answer to Comroe, published in an issue of the Journal of Clinical Investigation, got no media attention at all. During the 60th annual meeting of the American Society of Clinical Investigation, Good delivered a landmark presidential address in which he explained that both insulin and heart transplantation were in fact triumphs of clinical investigation. Good said: 

"Another example of how little this role of clinical investigation is understood in historical or contemporary perspective is revealed by a recent indictment of the transplant surgeons. The indictment was directed against the cardiovascular surgeons who electrified laity throughout the world with their heart transplantation. This leading basic physiologist [i.e. Comroe] focused on the failure of the cardiovascular surgeons in national and international publicity deriving from their adventure to recognize contributions from the basic sciences which to that viewer had made possible the technical contribution of heart transplantation. A number of examples were cited in which basic contributions had paved the way for heart and organ transplantation. Included were such major advances as development of the science of circulatory physiology, control of infection, development of anesthesiology, pharmacological support of cardiovascular function, technological progress permitting secure diagnosis, control of immune rejection, and others. From my somewhat prejudicial position, I seemed to hear a dramatic recitation of example after example in which investigation [of actual human patients] had led the way, asked the critical questions, established the incisive view, or had dipped, even prematurely, into the methodology of basic and enabling sciences. Certainly the control of infection is in great measure attributable to leadership of clinical investigators. As examples one can cite Semmelweis and Holmes who independently interpreted natural clinical experiments correctly; Lister, already a clinical investigator who was alert to the earliest unestablished reports from Pasteur; and a host of clinical investigators, some still in this room, who established the safe and effective use of chemotherapeutics and antibiotics in clinical medicine.

"The discovery and application of anesthesiology, to me, also derives from interpretations of several natural experiments and conduct of critical clinical investigations. The professional physiologists have contributed much to the understanding and control of the circulation, but was not the discovery of the circulation of the blood primarily an interpretation of a clinical experiment of nature? I think so. 

"The discovery of the foxglove, the first of the cardioactive pharmacologicals, was made as the result of a natural clinical experiment. Establishment of the credibility of this insight, too, was the function of a most precise clinical investigation. 

"Finally, it seemed to me that the application of certain poorly-understood antimetabolites or cancer chemotherapeutic agents for immunosuppression has launched the transplantation era. Was this not the audacious manipulation by a young clinical hematologist, now a member of our Society, who had achieved a vector from clinical and experimental forces? We must not only understand and insist on proper support of the basic and enabling sciences, but we must insist that the fruits of clinical investigation are real..."

Despite the insistence of clinical investigators such as Good, Comroe's most recent book, Exploring the Heart, an easy-to-read account of the evolution of techniques for the diagnosis, treatment and prevention of cardiovascular disease, implies that many if not most advances against heart disease were achieved by means of animal experimentation.(5) Because Monroe's book will likely be so widely-read, the author decided to write the present monograph, Heart Research on Animals; A Critique of Animal Models of Cardiovascular Disease. The purpose of this monograph is simple: to criticize the animal models in current use and to assess which advances are due to animal experimentation and which to clinical investigation. For the purposes of this monograph, an "advance" will be defined as a model of treatment or prevention that is either shown effective in well-controlled randomized clinical trials (RCTs) or is so dramatically effctive that RCTs are unnecessary. The RCT - in which the effectiveness of a new treatment on patients is compared to placebo - is now recognized as the "Gold Standard" for judging the effectiveness of new treatments. Despite this well-known fact, Comroe does not use RCTs to judge the effectiveness of new procedures. Instead, Comroe relies on completely unscientific "expert opinion" to determine which developments constitute an "advance". Comroe himself writes: "To avoid bias, we decided to ask physicians, who were in no other way connected with our study, to list what they considered to be the most important clinical advances since 1945 that were directly responsible for diagnosing, preventing or curing cardiovascular or pulmonary disease, stopping its progression, decreasing suffering or prolonging life."

It should be obvious to anyone familiar with modern scientific principles that Comroe's definition of an advance is without any scientific basis. Nonetheless, for the sake of completeness, the current monograph explores the history of the research that led to "advances" against cardiovascular diseases, using both the definition of "advance" in this monograph and those advances cited by Comroe. Those innovations that are cited by Comroe's definition and by objective scientific evidence from controlled trials will be so indicated by a star (*) on the cover page of the chapter. For the sake of brevity, the current monograph omits a detailed discussion of diagnostics. The reader is referred to the excellent accounts of the development of diagnostics for cardiology in M. Beddow Bayly's Clinical Medical Discoveries.

Has animal experimentation led to significant advances against human cardiovascular disease? Do the animal models of hypertension, stroke and coronary artery disease closely simulate the diseases of actual patients?

The answers may surprise many readers.

Foreword