We thank Dr Wolpert for taking his time and applying his considerable intellect to review our book Animal Models in Light of Evolution. We are honored that Dr Wolpert reviewed our book.
We wrote the book in order to prove one point: that animals cannot predict human response to drugs and disease. We state:
"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." p24
Therefore we are very happy that Dr Wolpert thinks the book:
". . . 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."
That is exactly what the book was about.
We actually agree, in part, with Dr Wolpert when he points out that we ignored similarities among species and breakthroughs that involved animals. We acknowledged many times in the book that animals and humans have traits in common and that past breakthroughs used animals. For example:
"We are about to begin a detailed analysis of the roles played by animals in biomedical research. This is a good place to make clear, once again, what we are interested in, and what we are not. There can be no doubt whatsoever that if you wish to make discoveries about rats and mice you will be forced of methodological necessity to perform careful scientific studies of R. rattus and M. musculus respectively. In fact, in writing this book, we are the beneficiaries of the results of careful scientific studies of animals. There is no doubt that careful biological studies of rats and mice can help clarify the general contours of mammalian biology. Such studies can also play a valuable heuristic role by prompting new ways of thinking about human biological problems of interest. The issue we are concerned with is this: notwithstanding these cautions, are animal models predictive of human outcomes in, say, toxicology, drug discovery, and the study of the causes and cures of human diseases? . . . This book is not intended to be a criticism of the use of animals in the context of basic biological research. There can be no doubt that careful studies of animals have prompted important hypotheses about basic biological principles, and there can be no doubt that studies of animals have contributed greatly to our scientific understanding of life, and there is little doubt that these studies will continue to illuminate these matters in the future (items (7) and (9) above)." p28-30
And:
"We remind the reader once again that the target of our criticism of animal-based research is restricted to the practice of predictive modeling. We do not dispute that there are legitimate roles for animal test subjects in other kinds of experimental investigation—for example basic biological research aimed at increasing the sum total of human knowledge. Animal experiments in the context of basic research may enrich our knowledge of specific phenomena in mice, and, if painting is permitted with a broad enough brush, they may help delineate some of the important contours of mammalian biology, from which lessons about the Eukaryotes and even life itself might be forthcoming". p351
However, the issue of prediction, which we go to great lengths to define for medical science, does not hinge on past discoveries or phylogenetic similarities. Our purpose in ignoring examples of trans-species similarities or past discoveries was not to slight animal use per se, but rather to avoid what would have been a protracted debate on a topic that was of peripheral interest. (For example, using heart-valve replacement, coronary artery bypass, and open-heart surgery as examples of animal model success stories is very contentious. Animal models both misled and were heuristic in those cases. To really analyze which was more important is work for another book.) By focusing on one and only one facet of using animals in science we were able to go into the depth demanded by such a contentious topic.
Regardless, even the examples that Dr Wolpert cites—Harvey’s use of animals to determine the circulation of blood, Koch and germs, and the work of Pasteur—support our point in that these example occurred at a time when science knew very little and the easily observed similarities among species outweighed the differences. Animal Models in Light of Evolution discusses the use of animals as predictive models for today’s problems of complex diseases like cancer and AIDS and responses to drugs where interspecies differences, and even intraspecies differences, have proven important.
We do think Dr Wolpert misses the mark when he states real progress toward curing Huntington’s has come from studying mice. The study of mice may indeed, when viewed through the lens of history, be seen to play an important role in the eventual prevention and or cure of this disease, but claiming such at this point relies on the assumption that animal models are predictive.
We thank the editors of Philosophy, Ethics, and Humanities in Medicine for publishing Dr Wolpert’s review and again thank Dr Wolpert for his interest.
Appreciation for review
2 September 2010
We thank Dr Wolpert for taking his time and applying his considerable intellect to review our book Animal Models in Light of Evolution. We are honored that Dr Wolpert reviewed our book.
We wrote the book in order to prove one point: that animals cannot predict human response to drugs and disease. We state:
"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." p24
Therefore we are very happy that Dr Wolpert thinks the book:
". . . 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."
That is exactly what the book was about.
We actually agree, in part, with Dr Wolpert when he points out that we ignored similarities among species and breakthroughs that involved animals. We acknowledged many times in the book that animals and humans have traits in common and that past breakthroughs used animals. For example:
"We are about to begin a detailed analysis of the roles played by animals in biomedical research. This is a good place to make clear, once again, what we are interested in, and what we are not. There can be no doubt whatsoever that if you wish to make discoveries about rats and mice you will be forced of methodological necessity to perform careful scientific studies of R. rattus and M. musculus respectively. In fact, in writing this book, we are the beneficiaries of the results of careful scientific studies of animals. There is no doubt that careful biological studies of rats and mice can help clarify the general contours of mammalian biology. Such studies can also play a valuable heuristic role by prompting new ways of thinking about human biological problems of interest. The issue we are concerned with is this: notwithstanding these cautions, are animal models predictive of human outcomes in, say, toxicology, drug discovery, and the study of the causes and cures of human diseases? . . . This book is not intended to be a criticism of the use of animals in the context of basic biological research. There can be no doubt that careful studies of animals have prompted important hypotheses about basic biological principles, and there can be no doubt that studies of animals have contributed greatly to our scientific understanding of life, and there is little doubt that these studies will continue to illuminate these matters in the future (items (7) and (9) above)." p28-30
And:
"We remind the reader once again that the target of our criticism of animal-based research is restricted to the practice of predictive modeling. We do not dispute that there are legitimate roles for animal test subjects in other kinds of experimental investigation—for example basic biological research aimed at increasing the sum total of human knowledge. Animal experiments in the context of basic research may enrich our knowledge of specific phenomena in mice, and, if painting is permitted with a broad enough brush, they may help delineate some of the important contours of mammalian biology, from which lessons about the Eukaryotes and even life itself might be forthcoming". p351
However, the issue of prediction, which we go to great lengths to define for medical science, does not hinge on past discoveries or phylogenetic similarities. Our purpose in ignoring examples of trans-species similarities or past discoveries was not to slight animal use per se, but rather to avoid what would have been a protracted debate on a topic that was of peripheral interest. (For example, using heart-valve replacement, coronary artery bypass, and open-heart surgery as examples of animal model success stories is very contentious. Animal models both misled and were heuristic in those cases. To really analyze which was more important is work for another book.) By focusing on one and only one facet of using animals in science we were able to go into the depth demanded by such a contentious topic.
Regardless, even the examples that Dr Wolpert cites—Harvey’s use of animals to determine the circulation of blood, Koch and germs, and the work of Pasteur—support our point in that these example occurred at a time when science knew very little and the easily observed similarities among species outweighed the differences. Animal Models in Light of Evolution discusses the use of animals as predictive models for today’s problems of complex diseases like cancer and AIDS and responses to drugs where interspecies differences, and even intraspecies differences, have proven important.
We do think Dr Wolpert misses the mark when he states real progress toward curing Huntington’s has come from studying mice. The study of mice may indeed, when viewed through the lens of history, be seen to play an important role in the eventual prevention and or cure of this disease, but claiming such at this point relies on the assumption that animal models are predictive.
We thank the editors of Philosophy, Ethics, and Humanities in Medicine for publishing Dr Wolpert’s review and again thank Dr Wolpert for his interest.
Ray Greek
Niall Shanks
Competing interests
We are the authors of the reviewed book