Animal Rights

Animal Models and Conserved Processes

| by Dr Ray Greek

If scientists want to argue for the value of using animals in research, aside from their value as heuristic devices in basic research, they should argue based on conserved processes. Although this argument would eventually fail, it is far superior to the ad hominems, cherry picked data, other fallacies, and vituperative rhetoric they usually use to make their case.

Marc W. Kirschner of Harvard Medical School and John C. Gerhart of the University of California, Berkeley, write about conserved processes in their book The Plausibility of Life: Resolving Darwin's Dilemma (Yale University Press, 2005). I refer the interested reader to The Plausibility of Life for more details.

What brought this topic to mind was an article in Science: Plant and Animal Sensors of Conserved Microbial Signatures. The first two paragraphs of the article:

The mechanisms of plant and animal defense against microbes have historically been presumed to be separate and distinct (fig. S1). Beginning around the 1870s, studies of animal responses to infection revealed the existence of both “natural” or innate immunity, which involved the cells and molecules mediating host inflammatory responses, and adaptive immunity, which permitted the generation of cellular receptors with immense diversity and exquisite specificity for foreign macromolecules of almost any kind. Lacking phagocytes, lymphocytes, antibodies, and many other parts of the animal armamentarium, it seemed that the plant response to disease must use a fundamentally different strategy.

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However, discoveries over the past 15 years demonstrate that the mechanisms that allow plants and animals to resist infection show impressive structural and strategic similarity (Fig. 1). Remarkably, the elucidation of these mechanisms followed a common approach involving a concerted attack on the same basic questions: What molecules are recognized by the host as signatures of infection? What receptors mediate recognition? These questions were ultimately answered by classical genetic studies.

Animals and plants both have protein molecules that reside on the cell surface called receptors. Some of these receptors recognize foreign proteins and tell the animal or plant to defend itself against this invasion. This similarity is seen in plants and animals.

But the authors also point out that there are differences between species:

. . . Drosophila's immune system depends on only one immunologically active receptor, known as the Toll receptor, to sense invasion by fungi and gram-positive bacteria. In contrast, Arabidopsis has dozens of sensors to protect against microbial infections and rice has hundreds.

Studying life forms will enable one to learn more about life. This is a tautology. That basic research will lead to more knowledge is another tautology if by basic one means that by asking interesting questions and doing experiments, knowledge will be advanced. But conserved processes and basic research do not mean animal models can predict human response to drugs and disease, even in infectious diseases. For example:

Vaccines that successfully prevented infection of SIV in monkeys did not prevent infection with HIV in humans.

“Efforts to establish HIV1 infection in primates have proven largely unsuccessful. Early studies inoculating chimpanzees with plasma from HIV1-infected patients did not result in measurable pathogenic changes or AIDS induction.” (Stump and VandeWoude 2007)

Johnston 2000:

Monkeys: The viruses HIV-1, HIV-2, and the main SIV viruses used, SIVagm and SIVmac are very different. HIV-1 shares only 40% homology with the other viruses. HIV-2 and SIV share only 75% homology. HIV differs from SIV at the very important hypervariable region. SIV enters the cells of rhesus monkeys by binding to the CCR5 receptor without binding to the CD4 receptor. In humans, HIV must bind to both CCR5 and CD4 receptors. A single amino acid difference in the CCR5 terminus was responsible for the difference in binding. Another difference is that SIV isolates use the CCR5 coreceptor for virus uptake into cells. In 40–50% of HIV-infected humans, HIV that uses CCR5 predominates early and throughout the asymptomatic phase of a typical HIV infection, but a shift of tropism to CXCR4 is observed as these humans progress to AIDS. This shift has not been reported in SIV-infected macaques. (Johnston 2000)

Anthrax is another example. Richard Knox, NPR correspondent on Talk of the Nation, October 31, 2001:

And for some weeks, the official statements made it sound as though there was a threshold; it required something like 8,000 or 10,000 spores to be inhaled and these had to be, you know, very tiny spores, not clumped together, in order to have inhalation anthrax as a result.  But I think that was--it was always misleading and never were able to explain except, you know, the past couple of days has begun to be.  It was based on monkey studies.  It meant that of a group of monkeys exposed to 8,000 to 10,000 spores per monkey, that half of them would die as a result.  It really was totally unknown what proportion of either animals or humans exposed to a smaller number of spores would get sick and die.

Dr. David Kessler, former director of the FDA stated on the same program, “We don't know how many spores it takes.”

Hepatitis C virus only infects humans and chimpanzees in part because the virus must bind to four different molecules on the surface of liver cells, including CD81 and occludin.

The use of nonhuman primates as predictive models for humans delayed the polio vaccine for decades. Scientists did successfully use nonhuman primates to grow the virus but that is not the same as using them as predictive models.

I recommend Plant and Animal Sensors of Conserved Microbial Signatures for anyone interested in science in general, evolution, or comparative biology. It is a very good article.

Animal models ultimately fail as predictive models for humans, despite the presence of conserved processes, because animals and humans are complex systems. Of course, if you do not understand what a complex system is or if your livelihood depends on selling society on the falsehood that animals can predict drug and disease response in humans, then you will probably ignore that pesky little detail.

 References

Johnston, M. I. 2000. The role of nonhuman primate models in AIDS vaccine development. Mol Med Today 6 (7):267-70.

Stump, D. S., and S. VandeWoude. 2007. Animal models for HIV AIDS: a comparative review. Comp Med 57 (1):33-43.