In Dr Ringach’s response to my essay on his issues with my position on using animals in research, he continues to maintain that Dr Shanks and I took quotes out of context. So be it. I have refuted this and offered quotes from our book Animal Models in Light of Evolution where we proactively addressed this. We do not and did not quote anyone out of context. If Dr Ringach wishes to perseverate such a claim there is nothing I can do but suggest that anyone who wishes to pursue the subject further actually read what we wrote and make your own decision. While I have no fear what the scientific community as a whole will have to say about this I also have no doubt that people who use animals in research will continue to make the out of context claim.
It is unfortunate that Dr Ringach compares us to antiscience zealots like creationists. By ignoring the science that undergirds our position and instead bringing up what can charitably be described as a red herring (although his red herring is not valid) Dr Ringach debases science and the long scientific tradition of serious civil discourse on contentious scientific issues. Tempers will flare in discussions about science as well as discussions about religion and politics but scientists should be above name-calling and focus on the facts. Such misleading and inaccurate allegations inhibit mutual understanding and diminish society’s value of science in general and scientific discussion.
As to Dr Ringach’s suggestion for a conversation about the use of animals in anesthesia research, I must point out that I cannot comment on every subtopic of animals in research. There is simply not enough time. One reason we wrote Animal Models in Light of Evolutionwas so we could address the overarching theory pertaining to why animal models are not predictive for human response to drugs and disease. By doing this we can dispense with addressing why animals models are not predictive for subtopic A, B, C and so forth. An imperfect analogy would be the fact that an understanding of the Second Law of Thermodynamics precludes a perpetual motion machine. Instead of analyzing every patent for such a machine, the US Patent Office can merely refer the applicant to the Second Law. (In fact, it is my understanding the Patent Office does not even consider such applications nor should they.) We have never said that using animals as heuristic devices is scientifically untenable. I assume that they can be used in such a fashion for the study of anesthesia as well as in other areas.
One final note on why I am calling for a debate at the UCLA campus. When Drs Ringach and Jentsch wanted to host a panel discussion on the issue of animals in research, I agreed to participate providing the event would be followed by a debate on the prediction issue. After that debate, if Drs Ringach and Jentsch desired, we could debate any other aspect of using animals in science. No topic would be off limits. That was the agreement. Dr Ringach, at least, has reneged on this agreement.
Predict has a very specific meaning in science and can be measured by simple mathematics in the form of sensitivity, specificity, positive predictive value, and negative predictive value. Scientists who use animal models in research do claim they use them for predicting human response. For example, Gad:
Biomedical sciences’ use of animals as models to help understand and predict responses in humans, in toxicology and pharmacology in particular, remains both the major tool for biomedical advances and a source of significant controversy . . . At the same time, although there are elements of poor practice that are real, by and large animals have worked exceptionally well as predictive models for humans-when properly used. . . Whether serving as a source of isolated organelles, cells or tissues, a disease model, or as a prediction for drug or other xenobiotic action or transformation in man, experiments in animals have provided the necessary building blocks that have permitted the explosive growth of medical and biological knowledge in the later half of the 20th century and into the 21st century…. Animals have been used as models for centuries to predict what chemicals and environmental factors would do to humans. . . . The use of animals as predictors of potential ill effects has grown since that time [the year 1792]. Current testing procedures (or even those at the time in the United States, where the drug [thalidomide] was never approved for human use) would have identified the hazard and prevented this tragedy. (Gad 2007) (Emphasis added.)
In a similar vein Hau notes:
A third important group of animal models is employed as predictive models. These models are used with the aim of discovering and quantifying the impact of a treatment, whether this is to cure a disease or to assess toxicity of a chemical compound. (Hau 2003) (Emphasis added.)
Fomchenko and Holland 2006: “GEMs [genetically engineered mice] closely recapitulate the human disease and are used to predict human response to a therapy, treatment or radiation schedule” (Fomchenko and Holland 2006) (Emphasis added). The implication that animal models can be used to predict human response also shows up in basic neuroscience researcher’s applications for taxpayer money. Grant Number: 1R01NS050156-01A2:
Project Title: Focal Dopamine Indicated in Dyskinesias in MPTP Monkeys
Abstract: The broad aim of this proposal is to test the hypothesis that L-dopa-induced dyskinesias (LID) in Parkinson’s disease (PD) arise at least in part from non-uniform dopaminergic denervation of the striatum, whereby islands of dopaminergic activity (hotspots) are created within the most severely affected part of the striatum, the post-commissural putamen . . . This research program is important from three perspectives. First, it promises to establish an in vivo model of LID in which neural correlates of LID can be investigated in a controlled setting. This work will provide insight on the mechanisms behind L-dopa induced dyskinesias and will provide a basis for using gene therapy approaches to treat patients with Parkinson’s disease. (Emphasis added.)
All of this is covered in Animal Models in Light of Evolution.
Predict does not mean getting the right answer occasionally or suggesting further topics for investigation. These concepts are in the arena of basic research. The question as to whether animal models are predictive for human disease and drug response must be resolved prior to any other discussion of animals in science or basic research as, if animal models are not predictive, it will impact on the rest of the debates. If the question is not resolved, then prediction of animal models will simply continue to be cited by the animal experimenters as a given. I am happy to debate Dr Ringach on any aspect of using animals in science provided the prediction issue is settled first. If Dr Ringach believes animals are predictive, then we have a disagreement that needs to be aired. If he does not, then he can merely say so and we can move on to whatever debate he wants. I believe a debate on the use of animals in neuroscience research would be very beneficial for society and look forward to participating in it.
Fomchenko, E. I., and E. C. Holland. 2006. Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 12 (18):5288-97.
Gad, SC. 2007. Preface. In Animal Models in Toxicology, edited by S. Gad: CRC Press.
Hau, Jann. 2003. Animal Models. In Handbook of Laboratory Animal Science. Second Edition. Animal Models, edited by J. Hau and G. K. van Hoosier Jr: CRC Press.