Continued from part I.
Magee also points out, correctly, that almost every study we quote also states that animal models are invaluable for medical science to continue. We have addressed this many times including in Animal Models in Light of Evolution (p27):
The FACTS of species differences relevant to the prediction issue are not in question. What is at issue are the INTERPRETATIONS authors place on the facts they refer to. We are justified in citing facts (and quoting researchers who do so) while rejecting interpretations. We cite many examples of the same phenomenon (species difference) to establish that it is a more or less agreed fact. Our point is not to get involved in an endless ding-dong about examples but to suggest that there are other well-established ways to deal with what we see (i.e. evolutionary biology). It matters not to us that those referring to the facts of species differences are also ardent advocates of animal experimentation. What matters are the facts, along with consideration of alternative hypotheses about their significance. We will offer some alternative hypotheses about the significance of the facts we uncover. Science, after all, is as much driven by disputes about the meaning and significance of facts as it is about the facts themselves. We have nothing to apologize for in this regard. (Capitals in original but bold added.)
Since most of the people we quote or cite are themselves animal modelers, it would be a shock if they did not say something positive about their research method. They are entitled to this, but we are also allowed to interpret the very impressive data they present as revealing that animal models have very little predictive value at higher levels of organization such as where drugs and diseases act and to explain why we think our interpretation of the data is correct. Statements against interest, on the other hand, are impressive on their own merit and such statements abound from animal modelers.
Magee also seems to have only minimal understanding of complexity science: “Arguing that animal models are not predictive because life is complex, when there hasn’t been a single death during a phase 1 clinical trial in the UK in over 30 years (and only one serious incident, due to human error), is a bit like arguing that airplanes can’t fly whilst being seated on an airplane at 30,000 feet.” Three points: 1. Data on who has died in Phase I trials is proprietary and any death-based lawsuits are probably settled out of court. Arguments from ignorance (we do not know how many people die in Phase I clinical trials) are not valid. 2. It does appear that in India, where many Phase I trials are done, they have a reasonably high death rate from clinical trials in general. For more on the problems of using animals to determine dose for first in man see . 3. Magee is clearly stating that animal studies are used to confirm safety for first-in-man Phase I clinical trials. This means Magee thinks they have predictive value and are used to predict human response, which is somewhat contrary to earlier statements by Magee. But, many vivisection activists have stated this is true for first in man trials. However, many others claim that animal studies are performed so that all people receiving the drug will be safer. It takes different data to support or negate these claims and vivisection activists rarely provide data. Magee’s reference to first-in-man deaths in the UK being an example of where no data is provided.
Magee goes on, and I have ignored many previous claims, but my main issue with the essay is the same issue I have with almost every critique of the work Shanks and I have published. Our main message has always been some version of the following. From Animal Models in Light of Evolution (p24):
The purpose of this book is to address the ability, or lack thereof, of animals to predict human response and to see what other roles they may have in research and testing. We will argue that claims concerning the great utility of animals as predictive models of human biomedical phenomena are unsupported by evidence and are compromised by both methodological issues and issues arising from basic biological theory.
From Animal Models in Light of Evolution (p358):
Our position can be summarized as follows: Living complex systems belonging to different species, largely as a result of the operation of evolutionary mechanisms over long periods of time, 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 organization (humans and rats may be intact systems, but may be differently intact); (9) differences in environmental exposures; and last but not least; (10) differences with respect to evolutionary histories. These are some of the important reasons why members of one species often respond differently to drugs and toxins, and experience different diseases. Immense empirical evidence supports this position.
Many other such quotes could be produced from all of our writings. I have recently formulated this message into Trans-Specia Modeling Theory (TSMT):
While trans-species extrapolation is possible when perturbations concern lower levels of organization or when studying morphology and function on the gross level, one evolved, complex system will not be of predictive value for another when the perturbation affects higher levels of organization.
All of the above are concise explanations of a very complicated, trans-disciplinary position. I am always amused when I see critiques of the position from people that obviously do not know what some of the words and concepts even mean. If people want to criticize our position, they must first be familiar with it and only one critique  has revealed even minimal familiarity. For my response to that criticism see . (I am hoping that author will continue our dialogue.)
There are some that have read and understood the books and articles. Compare their interpretation with what I stated above and with what Magee and others have claimed was the position of the book. Rachel A. Ankeny of the Department of History & Politics at the University of Adelaide, Adelaide, Australia offers a reasonable review of Animal Models in Light of Evolution:
Nonetheless, the authors do an admirable job of situating their discussions against the backdrop of relevant theories and information from evolution theory and systems biology, while at the same distancing their arguments from claims about animal ethics or rights, the typical domain where debates about the validity of animal models have previously occurred. Perhaps most importantly, they do not attempt to take their conclusions too far, and grant that nonhuman animals can be used for some forms of basic biological research where prediction for human health is not the main goal.  (Emphasis added.)
Lewis Wolpert also appears to understand the main point of Animal Models in Light of Evolution when he reviews the book:
Animal Models in the Light of Evolution provides persuasive evidence that animal models should be used with great caution when applying the results to human diseases. Mice and other model animals are both similar and different, in their biology, to humans. It is rather technical and not easy reading. [That’s the truth!] . . . Arguments from evolution are used to show the fundamental differences between, for example, rats and humans, as the organisms are too complex for information about one to be applied to the other. The authors discuss this complexity in terms of dynamical systems theory and its mathematical basis and question the possible similarity of such systems in different mammals. Quite small changes can have significant effects. They use such views to raise doubt on just how much genes contribute to an organism's form and function, but their arguments are themselves complex and hard to follow, and there is no persuasive evidence. It is no mystery that mice can differ significantly from humans in their response to drugs.
I could take exception to some of the comments in the above two reviews but at least the two reviewers understood the basis for our position. Comments like the above from Magee miss the big picture either from ignorance or malice.
Wolpert is right—our position is technical, requires trans-disciplinary education, and is not easy. Moreover, it is unpopular as the hierarchy of academia will change dramatically as will salaries. I have presented posters at the largest conferences in evolutionary biology and complex systems. The attendees walk by, read the poster, say they agree with me and ask why I am at their meeting as everyone already knows all this. After all, they say, no one uses animals as surrogate humans in biomedical research anyone. They are only used for basic research. I show them a few grant applications that claim the research project will directly cure humans and they are aghast. So, I ask them to sign a petition that states the following scientists agree with TSMT. They refuse and then they all say the same thing. “No. I agree with you but I would lose my job. My university will not allow us to voice opposition to something that brings in money to the university.” Needless to say, I do not have any of that on tape. But the experts in the two fields on which our position is based agree with us while the basic researchers that use animals use fallacy after fallacy along with obfuscation to try and confuse society and justify their research. They never address our position or the issues that arise out of it. Suffice it to say Magee is not an exception to that rule.
I am happy to correct mistakes made in any of our books or articles and actually appreciate them being pointed out. But I will in the future resist responding to people who are the equivalent of young earth creationists in that they simply do not have enough appreciation of the science to understand why their questions and comments are not even wrong. In the future, if someone wants to engage me in a discussion of TSMT please demonstrate that you at least understand what we are saying by explaining it in your first or second paragraph. Only then will I comment on your issues.
Essays like Magee’s and Gorski’s recent post are why I have also changed my criteria for debates. The recent Bill Nye debate notwithstanding, most science debates would benefit from the rules I list here. I would also suggest the same concepts be employed in debates in the scientific literature. That being said, I welcome the opportunity to engage in a fair and proper debate either in the scientific literature or in a public forum. Once again, I am not holding my breath waiting for a response.
9. Greek R, Hansen LA: Questions regarding the predictive value of one evolved complex adaptive system for a second: exemplified by the SOD1 mouse Progress in Biophysics and Molecular Biology 2013:http://dx.doi.org/10.1016/j.pbiomolbio.2013.1006.1002. http://www.sciencedirect.com/science/article/pii/S0079610713000539
10. Shanks N, Greek R: Animal Models in Light of Evolution. Boca Raton: Brown Walker; 2009.
11. Greek R, Rice MJ: Animal models and conserved processes. Theoretical Biology and Medical Modelling 2012, 9(40). http://www.tbiomed.com/content/9/1/40/abstract
58. Shelley C: Why test animals to treat humans? On the validity of animal models. Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 2010, 41(3):292-299. http://www.sciencedirect.com/science/article/B6VHP-50NH66T-3/2/adf77c24c844a88e0c8b93547272a7b9
59. Greek R, Shanks N: Complex systems, evolution, and animal models. Stud Hist Philos Biol Biomed Sci 2011, 42(4):542-544. http://www.ncbi.nlm.nih.gov/pubmed/22035727
60. Ankeny RA: Book Review: Animal Models in Light of Evolution. Q Rev Biol 2011, 86(September):223-224.
61. Wolpert, Lewis. 2010. Review of "Animal Models in the Light of Evolution" by Niall Shanks, Ph.D., and C. Ray Greek, M.D.Philosophy, Ethics, and Humanities in Medicine. doi: 10.1186/1747-5341-5-12. http://www.peh-med.com/content/5/1/12