Animal Rights

There is Only One Evolution

| by Dr Ray Greek

I have frequently pointed out that pharmaceutical companies acknowledge that animal models are not predictive for human response in terms of efficacy or toxicity. More evidence for this position comes from Robert G. Hunter in an article in Genetic Engineering & Biotechnology News.[1] Hunter: “Having developed over the past 20 years into a global market recently estimated at $5 billion, in vitro and in silico products and services are now about the same size as the in vivo services (contract research organization) industry.” If animal models worked well, there would be no need for industry to look at other options. Pharma does not love bunnies. Pharma loves money.

Matthew Herper addressed the problems in drug development in an article in Forbes.[2] Herper:

There’s one factor that, as much as anything else, determines how many medicines are invented, what diseases they treat, and, to an extent, what price patients must pay for them: the cost of inventing and developing a new drug, a cost driven by the uncomfortable fact than 95% of the experimental medicines that are studied in humans fail to be both effective and safe.

Animal models are relied on for the evaluation of both efficacy and safety.[3-9] Herper continues:

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A new analysis conducted at Forbes puts grim numbers on these costs. A company hoping to get a single drug to market can expect to have spent $350 million before the medicine is available for sale. In part because so many drugs fail, large pharmaceutical companies that are working on dozens of drug projects at once spend $5 billion per new medicine. . . . “This is crazy. For sure it’s not sustainable,” says Susan Desmond-Hellmann, the chancellor at UCSF and former head of development at industry legend Genentech, where she led the testing of cancer drugs like Herceptin and Avastin. “Increasingly, while no one knows quite what to do instead, any businessperson would look at this and say, ‘You can’t make a business off this. This is not a good investment.’ I say that knowing that this has been the engine of wonderful things.”

This, in part, is why disease-specific drugs like Kalydeco, a drug for cystic fibrosis (CF) patients that have a specific genetic mutation, costs $294,000 per patient per year.

The reason animal models fail for drug development is that animals and humans are evolved systems that are differently complex. While morphological similarities exist, very small differences in the genetic make-up between species and between individuals of the same species means the predictive value for extrapolation is nil in the real world. (For more on this see Trans-Species Modeling Theory.) Moreover, if the concept of evolved, complex systems invalidates trans-species extrapolation in drug development, it is going to do the same when trans-species extrapolation involves any perturbation that affects higher levels of organization. So just based on the evidence from drug development we can safely say that disease research on mice, monkeys, or dogs is not going to result in knowledge that has predictive value for human patients. The literature confirms this.[10-21][[22]p19-33, 73-77] [23-25]

Compare the above to this recent statement from Michael E. Goldberg published in the Wisconsin State Journal: “Nearly every medical advance from the last century is a product of responsible animal research, and animal models will continue to be important to medical progress. . . . Activists who claim animal research does not benefit humans are wrong. Animals are essential to medical progress in all fields of human disease.” [26] This illustrates the dichotomy regarding animal models. Dr Goldberg is an animal modeler who does basic research, which he sells as applied research. Not surprisingly, Goldberg thinks animal modeling is great. He does not suffer loss of income or prestige when the knowledge from animal modeling fails to translate to human patients.

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Pharma on the other hand, can actually measure the success or lack thereof of animal models in the form of drugs successfully brought to market and Pharma says it doesn’t work. Remember, Pharma is a business and they do not care how they develop new drugs they just want to develop new drugs so they can make money. Also remember that there are not two different theories of evolution: one for drug development and another for basic science research or basic research masquerading as applied research. If animal modeling in drug development fails to be consistent with evolutionary biology, then it fails in general as well.

Image courtesy of Wkipedia Common http://en.wikipedia.org/wiki/File:Chromosomes_mutations-en.svg

References

1.         Hunter, R.G. Alternatives to Animal Testing Drive Market: In Vivo and In Silico Methods from Predictive Toxicology to Help Develop Precision Medicine. 2014 January 2, 2014 [cited 2014 January 6]; Available from: http://www.genengnews.com/gen-articles/alternatives-to-animal-testing-drive-market/5095/.

2.         Herper, M. The Cost Of Creating A New Drug Now $5 Billion, Pushing Big Pharma To Change. 2013 August 11, 2013 [cited 2014 January 6]; Available from: http://www.forbes.com/sites/matthewherper/2013/08/11/how-the-staggering-cost-of-inventing-new-drugs-is-shaping-the-future-of-medicine/.

3.         Lin, J.H., Species similarities and differences in pharmacokinetics. Drug Metab Dispos, 1995. 23(10): p. 1008-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8654187

4.         Duyk, G., Attrition and translation. Science, 2003. 302(5645): p. 603-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14576424

5.         Kola, I. and J. Landis, Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov, 2004. 3(8): p. 711-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15286737

6.         McGee, P., Breeding Better Animal Models. Drug Discovery & Development, 2006(April): p. 18-23.

7.         Young, M., Prediction v Attrition Drug Discovery World, 2008(Fall): p. 9-12.

8.         Khanna, I., Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discovery Today, 2012. 17(19-20): p. 1088-102. http://www.ncbi.nlm.nih.gov/pubmed/22627006

9.         Morgan, P., et al., Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival. Drug Discovery Today, 2012. 17(9/10): p. 419-24.

10.       Paul, J.R., A History of Poliomyelitis. 1971, New Haven: Yale University Press.

11.       Editorial, Cold shower for AIDS vaccines. Nat Med, 2007. 13(12): p. 1389-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18064013

12.       Greek, R., Animal Models and the Development of an HIV Vaccine. J AIDS Clinic Res, 2012: p. S8:001. http://www.omicsonline.org/2155-6113/2155-6113-S8-001.php?aid=5787

13.       Broderick, J.P., The Challenges of Intracranial Revascularization for Stroke Prevention. New England Journal of Medicine, 2011. 365(11): p. 1054-1055. http://www.nejm.org/doi/full/10.1056/NEJMe1108394

14.       Chimowitz, M.I., et al., Stenting versus aggressive medical therapy for intracranial arterial stenosis. The New England journal of medicine, 2011. 365(11): p. 993-1003. http://www.ncbi.nlm.nih.gov/pubmed/21899409

15.       Donaghy, R.M.P. and M.G. Yasargil, Microvascular Surgery: Report of 1st Conference. 1968, New York: Kimpton.

16.       Powers, W.J., et al., Extracranial-Intracranial Bypass Surgery for Stroke Prevention in Hemodynamic Cerebral Ischemia. JAMA: The Journal of the American Medical Association, 2011. 306(18): p. 1983-1992. http://jama.ama-assn.org/content/306/18/1983.abstract

17.       The EC/IC Bypass Study Group, Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group. N Engl J Med, 1985. 313(19): p. 1191-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2865674

18.       Yasargil, M., Microsurgery Applied to Neurosurgery. 1969: Academic Press.

19.       Cooper, D.W., et al., Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology, 2002. 97(6): p. 1582-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12459688

20.       Whisnant, J.P., Cerebral Vascular Diseases. 1958: Grune and Stratton.

21.       Hain, R.F., P.V. Westhaysen, and R.L. Swank, Hemorrhagic cerebral infarction by arterial occlusion; an experimental study. J Neuropathol Exp Neurol, 1952. 11(1): p. 34-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14898307

22.       Anonymous, in Cerebrovascular Diseases : Proceedings of the Cerebrovascular Disease Conference 11th, Princeton, T.R. Price and E. Nelson, Editors. 1979, Raven Press.

23.       Laitinen, L.A., et al., Damage of the airway epithelium and bronchial reactivity in patients with asthma. The American review of respiratory disease, 1985. 131(4): p. 599-606. http://www.ncbi.nlm.nih.gov/pubmed/3994155

24.       Buckland, G.L., Harnessing opportunities in non-animal asthma research for a 21st-century science. Drug Discovery Today, 2011. 16(21/22): p. 912-927.

25.       Shanks, N. and R. Greek, Animal Models in Light of Evolution. 2009, Boca Raton: Brown Walker.

26.       Goldberg, M.E. Letter - Animal research key to advancing science 2014 January 5, 2014 [cited 2014 January 7]; Available from: http://host.madison.com/news/opinion/mailbag/animal-research-key-to-advancing-science----dr/article_89a888cf-9c47-5be0-a056-16da96118aab.html.