One reason animal models do not predict human response to drugs and disease is the fact that humans themselves vary in these responses. One reason humans vary, lies in evolutionary biology and genetics. This is also why humans respond differently than animal models. This is illustrated by the following.
Emily Waltz reported in Nature Biotechnology that clinical studies revealed that the RV144 vaccine offered some protection to patients with a certain genotype but increased risk for another genotype. Wald: “After analyzing blood samples collected from volunteers in the trial, the researchers identified two antibody responses: one correlated with a reduced risk of HIV infection, and the other with an increased risk. In the first case, vaccinated trial participants whose blood contained an IgG antibody that recognizes a portion of HIV's outer envelope—the V2 loop—were 43% less likely to acquire HIV than volunteers whose immune systems did not generate this antibody response. In the second, vaccinated volunteers in the trial who developed IgA antibodies that targeted the HIV envelope were 54% more likely to become HIV infected, suggesting that these antibodies reduced the protective effect of the vaccines.” (Waltz 2012)
Other protective antibodies have been found. Wald continues: “The protective antibody identified in patient analysis of the RV144 trial joins several broadly neutralizing antibodies, isolated from HIV-infected people around the world, which are highly potent against HIV. They are also capable of blocking a broad range of HIV variants—a key to vaccine development, as HIV is wildly mutable. In addition to the virus-neutralizing antibodies PG9, PG16 and VRC01 reported in Science (326, 285–289, 2009; Science 329, 811–817, 2010), 17 novel broadly neutralizing antibodies (some of which were 10–100 times more potent than PG9, PG16 and VRC01) were reported in Nature last August (Nature 477, 466–470, 2011).” (Waltz 2012)
This HIV vaccine is not the only one to which humans vary in their response. (Hennig et al. 2008; Newport, Goetghebuer, and Marchant 2005; Newport et al. 2004)
Western lowland gorillas have about the same number of genes as humans, ~21,000. (Scally et al. 2012) Scally et al. found that ~30% of the gorilla genome is more closely related to the human or chimpanzee genome than the chimpanzee and human genomes are related to each other despite the fact that the line leading to gorillas split off before the line leading to chimpanzees and humans. Moreover, after the chimp-human ancestor split from gorilla, ~500 genes changed very rapidly. These 500 genes appear to be involved in hearing and brain development. Many of these 500 genes also changed rapidly after the human-chimpanzee split. Yet, these genes are almost identical in humans and gorillas (a phenomenon called incomplete lineage sorting (Gibbs and Rogers 2012)) thus calling into question whether they alone can account for some of the differences between the brains of humans and gorillas.
Even though the gorilla genome has similarities to the human genome, the way these genes are regulated and expressed, the presence of modifier genes, and other differences entail that a drug might be lethal for a human but curative for a gorilla. Just as another drug might be helpful for one human but harmful for another. Furthermore, gorillas and humans are examples of living adaptive complex systems; hence we should expect different results from the same perturbation to the system. Put all of this in the context of the following.
In volume 8, issue number 1, from January 2011, “Report on Research Compliance: News and Analysis for Colleges, Universities and Teaching Hospitals” published an article Atlantic Information Services, Inc concerning the use of animal in research and the opposition to this use. The following four paragraphs are from page 4 of the article.
“There is a growing idea that the work is not valuable at all,” Ringach said. Referring to the survey Jentsch cited, Ringach said that “many of the people who answered that the work [animal experimentation] is unethical did so with the belief that the work actually does not help to move medical human research forward, that we are just animal researchers because of other considerations…it brings money to the university, because it pays our salaries, and that’s about it.”
Given this, “explaining the science is critical,” Ringach said. “If we don’t get the scientific facts right, we are not on the same page. It is very difficult to have the ethical discussion. When we are challenged with explaining why the work is ethical, we can’t just reply that all of our research is done according to the regulations [of the Animal Welfare Act and the institution]. That’s not the ethical explanation. We have to add a good ethical reason for justifying the research,” he said.
Ringach said the goal of dialogue is to not only justify the research to those who may question it but to possibly deflate the argument of extremists.
“If we engage in such a dialogue, I think there’s a chance — and this is just a hope — that this will make the lives of these small groups that advocate violence more difficult because they are not just going to be able to point to us and say ‘they don’t want to talk,’” Ringach said.
Let me say this very clearly: Dr Ringach and company don’t want to talk. At least not to anyone that can refute the nonsense that they claim their ethics argument is based on. What Dr Ringach means by “dialogue” is hawking the use of animals in research to people who are not in possession of the facts and avoiding like the plague actually debating the issue with anyone that can point out his fallacies, distortions, misinformation, and propaganda. Think I am exaggerating about their situation? Julia Schulhof and Emily Poe, editors of Lab Animal write about the importance of “marketing”, “spin control” and “selling” animal experimentation to the taxpayer. (Schulhof and Poe 2000) Jayne Mackta of the New Jersey Association for Biomedical Research also stated in Lab Animal: “Central to every story…must be a positive yet simple statement celebrating the role of animals in the process…Let’s use every opportunity to score points with the public.”(Mackta 2000) The vested interest groups are not purveyors of truth.
Dr Ringach and indeed essentially everyone from the animal model community will not debate me, solely and specifically on the scientific issues surrounding the use of animals in research. They will not debate me in universities, they will not debate me in the scientific literature where such debates are common, they will not answer specific questions in their blogs or other writings, they will not in any way, shape, or form do anything other than force-feed society the half-truths and outright lies that are the party line. Because they do not comprehend the difference between a hypothesis and a theory, they hope society will not know the difference between a claim and a fact. They will write and speak about all the wonderful advances in medicine supposedly made because of animal models but they will not make an argument that can then be challenged. They will simply repeat their talking points many times and hope society then believes it all because people have heard it all stated so frequently.
All of this is great marketing but lousy science. Indeed it is highly unethical. But the vested interest groups that profit from the animal model do not care about this. Universities are just as much to blame as the researches. Universities today are not the bastions of integrity, knowledge, and truth that they were decades ago. Today, universities will stop at nothing to bring in money. The James Randi Educational Foundation announced its 2012 Pigasus Awards, which are awarded to the promoters of the worst nonsense. One of the winners was Syracuse University (SU), which sponsors facilitated communication (FC). (See here and here for more on FC.) Why does SU promote FC after it has been definitively refuted? Because they make money from it. The same is true about universities that sell “Integrative Medicine.” Acupuncture, Traditional Chinese Medicine, herbal remedies, guided imagery, and Reiki are not going to cure what ails you but they do bring in the dollars. (For more about “Integrative Medicine” see here, here, and here.)
Individual humans vary in their response to drugs and disease. The genetic make-up of individual humans varies but not as profoundly as it does from other species. Even when humans and animals have the same genes the way those genes are regulated and expressed can be the difference between a life-saving drug and a life-threatening one. Sadly, ethics also varies among humans. When scientists and universities contravene science in the pursuit of money, society should act. Vested interest groups cannot be trusted. It is time society accepts the fact that universities and scientists are just another vested interest group.
Gibbs, Richard A., and Jeffrey Rogers. 2012. Genomics: Gorilla gorilla gorilla. Nature 483 (7388):164-165.
Hennig et al. 2008. Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS ONE 3 (3):e1898.
Mackta, Jayne. 2000. The Case for Communication. Lab Animal 29 (2):38-41.
Newport, M. J., T. Goetghebuer, and A. Marchant. 2005. Hunting for immune response regulatory genes: vaccination studies in infant twins. Expert Rev Vaccines 4 (5):739-46.
Newport, M. J., T. Goetghebuer, H. A. Weiss, H. Whittle, C. A. Siegrist, and A. Marchant. 2004. Genetic regulation of immune responses to vaccines in early life. Genes Immun 5 (2):122-9.
Scally et al. 2012. Insights into hominid evolution from the gorilla genome sequence. Nature 483 (7388):169-175.
Schulhof, Julia, and Emily Poe. 2000. Editorial. Lab Animal 29 (2):9.
Waltz, Emily. 2012. HIV neutralizing antibodies reignite interest in vaccine. Nat Biotech 30 (3):204-205.