Animal Experimentation and the Red Queen 

During her travels in Wonderland, Alice met many unusual characters, including the Red Queen, who never stopped moving at a frenetic pace. As she explained to Alice, it takes all the running one can do to stay in the same place. The historical development and continued reliance on animal models as a cornerstone of biomedical research and testing shares a similar perspective as the crimson monarch. Researchers have been running with animal models of human diseases, injuries, psychopathologies, and risk assessments for more than a century. Despite self-serving claims to the contrary, most of these efforts have not been biologically or medically successful. In this case, by staying in the same place, researchers often overlooked more appropriate methods to solve important human and animal health problems. 

____________________

  The race has produced a few rare and useful discoveries. As with slot machines, if you pull the traditional levers enough times, a winner eventually appears. Most of the money and profits, however, go to the house not the patient.

There are dedicated scientists working to solve problems of animal and human health and welfare. The problem issue for animal advocates is not the researcher or the questions being asked. Rather, the concern is the tools being used to answer those questions. Increasingly those choices involve humane alternatives, but the traditional overemphasis on animal models continues. Interestingly, the current genetic engineering fad, alteration of the genetic composition of laboratory animals to more closely resemble human diseases, serves as proof that decades of non transgenic experiments relied on inappropriate animal surrogates. If the old style models were relevant, why the need to improve’ them?

 The image of the scientist searching For knowledge, guided only by objective .analysis of the facts, using the best tools available, is one of the great myths of our time. Biomedical researchers are basically no different than other members of society and are just as likely to stretch the facts, manipulate information, and act as irrationally as anyone else when under attack, defending a comfortable way of life or selecting 'models’ for their research programs.

By carefully examining the many areas of biomedical research that involve the use of laboratory animals, a consistent pattern of inherent biases is routinely observed. Their effect on the validity of the experiments ranges from mildly confounding to a complete negation of the results.

  In some cases, the experimental responses of a laboratory animal or a portion of his or her body may he so over-generalized that they no longer have any resemblance to biological reality. An experimental psychologist in Canada once told me that he could freely extrapolate data from artificial laboratory behavioral and surgical manipulations among all species of mammals because the different animals all had the same neurotransmitters. Thus, the evidence of species specific behavioral patterns, millions of years of evolutionary divergence, and both anatomical and physiological differences were dismissed as insignificant by reducing all of the species to simple bags of similar chemicals.

 Perhaps one explanation for the tendency to reduce biology to a study of parts of animals, animals divorced from their environments, or simplistic mix and match genetic manipulations, lies in the training most biomedical researchers receive, These individuals seldom have comprehensive backgrounds in the biological sciences, such as courses in animal behavior, botany, ecology or evolutionary theory. Do they really understand the behavior and biology of the species used in their experiments?

For example, it is relatively easy for some researchers to secure repeated

As with slot machines, if you pull the traditional levers enough times, a winner eventually appears.

funding for laboratory studies of aggression that have little or no meaning to either humans or non-humans, while scientists wanting to study aggression in natural, free ranging populations of the same animals have difficulty finding financial support.

 A corollary of biological reductionism is the failure of some biomedical researchers to recognize or appreciate that laboratory animals are not simply machines or little boxes that produce varieties of data. Once consideration of animals is reduced to this level, callousness and insensitivity to the animals’ pain, suffering, and basic needs can follow.

 The single experience that contributed most to my personal rejection of animal experimentation involved a foreign postdoctoral student whose animals were dying from neglect. When I discussed this problem with his supervisor, one of the most distinguished scientists in the department, I was told to “let all of his animals die, and when he loses his data, he’ll take it more seriously.”

For most current users of laboratory animal ‘models,’ whether in educational demonstrations, product development and risk assessment, or in non clinical basic biomedical research, there is a general inability to directly apply information derived from one species to another or even to themselves. The current emphasis on transgenic manipulations represents an artificial attempt to experimentally overcome this basic fact, ignoring the entirely new set of biases and problems associated such procedures. 

Laboratory animals are frequently used as surrogates for humans, although they may he biologically and or medically irrelevant to the specific problems under study. As originally conceived animal models were used to investigate infectious agents to which the animals shared vulnerability with humans, such as tuberculosis and polio. Since they are no longer realistically needed for that specific purpose because infectious diseases can now be identified, characterized, and studied more effectively in cell and tissue cultures (e.g., all of the early work on AIDS). animal models have consequently been shifted to situations in which they only mimic the human disease or health problems.

Today, animal models are seldom subject to the same causes, symptoms, or biological mechanisms as their purported human analogies. The widespread bias introduced by bogus animal models is a direct result of the failure to recognize, or a choice to ignore, the problems of interspecific extrapolations. Transgenic experiments may produce a horde of new publications and models, hut their relevance and reliability remain as questionable as before.

In their effort to secure research funds, expand the territorial boundaries and influence of their laboratories, or simply maintain their employment, it is a common practice for biomedical researchers to generate an endless series of experiments by devising minor variations on a common theme, redefining previous work, subdividing one problem into multiple parts, or manipulating new technology and equipment to answer old or irrelevant questions. Such practices are endemic in such fields as experimental psychology, substance abuse addiction, and most of the neuroscience and transplantation protocols.

 Although exact duplication of research projects is relatively rare, the level of similarity is often such that the experiments are essentially redundant. Replication of research results is a valid scientific principle. Redundancy and variations on a common theme (parametric tinkering), however, are simply bad science.

There is an unstated but pervasive status hierarchy within the biomedical sciences. It is the belief of many practitioners that working in a laboratory using sophisticated equipment and precise measurements is better science than the more traditional, non mechanistic, organismic investigations of such subjects as ecology, ethology, and epidemiology. Those scientists with the broadest experience in the biological sciences are often the least likely to engage in experiments involving laboratory animals. The prolaboratory bias has been characterized as physics envy. One of its most persistent manifestations is the need to rise laboratory animals to quantify, characterize, and manipulate the obvious. This type of bias should not be confused with the work of those researchers who develop and utilize in vitro technologies to answer legitimate biological and medical questions. 

 Biomedical scientists and funding organizations (public and private) often are influenced by an anthropocentric attitude that the closer an animal model comes to humans evolutionarily, the more relevant, fundable, and status laden the project becomes.

The most obvious negative impact of this evolutionary bias is that it prevents the use of less sentient and more appropriate alternatives. In many eases, animals are selected or models are justified for use in experiments because of their degree of evolutionary relatedness to humans. Non-human primates are routinely utilized for no better reason than that monkeys, apes, and humans are all members of the same taxonomic group. However, the questions asked in such projects generally involve functional rather than evolutionary comparisons and concerns. For example, years ago baboons were used in car and plane crash studies because they are primates-ignoring the simple fact that their bodies have little in common with human bodies. Humans and baboons have different spinal configurations, different suspension of internal organs, and other anatomically dissimilar traits relevant to the responses of a quadrapedal body to impact forces designed for bipedal humans.

  The distinction between functional and evolutionary similarities can he used to invalidate most of the research currently done with non-human pri­mates and, to a lesser extent, projects using other species of laboratory animals.

Because of the large amount of  money allocated to study specific diseases, along with the public hysteria prompted by the media and biomedical research industry. investigators may attempt to make their individual research programs relevant’ to the currently popular human affliction. For several decades the motivation for such attributions came from the federal government’s war on cancer. It is unclear how many billions of tax dollars and millions of animal lives were wasted on useless or entirely unrelated cancer research using laboratory animals. More certain, however, is that the war was a well-documented tactical and strategic failure but a financial boon to universities and individual researchers.

Currently, the cancer crisis has been supplanted by an equally questionable, animal-based war on AIdS as the best excuse for otherwise marginally relevant research projects. Consideration of disease focused animal experimentation is often defended by reference to historical trends in human mortality statistics. In fact, critical academic studies have documented that the significant declines in mortality for the past 125 years have almost nothing to do with animal-based biomedical research specifically or medical research in general. There is some evidence that animal experiments have contributed to improvements in human morbidity (illness) hut not mortality.

One of the most persistent myths of the pro-animal research lobby concerns the development of the polio vaccine. Although routinely ascribing this discovery entirely to traditional animal research methods, especially non-human primates, they conveniently fail to mention that the key event which led directly to the vaccine and a Nobel Prize was the development of an alternative method for growing the polio virus in human cell culture not the deaths of thousands of monkeys. The latter were used at the time to produce and test the vaccines, but such usage was more a reflection of inappropriate political decisions and the primitive state of biomedical research in the t95os, rather than of any biological necessity. If begun today, the search for the polio virus and preparation of safe vaccines would he accomplished without killing apes or monkeys. More appropriate alternatives now exist.

The over emphasis on admittedly inappropriate animal models has more to do with scientific traditions and the biases discussed above. Historically, there have not been two systems— in vjvo and in vitro-with the former shown to be superior. Accidents of history and technique development delayed improvements and adoption

Accidents of history and technique development delayed improvements and adoption of alternatives to traditional uses of laboratory animals.

of alternatives to traditional uses of laboratory animals. Today, however, there is no reason for the Red Queen to stay in the same place. There is a better perspective—the alternatives approach to identifying, characterizing, and solving animal and human health problems. 

AAVS