The strategy for defending the use of animals in research appears to involve four positions.
1. Animals can predict human response to drugs and disease. This is proven by the use of animals to find receptors and other targets for drug development.
2. Animal models must be used in basic research, even though they are not predictive for human response. The commonalities that exist between humans and animals have resulted in discoveries that have eventually advanced medical care and this justifies animal use.
3. Regardless of your opinion on animal use, the numbers are decreasing because everyone loves animals and the scientists that use them are really great people (and here).
4. There are laws that protect the animals and everyone respects these laws and the animals.
Not every defender must, or even should, use all four at the same time, as they are actually contradictory to one another. But as long as everyone divides the burden and defends the enterprise in a way that is consistent with their self-interest, the status quo will prevail. Consider the following.
In his blog titled A Proposal for the Labeling of Medicines, at the vivisection activist site Speaking of Research, Dario Ringach discusses polls that report that approximately 52% of Americans state that they support animal-based research but that approximately 85% said they would approve of killing a pig to save their life in the form of replacing their malfunctioning heart valve with one from the pig. He notes a discrepancy between these numbers and opines why this is the case. Ringach: “One likely possibility is that they fail to see the direct link between research and the therapies and medicines that it produces. They fail to see that the medicine that will save their lives next time they visit the emergency room will be, in all likelihood, the result of animal research. They may wrongly perceive basic and translational research as two being completely different things. The contribution of basic knowledge to human health may be lost in translation.”
Ringach suggest that medicines be labeled as being derived from animal-based research. I do not claim to read the minds of the American public surveyed in these polls but I can point out some flaws in Dr Ringach’s conclusions.
When Ringach discusses medication development he is referring to the discovery of receptors and other targets in animals that the drugs are then designed around in order to affect the human disease in question. This is in fact how many of the medications in development came to be there. If this is all one knows about medication development, this would be a prima fascia case for animal-based research. So what is the problem?
It doesn’t work.
Consider the following. Sharp and Langer 2011: “The next challenge for biomedical research will be to solve problems of highly complex and integrated biological systems within the human body. Predictive models of these systems in either normal or disease states are beyond the capability of current knowledge and technology.”(Sharp and Langer 2011)
Giri and Bader 2011: “only one drug out of ~5000-10 000 drug compounds reaches the market after preclinical testing (Hughes et al. 2011).” (Giri and Bader 2011) Preclinical testing includes the animal-based research Dr Ringach is referring to.
Caponigro and Sellers of the Novartis Institutes For BioMedical Research, Oncology Research and Oncology Translational Medicine wrote in 2011: “Despite an improved understanding of the biology of cancer [including the targets Dr Ringach is referring to], and an unprecedented volume of new molecules in clinical trials, the number of highly efficacious drugs approved by the regulatory authorities remains disappointingly low. The significant attrition rate of drugs entering clinical trials comes at a high price. This price is paid primarily by the underserved patient and secondarily by the pharmaceutical and biotechnology community, which invests enormous resources perfecting a molecule only to watch it fail in humans . . .” (Caponigro and Sellers 2011)
Robert Weinberg, of Massachusetts Institute of Technology, was quoted by Leaf in Fortune magazine as saying: “And it’s been well known for more than a decade, maybe two decades, that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings—actual human tumors inside patients—will respond . . . preclinical models of human cancer, in large part, stink . . . hundreds of millions of dollars are being wasted every year by drug companies using these [animal] models.” (Leaf 2004)
Alan Oliff, former executive director for cancer research at Merck Research Laboratories in West Point, Pennsylvania stated in 1997: “The fundamental problem in drug discovery for cancer is that the model systems [animals] are not predictive at all.” (Gura 1997)
The so-called xenograft mice, mice who have cancer from human tumors, have not worked out for predicting the human effects of anti-cancer drugs. Edward Sausville, associate director of the division of cancer treatment and diagnosis for the developmental therapeutics program at the NCI 1997: “We had basically discovered compounds that were good mouse drugs rather then good human drugs.” (Gura 1997)
Littman and Williams of Pfizer writing about using humans as models for other humans in Nature Reviews Drug Discovery 2005: “For the large number of compounds with unprecedented mechanisms of action entering Phase II there are two reasons for failure due to lack of efficacy. These are inadequate pharmacology (not rigorously testing the drug target) and the lack of predictability of animal models, particularly in some therapeutic areas such as oncology and the neurosciences . . .” (Littman and Williams 2005)
John Hodgson, articles editor, in the journal Bio/Technology 1992, on the use of animal tissues to identify new medicines: “One fundamental deficiency of animal tissues is that they contain animal receptors - a boon in the development of drugs for rats, cats, and dogs but of dubious value in human healthcare.” (Hodgson 1992)
If I were going to defend the use of animals in biomedical research, I would not use target identification as an example of success. One success out of 5-10,000 is nothing to brag about. In my opinion, random chance would give better results. Moreover, Dr Ringach should inform NIH and Director Frances Collins that there is no difference between basic and translational research since NIH just opened a new branch dedicated to translational research. (For more on this, I anticipated Dr Ringach’s comments, see here.)
Moreover, the use of heart valves from pigs is not an example of animal-based research but rather an example of using animals for spare parts. As I have pointed out numerous times, this use of animals is scientifically viable in contrast to using animals to predict human response to drugs and disease. This is classic bait and switch, also known as the fallacy of equivocation, on Dr Ringach’s part. Fallacies are the stock-in-trade of those without facts.
Basic science research in general has about the same success rate we find in drug development. According to Crowley, only around 0.004% of basic research publications resulted in a new category of drugs.(Crowley 2003) No wonder vivisection activists want to conflate translation with basic research. When animal models are conclusively shown not to predict human response, vivisection activists cannot fall back on the “animal-based basic research is essential” argument either. (For more on basic research, see Is the use of sentient animals in basic research justifiable?)
James V. Parker and P. Michael Conn of the Oregon Health and Science University echoed Ringach’s position in an article for The Scientist, stating: “the public doesn’t understand the connection between animal research and personal health.” Parker and Conn call for physicians to come to the aid of animal experimenters in defending the value of vivisection for human health and the development of medications. In reality, that is the one thing society is very clear on. Giles, writing in Nature: “In the contentious world of animal research, one question surfaces time and again: how useful are animal experiments as a way to prepare for trials of medical treatments in humans? The issue is crucial, as public opinion is behind animal research only if it helps develop better drugs. Consequently, scientists defending animal experiments insist they are essential for safe clinical trials, whereas animal-rights activists vehemently maintain that they are useless.”(Giles 2006) Society does see the difference between replacing a heart valve with one from a pig and the extremely poor track record of basic research using animals and animal-based research for drug development. Furthermore, in terms of getting support from physicians, I have criticized the MD community (along with other communities of scientists) because even though they privately readily acknowledge that animal-based research is a waste of resources, they will not voice those opinions publicly. If the physician community as a whole ever speaks out, it will not be to the liking of Parker and Conn. (Vested interest groups within the physician community can be found that support animal-based research.)
Andrew Rowan of the HSUS wrote a response to the Parker Conn piece in which he stated: “Since the mid-seventies, the use of animals has fallen by around 50 percent.” I have addressed this in previous blogs, but suffice it to say that the numbers Dr Rowan is using are estimates based on data supplied by the animal experimentation industry. No bias there. Unbiased estimates show an exponential increase. (Today, I learned that documented animal use in Germany has increased from 2005 to 2009.)
Finally, we have the laws and or regulations of the United States of America. The NIH issued a moratorium on breeding chimpanzees around 1995 only to find in 2010 that it had been ignored. An editorial in Nature stated: “Until officials are fully open with the public and demonstrate convincingly that the research centres they help to fund are both competent and compliant with the rules — and that, when they are not, the proper sanctions will ensue — US chimpanzee research risks losing public support entirely, and with good reason.”(Editorial 2011) Every time a person has gone undercover to work in a research lab, that I know of, numerous violations of the Animal Welfare Act have been documented as well as gross misconduct in terms of animal abuse. Every time. It is difficult to reconcile that with statements by people like Andrew Rowan of the HSUS.
Taken individually or collectively the arguments made by vivisection activists do not stand up to scrutiny. If the use of animals in research was about science, this would matter. But its not about science, its about money so don’t expect accountability any time soon.
Caponigro, G., and W. R. Sellers. 2011. Advances in the preclinical testing of cancer therapeutic hypotheses. Nat Rev Drug Discov 10 (3):179-87.
Crowley, W. F., Jr. 2003. Translation of basic research into useful treatments: how often does it occur? Am J Med 114 (6):503-5.
Editorial. 2011. Breeding contempt. Nature 479 (7374):445-445.
Giles, J. 2006. Animal experiments under fire for poor design. Nature 444 (7122):981.
Giri, Shibashish, and Augustinus Bader. 2011. Foundation review: Improved preclinical safety assessment using micro-BAL devices: the potential impact on human discovery and drug attrition. Drug Discovery Today 16 (9/10):382-397.
Gura, T. 1997. Cancer Models: Systems for identifying new drugs are often faulty. Science 278 (5340):1041-2.
Hodgson, J. 1992. Receptor screening and the search for new pharmaceuticals. Biotechnology (N Y) 10 (9):973-80.
Hughes, J. P., S. Rees, S. B. Kalindjian, and K. L. Philpott. 2011. Principles of early drug discovery. British Journal of Pharmacology 162 (6):1239-1249.
Leaf, C. 2004. Why we are losing the war on cancer. Fortune (March 9):77-92.
Littman, B. H., and S. A. Williams. 2005. The ultimate model organism: progress in experimental medicine. Nat Rev Drug Discov 4 (8):631-8.
Sharp, Phillip A., and Robert Langer. 2011. Promoting Convergence in Biomedical Science. Science 333 (6042):527.