ANIMAL EXPERIMENTATION: THE MEDICO-LEGAL ALIBI

- Dr André Menache, speaking at the 10th World Congress on Law and Medicine, held at Jerusalem, Israel on 29 August, 1994.

Although animal experimentation can be traced back as far as Galen (ca. 100 AD), its significance in medical research and consumer safety is a relatively recent phenomenon. In 1865, Claude Bernard published his INTRODUCTION TO THE STUDY OF EXPERIMENTAL MEDICINE, which marked the beginning of animal experimentation as a "scientific method" of research.

This paper attempts to challenge the scientific validity of the "animal model" theory, and to examine the natural consequences of such a theory with respect to medical research and consumer safety.

Depending on the funding source (e.g. competing sectors within the same industry), animal experiments can be used to prove, or to disprove, almost any theory. Given the large variety of laboratory animals available today, and the multiplicity of laboratory conditions under which these experiments are carried out, it should not come as a surprise.

Industry has always been quick to exploit the less-than-conclusive results of animal tests, especially in the field of cancer. Thus, saccharin remains on sale to the public because it appears to cause bladder cancer only in male rats! The injectable contraceptive "Depo-Provera" was banned in the U.S. over 20 years ago on the basis that it caused cancer in dogs and baboons. Yet the FDA (Food and Drug Administration), America's health regulatory authority, recently unbanned the drug because 20 years of human experience in those countries which did not prohibit its use had convinced the FDA that "Depo-Provera" did not cause cancer in humans. An even more bizarre example is that of the drug "Tamoxifen", used to treat human breast cancer. Although Tamoxifen reduces the incidence of mammary cancer in rodents, it actually increases the incidence of liver cancer in rodents, and would appear also to be nephrotoxic.

Despite the fact that thalidomide represents a tragic chapter in medical history, and certainly an example of one of the worst clinical disasters, its manufacturer (Chemie Grunenthal) was acquitted in December 1970, at the end of the longest criminal trial in Germany's judicial history. In the book SUFFER THE CHILDREN: THE STORY OF THALIDOMIDE (Futura books, 1979), the authors concluded that: "People injured by drugs are still almost in the same position as the thalidomide families: they are at the mercy of antiquated legal systems that assume that they have the money, knowledge and mental fortitude to fight for compensation. Science has moved quicker than law."

It may be possible that today the courts are beginning to comprehend the lack of scientific methodology underlying many of the basic assumptions in consumer safety, where animals are used as "protectors" of public health. This subject was reviewed in a paper entitled: "The erosion of acceptibility of animal toxicity tests in the courtroom", which was presented in November 1993, at the World Congress on Alternatives and Animal Use in the Life Sciences, held in Baltimore, U.S.A.

Over the years, there has been strong criticism also outside the courtroom. In an important editorial in Clinical Pharmacology and Therapeutics (August 1976), Dr Kenneth Melmon stated that: "In most cases, the animal tests cannot predict what will happen when the drug is given to man. Standards of toxicology are often set by officials, such as Federal regulators, who are responding to the pressures of ill-advised but obviously well-intended legislators or consumer groups who may or may not be aware of the futility of increasing the amount of testing required when some tests often have no bearing on how man will respond to the drug."

Because of irreconcilable biological differences between animals and human beings, the results of animal tests cannot be applied to human beings with any degree of confidence. Dr Ralph Heywood, past scientific director of Huntington Research Centre (U.K.), stated at a 1989 scientific workshop held at the Ciba Foundation that: "...the best guess for the correlation of adverse reactions in man and animal toxicity data is somewhere between 5% and 25%."

This data translates into unacceptable risk levels for the general consumer public. To illustrate this point, consider the fact that the General Accounting Office in the U.S. reported that between the years 1976 - 1985, of the 200 new medications introduced over that period of time, a full 51% were either withdrawn from the market completely or else re-labelled, because of severe side effects not previously noticed.

As far back as 1964, Dr James D Gallagher, Director of Medical Research at Lederle Laboratories, stated in the Journal of the American Medical Association that: "Animal studies are done for legal reasons and not for scientific reasons. The predictive value of such studies for man is meaningless - which means our research may be meaningless." This statement highlights the conflict between the regulatory need for animal tests in pre-clinical studies, and the scientific validity or relevance of such animal tests with respect to human beings.

Despite extensive animal testing designed to "safeguard the consumer public", tragedies continue to multiply, even in recent times. Upjohn's acclaimed sleeping pill "Halcion" was banned in the U.K. in 1991; silicone-gel breast implants, implanted into about 4 million women, are now under suspicion; Pfizer's Bjork Shiley heart valve was taken off the market in 1986, after more than 300 deaths were blamed on the device. Pfizer set aside $500 million to settle the claims. Bolar's generic dyazide pills for high blood pressure were found to be defective; the pills were recalled in 1990 and the company fined $10 million.

Time Magazine reported in July of 1993 that 2 of 20 U.S. participants in a clinical trial of the drug fialuridine (for the treatment of hepatitis B) died from an adverse drug reaction, while 9 others were hospitalised. Eli Lilly, the manufacturer, promptly stopped all testing in late June 1993. Similarly, the new antibiotic "Omniflox" produced by Abbot Laboratories was recalled from the market in mid-1992, following reports of severe adverse reactions including 3 deaths. The drug had been approved by the FDA in January of the same year.

To make matters worse, the FDA itself has been faulted on animal drug data. In a report to Congress in 1992, the General Accounting Office found that the Food and Drug Administration in many instances did not conduct inspections to verify the accuracy of data supplied by private laboratories, and that, because of the FDA's "inadequate procedures", the agency "may be unable to fulfill its mission to protect the health and safety of animals and people."

Dr Murry Cohen, past chairman of the MRMC (Medical Research Modernisation Committee) in the U.S., stated at the International Conference "Future Medical Research Without the Use of Animals: Facing the Challenge" held in Tel-Aviv in May 1990, that: "An awareness is growing that new methodologies are required to gain insight into important questions of human health and disease. Animal experimentation has not provided the hoped-for and much-needed answers to these vital questions."

Groups of medical doctors, like the MRMC, are now at the forefront of the scientific movement advocating that animal tests be replaced with new methodologies.

In addition to the invaluable contribution to medical science of clinical observation, autopsy studies, epidemiology, non-invasive scanning, and the like, we are now entering a new world of In Vitro technologies involving tissue and organ cultures. What is even more significant is the increasing availability of tissues of human origin, which will reduce the margin of error even further, as compared with extrapolating results from animal tests to humans.

If we were to simply sit back and "let nature take its course", it is likely that animal experimentation would be phased out gradually over the next 30-40 years. However, if we recognise the fact that animal tests are seriously misleading and contribute little to consumer safety, and we still do nothing, then we are all guilty, by sin of omission, for not hastening their demise.

Article reprinted from the DBAE newsletter, July/August 1994, and Dr Menache is President of DLRM.


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