On July 31, 2013, Chris (that’s the name he posted under) AKA Blue Sky Science wrote an essay on the Speaking of Research site titled: “You can fool some of the MPs all of the time…”. As the essay criticizes some of my positions I will comment on it here.
Chris’s issue revolves around an Early Day Motion (EDM) in the UK parliament. As I am not an expert on UK politics and procedures, I will leave that aspect of the essay to others and simply address Chris’s criticism of my position. Before I do that however, I will state once again that the organization that apparently advocated for the EDM, Friends for Life on Earth (FLOE) is not associated with me despite the fact that they advocate for my position and use my articles and books to make their case. I know some of the people at FLOE but have no position or power in the organization. I appreciate their efforts and use of my publications but that is the extent of it.
The first specific point Chris takes issue with is my quoting the US National Cancer Institute regarding animal models. Here is the quote with the material before and after the relevant part:
Pharmaceutical companies often test drug candidates in animals carrying transplanted human tumors, a model called a xenograft. But not only have very few of the drugs that showed anticancer activity in xenografts made it into the clinic, a recent study conducted at the National Cancer Institute (NCI) also suggests that the xenograft models miss effective drugs. The animals apparently do not handle the drugs exactly the way the human body does. And attempts to use human cells in culture don't seem to be faring any better, partly because cell culture provides no information about whether a drug will make it to the tumor sites.
The pressure is on to do better. So researchers are now trying to exploit recent discoveries about the subtle genetic and cellular changes that lead a cell toward cancer to create cultured cells or animal models that accurately reproduce these changes. "The real challenge for the 1990s is how to maximize our screening systems so that we are using the biological information that has accumulated," says Edward Sausville, associate director of the division of cancer treatment and diagnosis for the developmental therapeutics program at the NCI. "In short, we need to find faithful representations of carcinogenesis." 
A theme of Chris’s article is that because the quotes and or data (regarding either toxicity or anti-neoplastics) are old, they are therefore invalid. The age of data and quotes can be relevant, especially if new developments have occurred that invalidate the data or concept. But Chris offers no new data. This is because the positions he criticized have either no new data to refute the old or the new data supports the old. The reality of current cancer research is the same as it was in 1997 when the above was published by Science. Roughly 5% of new cancer drugs pass human clinical trials after passing safety and efficacy testing in animals.[2-4] This means the predictive value of animal models is nil. Whether a drug cures or kills an animal is immaterial to the safety and efficacy in humans. (There are exceptions to this, such as if the drug kills by means that are best described by physics or physicochemical properties. In other words sulfuric acid is bad for you.) Moreover, scientists continue to question whether society has lost cures and treatments because drugs from numerous categories failed animal tests. The new animal models that have been used since 1997 have not been any better than the old ones. [3, 6-15] See [16-23] for support from theory on why this is the case. (I have made the same case regarding toxicity, Chris’s other issue in the essay, relying largely on studies still accepted by Pharma in addition to quotes from scientists directly involved with Pharma acknowledging that animal models are not predictive for toxicity. [3, 7, 16, 24-46].)
I have stated many times that Pharma needs predictive tools. This is the case for discovering cancer drugs as well. Neither in vitro nor in vivo qualifies as having predictive value for chemotherapies in terms of safet or efficacy. This lack of predictive value for in vitro and in silico does not justify using animal models. 1) Contrary to what Chris implies, vivisection activists base their justification for using animals on their predictive value.[26, 47-55] They just don’t know what the phrase means. I do not know of any “in vitro activists” that do this. In fact, I don’t know of any in vitro activists. Vivisection activists lobby Congress, not scientists that use in vitro methods as they use in vitro as tool, not a method to pay their mortgage and fund the university. 2) A method or practice either has predictive value or it does not. Regardless of where one draws the line for predictive value, say a PPV and NPV of 0.9 or 0.8 or 0.75, animal models do not come anywhere close to this value and hence are not predictive and hence should not be sold to society as having predictive value.
I have provided references before regarding what constitutes predictive value in medical science.[17 ] I have stated that somewhere in the 0.9 neighborhood is needed and provided references supporting this. Granted, some tests in medicine are used despite not being that high. This is because these tests are the best we have and sick patients and their physicians are doing the best they can. Drug development is in a different category in terms of expediency and have more options—like human-based testing. There is no excuse for using animal models in drug development unless you are also advocating for using Ouija boards and a random number generator. Moreover, physicians fully realize the fact that some tests are not great and take this into consideration when determining care recommendations. One does not, however hear physicians advocating for tests that have a PPV of 0.5. Nevertheless, here [57-61] are some references comparing PPVs that support the 0.9 neighborhood value. Further, what constitutes predictive value will vary based on circumstances. Whether to operate on a potential hot appendix will require a different predictive value that whether to use drug-sniffing dogs in airports. Ask any physician if a PPV in the 0.3-0.5 (the numbers one sees with animal testing) area has predictive value and the answer will be no. Finally, regardless of what the exact number is for predictive value, most people actually involved in drug development agree that animal tests do not come close to that value. [3, 7, 16, 24-46]. (Interestingly, Chris refers to the fact that homeopathy is offered by the NHS as an example of why PPV is unimportant. NHS is a government agency not a scientific one and as such the fact that NHS offers voodoo is not relevant to the discussion.)
Finally, Chris’s criticisms, while disingenuous IMO, are good examples of what one should expect and not expect from reading a blog. I reference most of the controversial statements in my blog but do not usually reference noncontroversial statements. Therefore the vivisection activist must manufacture a controversy—such as the exact value for predictive value in medical science—or ignore the references that explain and prove the points in depth. The scientifically under-educated will not realize the difference between a manufactured controversy and a real one hence my position will be called into doubt. This brings me back to a theme in my blogs, articles, and interviews: if you want to discuss science intelligently, you must read the relevant material. There is far too much knowledge needed to participate in science discussions in general and animal model discussions specifically to rationally expect a 2000 word blog to provide enough of that data, education regarding science in general, and that degree of explanatory power. If a person does not have doctorate in science, it will be very difficult to become an expert in scientific areas like animal models. Even some with a doctorate fail to understand the relevant concepts, although how much of that failure is feigned is debatable. This is why I frequently reference books and articles I have written that go into more depth, along with article by others that support my position. However, even that is insufficient to convince a man whose livelihood and ego are wrapped up in animal models.
This is one reason I repeatedly request that vivisection activists debate me in the scientific literature. Referees from science journals would be asked to judge validity and fallacious reasoning and so forth. I have nothing to fear from a fair critique of my position. That is why I have over a dozen article published in peer-reviewed science journals that specifically address animal modeling theory. Most vivisection activists do not have this record. They say they rely on past article regarding the importance of animal models but this is unacceptable as 1) most of these articles have not been critiqued specifically for the value of the animal model in the development or discovery (for examples see [40, 43, 44, 62-64] and 2) the reasoning used by most articles supporting animal models is an example of post hoc ergo propter hoc. There are numerous on-line only, open access journals that would publish a lengthy debate between a vivisection activist and me, along with comments from the referees. The only reason such a debate does not happen is the lack of participation by a vivisection activist. A public debate could also easily involve a peer-review format with judges and a moderator with actual power to hold the participants accountable for fallacies, misleading or false statements, and lack of evidence.
I won’t be holding my breath waiting for this to happen.
Photo from EveryStockPhoto
1. Gura, T., Cancer Models: Systems for identifying new drugs are often faulty. Science, 1997. 278(5340): p. 1041-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9381203
2. Kummar, S., et al., Compressing drug development timelines in oncology using phase '0' trials. Nature reviews. Cancer, 2007. 7(2): p. 131-9. http://www.ncbi.nlm.nih.gov/pubmed/17251919
3. Cook, N., D.I. Jodrell, and D.A. Tuveson, Predictive in vivo animal models and translation to clinical trials. Drug Discovery Today, 2012. 17(5/6): p. 253-60.
4. Roberts, T.G., Jr., et al., Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. JAMA : the journal of the American Medical Association, 2004. 292(17): p. 2130-40. http://www.ncbi.nlm.nih.gov/pubmed/15523074
5. Lazzarini, L., et al., Experimental osteomyelitis: what have we learned from animal studies about the systemic treatment of osteomyelitis? J Chemother, 2006. 18(5): p. 451-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17127219
6. Editors, Nic Jones. Nat Rev Drug Discov, 2011. 10(4): p. 252-252. http://dx.doi.org/10.1038/nrd3416
7. Zielinska, E., Building a better mouse. The Scientist, 2010. 24(4): p. 34-38.
8. Brennan, R., S. Federico, and M.A. Dyer, The war on cancer: have we won the battle but lost the war? Oncotarget, 2010. 1(2): p. 77-83. http://www.ncbi.nlm.nih.gov/pubmed/20877440
9. Wade, N., New Treatment for Cancer Shows Promise in Testing, in New York Times2009: New York.
10. DiMasi, J.A. and H.G. Grabowski, Economics of new oncology drug development. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2007. 25(2): p. 209-16. http://www.ncbi.nlm.nih.gov/pubmed/17210942
11. DiMasi, J.A., et al., Trends in risks associated with new drug development: success rates for investigational drugs. Clinical Pharmacology and Therapeutics, 2010. 87(3): p. 272-7. http://www.ncbi.nlm.nih.gov/pubmed/20130567
12. Kerbel, R.S., Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol. Ther., 2003. 2(4 Suppl 1): p. S134-9.
13. Peterson, J.K. and P.J. Houghton, Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development. Eur. J. Cancer, 2004. 40: p. 837-844. http://dx.doi.org/10.1016/j.ejca.2004.01.003
14. Talmadge, J.E., et al., Murine Models to Evaluate Novel and Conventional Therapeutic Strategies for Cancer. Am. J. Pathol., 2007. 170: p. 793-804. http://dx.doi.org/10.2353/ajpath.2007.060929
15. Francia, G. and R.S. Kerbel, Raising the bar for cancer therapy models. Nat Biotech, 2010. 28(6): p. 561-562. http://dx.doi.org/10.1038/nbt0610-561
16. Greek, R., A. Menache, and M.J. Rice, Animal models in an age of personalized medicine. Personalized Medicine, 2012. 9(1): p. 47-64. http://dx.doi.org/10.2217/pme.11.89
17. Greek, R. and M.J. Rice, Animal models and conserved processes. Theoretical Biology and Medical Modelling, 2012. 9(40). http://www.tbiomed.com/content/9/1/40/abstract
18. Greek, R., Animal Models of Cancer in Light of Evolutionary Biology and Complexity Science, in The Research and Biology of Cancer. 2013, iConcept Press: Hong Kong. http://www.iconceptpress.com/www/site/papers.webView.php?publicationID=BK030A
19. Greek, R., Animal Models in Drug Development, in New Insights into Toxicity and Drug Testing, S. Gowder, Editor. 2013, InTech: Manhattan. p. 124-152. http://www.intechopen.com/books/new-insights-into-toxicity-and-drug-testing/animal-models-in-drug-development
20. Greek, R. and L. Hansen, The Strengths and Limits of Animal Models as Illustrated by the Discovery and Development of Antibacterials. Biological Systems: Open Access, 2013. 2(2): p. 109. doi: 10.4172/BSO.1000109 http://www.omicsgroup.org/journals/BSO/BSO-2-109.php?aid=14441
21. Greek, R. and L.A. Hansen, 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: p. http://dx.doi.org/10.1016/j.pbiomolbio.2013.06.002. http://www.sciencedirect.com/science/article/pii/S0079610713000539
22. Greek, R. and A. Menache, Systematic Reviews of Animal Models: Methodology versus Epistemology. Int J Med Sci 2013. 10(3): p. 206-221. http://www.medsci.org/v10p0206.htm
23. Jones, R.C. and R. Greek, A Review of the Institute of Medicine's Analysis of using Chimpanzees in Biomedical Research. Sci Eng Ethics, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23616243
24. Fletcher, A.P., Drug safety tests and subsequent clinical experience. J R Soc Med, 1978. 71(9): p. 693-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=712750
25. Sietsema, W.K., The absolute oral bioavailability of selected drugs. Int J Clin Pharmacol Ther Toxicol, 1989. 27(4): p. 179-211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2654032
26. Heywood, R., Clinical Toxicity--Could it have been predicted? Post-marketing experience., in Animal Toxicity Studies: Their Relevance for Man, CE Lumley and S. Walker, Editors. 1990, Quay: Lancaster. p. 57-67.
27. Lumley, C., Clinical toxicity: could it have been predicted? Premarketing experience, in Animal Toxicity Studies: Their Relevance for Man, C. Lumley and S. Walker, Editors. 1990, Quay: London. p. 49-56.
28. Suter, K., What can be learned from case studies? The company approach., in Animal Toxicity Studies: Their Relevance for Man, C. Lumley and S. Walker, Editors. 1990, Quay: Lancaster. p. 71-8.
29. Horrobin, D.F., Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat Rev Drug Discov, 2003. 2(2): p. 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12563306
30. Weaver, J.L., et al., Detection of systemic hypersensitivity to drugs using standard guinea pig assays. Toxicology, 2003. 193(3): p. 203-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14599760
31. 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
32. FDA. FDA Issues Advice to Make Earliest Stages Of Clinical Drug Development More Efficient. 2006 June 18, 2009 [cited 2010 March 7]; FDA News Release]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108576.htm.
33. O'Collins, V.E., et al., 1,026 experimental treatments in acute stroke. Ann Neurol, 2006. 59(3): p. 467-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16453316
34. Dixit, R. and U. Boelsterli, Healthy animals and animal models of human disease(s) in safety assessment of human pharmaceuticals, including therapeutic antibodies. Drug Discovery Today, 2007. 12(7-8): p. 336-42.
35. Wall, R.J. and M. Shani, Are animal models as good as we think? Theriogenology, 2008. 69(1): p. 2-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17988725
36. Greek, R. and N. Shanks, FAQs About the Use of Animals in Science: A handbook for the scientifically perplexed. 2009, Lanham: University Press of America.
37. Markou, A., et al., Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. 34(1): p. 74-89. http://www.ncbi.nlm.nih.gov/pubmed/18830240
38. Shanks, N. and R. Greek, Animal Models in Light of Evolution. 2009, Boca Raton: Brown Walker.
39. Shanks, N., R. Greek, and J. Greek, Are animal models predictive for humans? Philos Ethics Humanit Med, 2009. 4(1): p. 2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19146696
40. Greek, R. and J. Greek, Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med, 2010. 5: p. 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20825676
41. M.E., In This Issue. Models that better mimic human cancer. Nature Biotechnology, 2010. 28(1): p. vii.
42. Collins, F.S., Reengineering Translational Science: The Time Is Right. Science Translational Medicine, 2011. 3(90): p. 90cm17. http://stm.sciencemag.org/content/3/90/90cm17.abstract
43. Greek, R., L.A. Hansen, and A. Menache, An analysis of the Bateson Review of research using nonhuman primates Medicolegal and Bioethics 2011. 1(1): p. 3-22. http://www.dovepress.com/an-analysis-of-the-bateson-review-of-research-using-nonhuman-primates-peer-reviewed-article-MB
44. Greek, R., N. Shanks, and M.J. Rice, The History and Implications of Testing Thalidomide on Animals. The Journal of Philosophy, Science & Law, 2011. 11(October 3). http://www6.miami.edu/ethics/jpsl/archives/all/TestingThalidomide.html
45. Sharp, P.A. and R. Langer, Promoting Convergence in Biomedical Science. Science, 2011. 333(6042): p. 527. http://www.sciencemag.org/content/333/6042/527.short
46. Drake III, D.R., et al., In Vitro Biomimetic Model of the Human Immune System for Predictive Vaccine Assessments. Disruptive Science and Technology, 2012. 1(1): p. 28-40.
47. Rudczynski, A.B., Letter, in New Haven Register2011: New Haven.
48. Buckland, D. The extraordinary secret of how mice are curing cancer. 2013 June 9, 2013 [cited 2013 July 31]; Available from: http://www.express.co.uk/news/health/406168/The-extraordinary-secret-of-how-mice-are-curing-cancer.
49. McKie, R. Animal activists' terror tactics drive staff out of laboratories. 2012 July 28 [cited 2012 July 30]; Available from: http://www.guardian.co.uk/science/2012/jul/29/animal-activists-terror-tactics-harlan-laboratories-staff?newsfeed=true.
50. Vassar, R., Alzheimer's therapy: a BACE in the hand? Nat Med, 2011. 17(8): p. 932-933. http://dx.doi.org/10.1038/nm0811-932
51. Anonymous, Of Mice...and Humans. Drug Discovery and Development, 2008. 11(6): p. 16-20. http://www.dddmag.com/Article-Humanized-Rodent-Models-Increase-Applicability-of-Animal-Testing-Data.aspx
52. Wellcome Trust Sanger Institute. Researchers develop mouse genetic blueprint. Mouse study drives forward understanding of human biology. 2011 September 14 [cited 2011 October 6]; Available from: http://www.sanger.ac.uk/about/press/2011/110914.html.
53. Fomchenko, E.I. and E.C. Holland, Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res, 2006. 12(18): p. 5288-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17000661
54. Gad, S., Preface, in Animal Models in Toxicology, S. Gad, Editor. 2007, CRC Press: Boca Raton. p. 1-18.
55. Giles, J., Animal experiments under fire for poor design. Nature, 2006. 444(7122): p. 981. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17183281
56. Buzoni-Gatel, D., et al. Animal Models and Relevance/Predictivity: how to better leverage the knowledge of the veterinarian field. 2011 [cited 2011 October 6]; Available from: http://www.fondation-merieux.org/documents/conferences-and-events/2011/animal-models-and-relevance-predictivity-10-12-october-2011-programme.pdf.
57. Zhang, S., et al., Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma. World J Gastroenterol, 2008. 14(23): p. 3750-3753.
58. Sasson, C., et al., Prehospital Termination of Resuscitation in Cases of Refractory Out-of-Hospital Cardiac Arrest. JAMA: The Journal of the American Medical Association, 2008. 300(12): p. 1432-1438. http://jama.ama-assn.org/content/300/12/1432.abstract
59. Salekin, R.T., et al., Psychopathy and recidivism among female inmates. Law and Human Behavior, 1998. 22: p. 109-128.
60. Mayanja, B.N., et al., Using verbal autopsy to assess the prevalence of HIV infection among deaths in the ART period in rural Uganda: a prospective cohort study, 2006-2008. Population Health Metrics, 2011. 9: p. 36.
61. Santos, G., et al., Predictive values at risk of falling in physically active and no active elderly with Berg Balance Scale. Rev Bras Fisioter, 2011. 15(2): p. 95-101.
62. 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
63. Greek, R. and L.A. Hansen, The Development of Deep Brain Stimulation for Movement Disorders. J Clinic Res Bioeth, 2012. 3.
64. Greek, R., A. Pippus, and L.A. Hansen, The Nuremberg Code subverts human health and safety by requiring animal modeling. BMC medical ethics, 2012. 13(1): p. 16. http://www.ncbi.nlm.nih.gov/pubmed/22769234