Animal Rights

Elias Zerhouni

| by Dr Ray Greek

Elias Zerhouni was director of the NIH from 2002 to 2008 and is known for his “Roadmap for Medical Research” initiative, “New Pathways to Discovery,” and “Re-engineering the Clinical Research Enterprise.” These laid the pathway for The National Center for Advancing Translational Sciences (NCATS). After he retired from NIH in 2008, Zerhouni became President of Global R&D at Sanofi.

Neil Munro published an article in the National Journal in 2003, in which he quoted Zerhouni:

In the six years since 1997, Congress has doubled the National Institutes of Health's medical-science budget, which this year stands at almost $28 billion. Now Congress wants results. The money flows to scientists at NIH and also to research centers scattered throughout legislators' districts. The rising tide of funds has helped to boost many local economies, but, so far, the money has produced limited benefits for patients, in part because scientists direct so much of it to their colleagues for basic research. NIH's research promises a big payoff someday, but, given the complexity of human biology, converting hopes into therapies can take 10, 15, or even 20 years. . . . Zerhouni [NIH Director Elias Zerhouni] is also keenly aware of the complaints from Gregg, Ambler, and many others about the slow conversion of science into health care. The answer, he said, “is not so much a question of incentives, [but rather] removing the obstacles.” Still, NIH will remain focused on science, not therapies, he said. “We're not changing the balance, we're supercharging the NIH.” [1] (Emphasis added)

Philips wrote in New Scientist in 2004:

There is increasing recognition that basic research doesn't just flow automatically into clinical treatments and that both basic researchers and clinicians have to change the way they work to make this happen more readily. . . . The challenge of translating basic science into treatments is particularly acute in the neurosciences. But the same kinds of problems crop up in all fields of biomedicine. In March this year [this is during Zerhouni’s tenure at NIH], the US Food and Drug Administration (FDA) issued a white paper outlining its "critical path initiative" exploring how translational research might be improved. The report highlighted a "growing crisis" caused by the slowdown in the production of new therapies. The crux of the problem lies with the applied sciences, which have not kept pace with the basic sciences, the report concludes. The tools of the last century - animal toxicology and human tests - may need to be replaced or supplemented with newer technologies. We are not getting better at identifying potentially suitable drug candidates. Using genomics, imaging, proteomics and bioinformatics studies to help screen drug candidates for safety and efficacy early on could help improve the process. ( (Longer URL))

. . . These plans have been widely welcomed, but there are still some problems specific to neuroscience. "The biomedical model is failing," says Susan Fitzpatrick, vice-president of the James S. McDonnell Foundation in Saint Louis, Missouri. Basic biomedical research relies heavily on animal models, especially rats and mice, but she thinks it may be necessary to rethink this approach if treatments for brain diseases are going to reach the patients who need them.

Even if we know all there is to know about the animal model we don't necessarily know about the disease, Fitzpatrick says. "The model becomes what we study, not the human disease." And while this is a problem in all areas of disease, nowhere is it more acute than in brain disease. Kidney, liver or heart function is basically the same in different animal models, but the human brain is different. "It is not a chimp brain or a monkey brain or a mouse brain. It is very, very different."

Take brain cancer. The traditional model for studying brain cancer is to take human cancer cells, sometimes tissue-cultured into cell lines, and transplant them under the skin of an immunosuppressed mouse. This approach ignores the fact that cancer is a disease of context: as soon as you change the environment you will change those cells. "Any agent you test is probably unlikely to be effective when you have a tumour in context," Fitzpatrick says. "It's a fundamental flaw. We need a fundamentally new approach." [2] (Emphasis added.)

Zerhouni appears to be what he calls “science-oriented” in 2003, not therapies-oriented. But he appears to be rethinking the issue in 2005:

At no other time has the need for a robust, bidirectional information flow between basic and translational scientists been so necessary. Advances in our understanding of biologic systems and the development of powerful new tools that can be applied at both the bench and the bedside — genomics, proteomics, transgenic animal models, structural biology, biochemistry, and imaging technologies — offer unprecedented prospects for advancing knowledge of human disorders in a translational context. Moreover, it has also become clear that available animal models of human disease are often inadequate, necessitating even more research on human populations and biologic samples. [3] (Emphasis added.)

Mullane and Williams reinforce Philips and others in stating the following in 2012:

Although there has been an unprecedented growth in scientific knowledge that has been accompanied with enormous research investments in academia, federal research laboratories and the pharmaceutical and/or biotechnology industries, which reached US$150 billion in 2010 [3], new drug introductions over the past decade have stagnated [4,5]. Indeed, the 5% success rate of compounds entering clinical trials [3] continues to impact the successful development of new and improved therapeutics, especially for chronic diseases, such as diabetes and Alzheimer’s disease (AD), that require lifelong treatment and for which the incidence is growing exponentially such that they have the potential to bankrupt healthcare systems worldwide in the absence of effective treatment options.

A recent increase in drug approvals by the US Food and Drug Administration (FDA), with 35 new, innovative and ‘many groundbreaking’ medicines approved to date during fiscal 2011, more than a 50% increase over the number accepted in 2010, . . . has been heralded [6] as a ‘refill. . .[ing of]. . .parched pipelines’, a ‘payoff from a research reorientation. . .[undertaken]. . .several years ago’. This view is not shared by seasoned industry observers [and here] . . . who question whether these increases are indicative of getting the R&D model ‘right’, instead ascribing the numbers to increased business development activity and licensing of late-stage development compounds, and ‘clearer FDA guidance’. Although news of the increase in drug approvals is welcome, it should be viewed in the context of the proverb, ‘a swallow doth not a summer make’ as drug approvals over the past 6 years have averaged 22 per year as compared to 36 per year in the previous 9 years (Fig. 1) . . . [see here and here]. . . . The architect of the NIH Roadmap [Elias Zerhouni], now head of R&D at Sanofi and consequently exposed to the practical challenges of the real world of drug discovery, recently noted that there are ‘no simple solutions’ to the challenges of translational research and ‘that such ‘‘bench to bedside’’ research is more difficult than. . .[I]. . .thought.’ [4]

Others have noticed this phenomena. Contopoulos-Ioannidis et al. [5] quantified the translation rate (hence the term translational research) of “highly promising” basic research into clinical applications. They published a study in the American Journal of Medicine in 2003 that revealed of 101 basic research papers published in high-profile journals between 1979 and 1983, 27 led to randomized clinical trials and only 5 eventually gave rise to licensed clinical application. (Also see [6].)

Crowley commented on the article:

The article by Contopoulos-Ioannidis et al. in this issue of the journal addresses a much-discussed but rarely quantified issue: the frequency with which basic research findings translate into clinical utility. The authors performed an algorithmic computer search of all articles published in six leading basic science journals (Nature, Cell, Science, the Journal of Biological Chemistry, the Journal of Clinical Investigation, the Journal Experimental Medicine) from 1979 to 1983. Of the 25,000 articles searched, about 500 (2%) contained some potential claim to future applicability in humans, about 100 (0.4%) resulted in a clinical trial, and, according to the authors, only 1 (0.004%) led to the development of a clinically useful class of drugs (angiotensin-converting enzyme inhibitors) in the 30 years following their publication of the basic science finding. They also found that the presence of industrial support increased the likelihood of translating a basic finding into a clinical trial by eightfold.

Still, regardless of the study's limitations, and even if the authors were to underestimate the frequency of successful translation into clinical use by 10-fold, their findings strongly suggest that, as most observers suspected, the transfer rate of basic research into clinical use is very low. [7]

An editorial in Nature in 2010:

The readers of Nature should be an optimistic bunch. Every week we publish encouraging dispatches from the continuing war against disease and ill health. Genetic pathways are unravelled, promising drug targets are identified and sickly animal models are brought back to rude health. Yet the number of human diseases that can be efficiently treated remains low — a concerning impotency given the looming health burden of the developed world's ageing population. The uncomfortable truth is that scientists and clinicians have been unable to convert basic biology advances into therapies or resolve why these conversion attempts so often don't succeed. Together, these failures are hampering clinical research at a time when it should be expanding. [8]

Rothwell stated in the Lancet in 2006:

Indeed, most major therapeutic developments over the past few decades have been due to simple clinical innovation coupled with advances in physics and engineering rather than to laboratory-based medical research. The clinical benefits of advances in surgery, for example, such as joint replacement, cataract removal, endoscopic treatment of gastrointestinal or urological disease, endovascular interventions (eg, coronary and peripheral angioplasty/stenting or coiling of cerebral aneurysms), minimally invasive surgery, and stereotactic neurosurgery, to name but a few, have been incalculable. Yet only a fraction of non-industry research funding has been targeted at such clinical innovation. How much more might otherwise have been achieved? [9]

Sharon Begley, writing in the Wall Street Journal:

“Patients," says immunologist Ralph Steinman of Rockefeller University, New York, "have been too patient with basic research.“…Many of the brightest scientists have, therefore, plunged into the minutiae of roundworm genes and fruit-fly receptors, instead of human diseases. "Most of our best people work in lab animals, not people," says Dr. Steinman, who presents his case in a recent issue of the journal Cerebrum. "But this has not resulted in cures or even significantly helped most patients.”… “Human experiments are much more time-consuming and more difficult than animal studies," says Rockefeller's James Krueger, whose human research includes trying to correlate gene activity and changes in immune-system cells with the progression of psoriasis. "There are also funding issues. It's much easier to write a successful grant proposal for animal experiments. Animals are homogeneous, and let you say 'aha!' in a neat, clean experiment.” Humans, in contrast, are genetically and behaviorally diverse, making it hard to tell whether some aspect of their disease reflects the disease alone, their DNA, how they live -- or some messy permutation of all three. [10]

Zerhouni was quoted in the June 25, 2012 issue of Forbes as saying: “R&D in pharma has been isolating itself for 20 years, thinking that animal models would be enough and highly predictive, and I think I want to just bring back the discipline of outstanding translational science, which means understand the disease in humans before I even touch a patient.” [11] (Emphasis added.) Note that Zerhouni now seems more in agreement with the scientists quoted above. This agreement arguably reaches its zenith in the following. Zerhouni was quoted in NIH Record in 2013:

“We have moved away from studying human disease in humans,” he lamented. “We all drank the Kool-Aid on that one, me included.” With the ability to knock in or knock out any gene in a mouse—which “can’t sue us,” Zerhouni quipped—researchers have over-relied on animal data. “The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem…We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.” [12]

Today, the vivisection activist website Speaking for Research published a retraction or clarification of the above from Zerhouni. The “clarification” took the form of a letter, dated 2013, to Frankie Trull of the Foundation for Biomedical Research (FBR), another vivisection activist organization, although older and better funded than Speaking of Research. Zerhouni’s letter to FBR was in response to a letter (and doubtlessly other communication) to Zerhouni asking about his comments quoted above. Zerhouni replied, in part:

I understand that some have interpreted these comments to mean that I think that animals are no longer necessary in medical research. This is certainly not what I meant. In fact, animal models and other surrogates of human disease are necessary — but not sufficient — for the successful development of new treatments. In short, animal models remain essential to the basic research that seeks to understand the complexities of disease mechanism. [13]

I would now like to compare this situation with a similar one in 1992.

In 1984, Albert Sabin, one of the inventors of the polio vaccine, stated under oath to the US Congress:

Paralytic polio could be dealt with only by preventing the irreversible destruction of the large number of motor nerve cells, and the work on prevention was long delayed by the erroneous conception of the nature of the human disease based on misleading experimental models of the disease in monkeys. [14]

Ender, Weller, and Robbins grew the virus in tissue culture and this allowed the vaccine to be developed. For this achievement, not experiments on monkeys, Ender, Weller, and Robbins were awarded the Nobel Prize in Physiology or Medicine in 1954. The Prize was not awarded to Sabin or Salk or any other animal modelers who had worked with monkeys. The vaccine could have been produced from non-animal tissue, however manufacturers opted for monkey kidney tissue instead. Thus even monkey tissue cannot be held as necessary for the vaccine.

In any event, animal activists seized upon Sabin’s comments as proof that monkeys did more harm than good in developing the polio vaccine (a position that I agree with). Sabin came under immense pressure from vivisection activists and had a letter published on March 20, 1992 in the Winston-Salem Journal  [15] where he said animal experiments were vital to the development of the polio vaccine. Several things are significant about this.

1. This was not the New York Times or Washington Post, papers that are consider papers of record for the US. If a man of Sabin’s stature was going to retract a statement that he had given under oath before the US Congress, I assume a more prominent newspaper would have given him the space to do so. Or, he could have sent a retraction to Congress.

2. I really don’t think we can consider this retraction valid as it contradicts a previous statement under oath. Many people say one thing under oath and another when not under oath. Which does society usually believe?

3. Finally, when Sabin testified he was alone speaking his mind. When he wrote the letter he was aligned with vivisection activist groups such as Americans for Medical Progress, so again I ask which statement should society believe?

Note the parallels to the Zerhouni situation. A letter to Ms Trull, who represents the vivisection industry as a whole, is not on the same level as a statement made at NIH and in front of NIH researchers. An adage in politics goes something like this: “What do you call an unrehearsed statement made at an unguarded moment that the person’s aids later attempt to clarify? The truth.” Zerhouni on two occasions spoke the truth in statements that did not need clarification. Only after taking flack from vested interest groups for speaking the truth was a “clarification” needed.

Moreover, in Zerhouni’s case, his statements take place in an environment of scientists and the scientific community as a whole that agrees with his notion that animal models are of no predictive value. (For more examples, see There is consensus on prediction and Is the use of sentient animals in basic research justifiable?) Animals are used as predictive models and the use of animals in all areas of science and research is justified to society on the basis of the success of using animals as predictive models in drug development and disease research (which is performed in large part so drugs can be developed to treat the disease).

One cannot say that such models are part of the problem and then say at a later date that the very same way animal models were being referred to previously are in fact necessary. The drug targets that fail a very large percentage of the time in clinical trials were discovered in so-called basic research involving animal models. Hence the lack of efficacy that the pharmaceutical industry is complaining about. Finally, we have a record of Zerhouni’s statements where he appears to be changing from the historical party line regarding animal models to a more current, science-based acceptance of the limits of animal models.

Society is therefore forced to ask whether Zerhouni’s original comments should be taken at face value given that they were obviously not coerced? Or should society accept as truth Zerhouni’s letter to a person representing a rather large vested interest group and that changes the meaning of Zerhouni’s comment to something essentially directly opposite of what he initially stated.

I have no idea what Zerhouni was thinking when he made those statements and neither does anyone else. Furthermore, given the essentially complete reversal of his position as stated in his letter, I do not trust anything he now says on the subject just as I do not trust politicians who say one thing to the crowd at a speech but then state the opposite when they communicate with the vested interest groups.

This is the world in which we live!

(Photo from Wikipedia Commons


1.         Munro, N. Congress wants payoff from increased NIH funding. 2003 November 3, 2003 December 26, 2009]; Available from:

2.         Philips, H., The Insider - Focus on Neuroscience. Brainstorming. . New Scientist, 2004. 184(2469): p. 54.

3.         Zerhouni, E.A., Translational and clinical science--time for a new vision. N Engl J Med, 2005. 353(15): p. 1621-3.

4.         Mullane, K. and M. Williams, Translational semantics and infrastructure: another search for the emperor's new clothes? Drug Discovery Today, 2012. 17(9-10): p. 459-68.

5.         Contopoulos-Ioannidis, D.G., E. Ntzani, and J.P. Ioannidis, Translation of highly promising basic science research into clinical applications. Am J Med, 2003. 114(6): p. 477-84.

6.         Anonymous, Lost in clinical translation. Nat Med, 2004. 10(9): p. 879.

7.         Crowley, W.F., Jr., Translation of basic research into useful treatments: how often does it occur? Am J Med, 2003. 114(6): p. 503-5.

8.         Editorial, Hope in translation. Nature, 2010. 467(7315): p. 499.

9.         Rothwell, P.M., Funding for practice-oriented clinical research. Lancet, 2006. 368(9532): p. 262-6.

10.       Author, Physician-Researchers Needed To Get Cures Out of Rat's Cage. Wall Street Journal, 2003.

11.       Herper, M. Can Bush's NIH Chief Fix The Drug Industry? 2012 May 6, 2012 [cited 2013 July 31]; Available from:

12.       McManus, R. Ex-Director Zerhouni Surveys Value of NIH Research. 2013 June 21, 2013 [cited 2013 July 19]; Available from:

13.       Zerhouni, E. Letter to Trull. 2013 February 19, 2014 [cited 2014 February 19]; Available from:

14.       Sabin, A., Testimony before the subcommittee on Hospitals and Health Care, Committee on Veterans Affair’s, House of Representatives, April 26, 1984 serial no. 98-48, 1984.

15.       Sabin, A, The Correct Conclusion. Winston-Salem Journal, 1992. March 20.