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Honesty in Academia

Sakai, writing in the alumni magazine of the University of Wisconsin stated: “Unlike clinical or translational research, where the direct intent is to improve health care, basic research such as Ganetzky’s aims simply to gain knowledge of the world and how it works, including the biology of the creatures living in it.” [1] Compare that statement to a press release titled Fast track to mouse modeling, which states:

What genes are responsible for the development of breast cancer? What are the brain cell mutations that lead to the onset of Alzheimer’s? To find new therapies, scientists have to understand how diseases are triggered at cell level. Experiments on genetically modified mice are an indispensable part of basic medical research. Now a method has been found to help laboratories carry out their work with fewer test animals. Scientists use genetically modified laboratory mice to investigate the underlying mechanisms of diseases. These “knockout” mice carry genes or gene regions that are thought to trigger diseases.

The press release then describes a technique to make genetically modified mice based on the paper by Wefers et al.[2] The press release heralds this as an animal protection breakthrough as: “Fewer laboratory animals [will be required] for basic medical research.”

As I may have mentioned, gene function varies among species. Finding out what function a gene has in a mouse is no guarantee that it will do the same in humans. It is at best a heuristic:

serving to indicate or point out; stimulating interest as a means of furthering investigation;

helping to learn;

guiding in discovery or investigation.

One must study humans in order to ascertain gene function in them. Monkeys also differ from humans in gene function [3, 4] and different strains of mice differ from each other.[5-7] Humans are being studied daily for gene function and, not surprisingly, this is yielding results applicable to humans. It does not however bring in grant money to the university.

I have written many times on the value of animal models in basic research. (See Is the use of sentient animals in basic research justifiable?) I have stated many times, as Sakai stated, that basic research, which “aims simply to gain knowledge of the world,” can be performed using animals. Many other uses of animals are also scientifically viable and many areas of basic research that did not involve animals have benefited humankind. (See FAQs About the Use of Animals in Science: A handbook for the scientifically perplexed and What Will We Do If We Don't Experiment On Animals? Medical Research for the Twenty-first Century.) There are myriad variations in types of basic research and there are almost as many different way to analyze the value and ethics of these endeavors. That having been said, no one, except the basic researchers that use animals, claims that animal-based basic science research or basic research in general is of predictive value for human patients.

Massimo Pigliucci recently wrote in his blog:

When I was a practicing evolutionary biologist, I had to constantly write grant proposals for the National Science Foundation, to keep my lab going and my graduate students and postdocs reasonably fed. NSF at one point started asking for a layperson statement of the proposed research, with the admirable goal of making the basic ideas available to the general public, who after all was footing the bill. NSF now also asks for a statement of broader impact, where the Principal Investigator has to explain why taxpayers should be paying for the usually highly esoteric research being proposed — often to the tune of hundreds of thousands, or even millions of dollars per year. Here is where things get funny: I noticed that both I and all my colleagues were stumped, and resorted to vague statements about the “long term implications” of basic research for scientific applications, eventually (way, way down the line) leading to potential applications concerning human health, the quality of the environment, and so on. But if pressed, we would have been in a really difficult position to elaborate on exactly how, say, studying the mating patterns of tropical butterflies, or the genetic structure of a species of small flowering plants, could plausibly be related to cures for cancer or any other kind of improvement to human life.

Indeed, on the rare occasions in which scientists are pressed on these matters they resort to the worst kind of evidence: anecdotes instead of rigorously quantified surveys of the connections between basic and applied research. Moreover, these anecdotes are often somewhat historically incorrect, since most scientists don’t actually have either the time or the inclination to read serious scholarly research in the history of their own field. So the last resort becomes something like, “well, this [i.e., my] topic of research is intrinsically interesting,” which means little more than that the person in question finds it fascinating and wants funding for it.

Before I leave room for misunderstanding, I do think that a healthy society ought to fund basic scientific research, just as it ought to fund the arts and the humanities.

I agree, basic research is important. (Pigliucci goes into more depth in the blog and I encourage everyone to read it in its entirety. I also highly reccommend his book, Nonsense on Stilts: How to Tell Science from Bunk) Moreover, ceteris paribus, animals can be successfully used in some areas of basic research. For example, scientists designed a robot that could walk on shifting sand by studying the walk of desert lizards.[8, 9] But some areas of basic research come with an ethical cost. If society understood the cost:benefit ratio of most uses of animal modeling in basic research, society would not allow such research to exist much less fund it. This is why universities and researchers routinely mislead society regarding the importance of animal models in basic research (see Is the use of sentient animals in basic research justifiable?).

David Gorski MD, PhD writing in his Science-Based Medicine blog addresses the issue of The NIH funding process: “Conformity” and “mediocrity”?

. . . progress in science-based medicine requires progress in science. That means all levels of biological (and even non-biological) basic science, which forms the foundation upon which translational science and clinical trials can be built. Without a robust pipeline of basic science progress upon which to base translational research and clinical trials, progress in SBM will slow and even grind to a halt.

The above is true in what it affirms but wrong in what it denies. Science-based discovery has led to wonderful advances. But serendipity and clinical observation have as well. Note what Marincola states regarding observation-based research:

The contemporary scientific establishment equates hypothesis testing to good science. This stance bypasses the preliminary need to identify a worthwhile hypothesis through rigorous observation of natural processes. If alleviation of human suffering is claimed as the goal of a scientific undertaking, it would be unfair to test a hypothesis whose relevance to human disease has not been satisfactorily proven. Here, we argue that descriptive investigations based on direct human observation should be highly valued and regarded essential for the selection of worthwhile hypotheses while the pursuit of costly scientific investigations without such evidence is a desecration of the cause upon which biomedical research is grounded. . . .

It is surprising how often a manuscript is dismissed by reviewers as "just descriptive", regardless of the novelty of the reported observation. On the other hand, we have not once received a negative comment on a "mechanistic" study, even if it lacks proof of the validity of the experimental model and its relevance to human disease. Such studies are automatically given the benefit of the doubt based on predictable rationalizations vaguely offered in the introductory paragraphs. As a consequence, innumerable conflicting results are published, each one a reflection of its own experimental bias. For example, in animal models, Interleukin-23 can either promote or hamper cancer growth; yet, information about its bio-availability in human cancers and its modality of expression, information that can potentially provide insight into the interpretation of such models, is limited. [10]

Many drugs, designed and developed based on data from animal models are successfully used every day by millions of people: just not for the purpose the animal models indicated. Many drugs were initially marketed for one use, failed for that use, but were serendipitously discovered to benefit patients for a different disease or condition. (See

Happy Accidents: Serendipity in Modern Medical Breakthroughs by Morton Meyers and

Who Goes First?: The Story of Self-Experimentation in Medicine by Lawrence Altman)

This brings me to my second point: the “science-based” discoveries in animals routinely fail to translate to humans. So Dr Gorski’s implied point, that we must fund everything that brings new knowledge about the material universe in order to have medical advances does not withstand scrutiny. First, no one seriously suggests experimenting on captive humans, despite the fact that such experimentation would bring new knowledge and that such knowledge would probably benefit patients. So ethical cost does play a role in what gets funded and what does not.

Second, when a practice has been analyzed and has a track record for success as poor as recent animal-based research has, it should be abandoned. There are scientific reasons for the poor track record and, just as Dr Gorski likes to discuss prior plausibility (and rightly so), so too should a research practice’s track record inform society regarding what to fund and what not to fund. I would not fund ESP research despite the claim by practitioners that any day now it will prevent all disease. I would not fund research on touch therapy or homeopathy because they are based on pre-science beliefs that have been shown nonsensical. But if one is to go down the prior plausibility road (and I think society should), then one must be consistent. Evolutionary biology and complex systems theory show that interspecies extrapolation for response to drugs and disease is just as nonsensical as water retaining the essence of various molecules.

Gorski continues:

That’s why, in the U.S., the National Institutes of Health (NIH) is so critical. The NIH funds large amounts of biomedical research each year, which means that what the NIH will and will not fund can’t help but have a profound effect shaping the pipeline of the basic and preclinical research that ultimately leads to new treatments and cures. Moreover, NIH funding has a profound effect on the careers of biomedical researchers and clinician-scientists, as having the “gold standard” NIH grant known as the R01 is viewed as a prerequisite for tenure and promotion in many universities and academic medical centers.

The above is true. Which is why I harp on the funding policies of NIH. NIH is the primary influence in research direction: what gets funded and what does not. Should NIH ever acknowledge that animal models are funded only for the sake of obtaining more knowledge of the material universe, and that no one expects them to lead to cures or treatments for patients, then other granting bodies would have to change their practice as well. This would be the death knell for a vast majority of animal-based research and free money for universities.

Statements like the above from Sakai and similar ones from famous scientists  (See Is the use of sentient animals in basic research justifiable?) must be painful to the animal model community. During this time of fiscal constraint, just when the animal model community needs support, people state the obvious: animal models as used in basic research are not of predictive value for human response to drugs and disease. How are animal modelers supposed to keep obtaining grants if UW admits that all the promises made in those grant applications are lies?


1.         Sakai, J (2012) Lord of the flies. On Wisconsin:25-29.

2.         Wefers, B, M Meyer, O Ortiz et al. (2013) Direct production of mouse disease models by embryo microinjection of TALENs and oligodeoxynucleotides. Proceedings of the National Academy of Sciences 110:3782-3787. 10.1073/pnas.1218721110.

3.         Gibbs, RA, J Rogers, MG Katze et al. (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222-234. 316/5822/222 [pii] 10.1126/science.1139247.

4.         Holmes, B (2007) Monkey genome springs surprise for human origins. New Scientist:15.

5.         Belmaker, R, Y Bersudsky, G Agam (2012) Individual differences and evidence-based psychopharmacology. BMC Medicine 10:110. 10.1186/1741-7015-10-110.

6.         Morange, M (2001) A successful form for reductionism. The Biochemist 23:37-39.

7.         Pearson, H (2002) Surviving a knockout blow. Nature 415:8-9. 10.1038/415008a 415008a [pii].

8.         Raffensperger, L (2013) Robot Designed to Run Like a Lizard Over Sand. Discover Magazine, March 22 - .UUySJmAd7iM

9.         Hunt, ML (2013) Applied physics. Robotic walking in the real world. Science 339:1389-1390. 10.1126/science.1235276.

10. Marincola, FM (2007) In support of descriptive studies; relevance to translational research. J Transl Med 5:21. 1479-5876-5-21 [pii] 10.1186/1479-5876-5-21.


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