Americans For Medical Advancement (AFMA) was established in 1999 by Ray Greek, MD and Jean Swingle Greek, DVM, whose goal it was to develop a mainstream, science-based research and educational group dedicated to improving policy and decision-making regarding the use of the animal model in biomedical research.
In evaluating which purposes animal can legitimately be used in science, and which purposes are not scientifically viable, our position is that animals can be used successfully in science for many endeavors, including dissection, basic research, as bioreactors, as heuristic devices, and to provide tissues for human use (such as heart valves from pigs). However, they cannot be used to predict human response to drugs or the pathophysiology of human disease.
When AFMA was formed in 1999, the case against the predictivity of animal models for human drug and disease response were of the empirical or clinical variety. A wide variety of clinical studies, anecdotes and case reports had shown that when compared with how drugs ultimately affected humans, the animals had reacted the same way in few enough cases to have failed to meet the burden of predictivity.
From the perspective of the physician practicing medicine in the real world, this evidence would be sufficient to abandon the use of animals to predict drug and disease response in humans. For the clinician engaged in the world of cancer patients and auto accident victims, human response is the final arbitrator of truth—not what happens in a laboratory with animals. So when they see a drug kill even a small number of patients, that is enough proof for them to stop administering that drug, regardless of how much the drug was studied in the laboratory and what was learned from those studies. They don’t need to know—and are not necessarily even interested in—the pharmacology and physiology of the drug in eight different animal species.
Far from the often messy and chaotic world of clinical medicine, some medical researchers believe, and have stated, that the laboratory (meaning the laboratory where animals are used) is the true sanctuary of medicine, not the clinic or hospital where clinical studies are performed. Indeed, clinical medicine is fraught with variables that cannot be controlled, thus leaving any clinical study or observation open to criticism and second-guessing. In this respect, the researchers are correct in their assertion that laboratory-based research is much more controlled, and thus from their perspective, authentic, than clinical medicine.
Thus, while empirical evidence in the form of clinical observations and studies, case reports and anecdotes, could on its own defeat the claim of predictability by the animal model community, the community that uses animals, as well as some who do not, demands more, for they believe that what one aims for in science is an overarching theory that can predict outcomes without having to perform experiments every time a question is raised. Therefore, they assert that evidence previously put forth has not been scientific enough, for it has failed in their view to adequately answer the “big” question—why?
For medical science, the reason why animals sometimes react as humans but more often do not is being illuminated by our knowledge about genes, gene regulation, gene expression, gene networks, which has come in large part from the results of the Human Genome Project and other similar genome projects. This knowledge allows us to formulate an overarching theory to explain what we have observed empirically for decades.
All animals are examples of robust complex systems (on many levels) and hence have emergent, modular and nonlinear properties. Perturbations in complex system S1 that lead to affect A will not necessarily lead to effect A in complex system S2, regardless of how similar the two systems are or were.
Living complex systems also manifest different responses to the same stimuli due to: 1) differences with respect to genes present; 2) differences with respect to mutations in the same gene (where one species has an ortholog of a gene found in another); 3) differences with respect to proteins and protein activity; 4) differences with respect to gene regulation; 5) differences in gene expression; 6) differences in protein-protein interactions; 7) differences in genetic networks; 8) differences with respect to organismal organizations (humans and rats may be intact systems, but may be differently intact); 9) differences in environmental exposures; and last but no leads (10 differences with respect to evolutionary histories.
These are some of the important reasons why even two nearly identical complex systems (e.g., a chimpanzee and a human or even monozygotic twins) may respond differently to drugs and experience different diseases, and hence why one complex system/species cannot reliably predict responses for a different complex system/species.
Current biomedical research is studying disease and drug response at the level where the differences between complex systems (be they two different species or two different humans) become momentous, hence using animals (e.g., vertebrates) as predictive or causal analogical models (CAMs) for human diseases and drug testing is a scientifically invalid paradigm.
These developments, which have occurred just in the past decade, represent a major leap forward not just for medical science in general, but for presenting the case against using animals (e.g., vertebrates) as predictive models or CAMs for human diseases and drug testing with what is considered within the research community a more scientifically respectable argument.
