Commentaries, Health March 7, 2016

Why Chimpanzee-Testing in Medicine Had to End

by Jonathan Latham

by John J. Pippin, M.D., F.A.C.C.
A French man died last month and five others in the same clinical trial were hospitalized after they took an experimental drug. The drug had been deemed safe for humans after having been tested on chimpanzees in preclinical trials.

The National Institutes of Health’s recent decision to end federally supported chimpanzee experimentation could prevent future fatalities like this by promoting more human-relevant research methods.

Twenty of those government-owned chimpanzees currently housed at a testing laboratory in San Antonio, Texas, are next in line to be transferred to a sanctuary. As the use of chimpanzees in medical experiments draws to a close, it’s important to examine the superior, nonanimal research methods that will benefit patients.

Tracy at Chimp Haven
Tracy at Chimp Haven

In 2011, I was invited—as a cardiologist, medical educator, and former animal researcher—to testify before the Institute of Medicine Committee panel that ultimately determined that use of chimpanzees is not essential for any area of disease research.

I told them that there was a better way. That when we were told that the use of chimpanzees had been and would be important for HIV vaccine development, we should remember that three decades of vaccine research using chimpanzees and other nonhuman primates has been startlingly unproductive. This eventually led the National Institutes of Health to cease funding for HIV-AIDS research using chimpanzees.

Scientists now recognize the critical role of humans who are naturally resistant to the effects of HIV—so-called elite controllers and long-term non-progressors. These patients, some of whom have lived with HIV, but without treatment and without illness, for as long as three decades, produce broad and potent neutralizing antibodies. These prevent HIV from entering cells and replicating, and induce HIV to mutate into less pathogenic forms.

Some naturally resistant persons have been exposed hundreds of times to HIV without becoming infected. Researcher Michel Nussenzweig from The Rockefeller University in New York described his purpose in studying these individuals

“[H]ere’s a way of copying what exists in nature and that we know can work because of the long-term survivors. Instead of inventing something that doesn’t exist, it’s trying to copy something that does exist.”

I also urged the committee that when we were told that chimpanzees were essential for the study of the hepatitis C virus (HCV) and the development of an HCV vaccine, we should consider that, just as for the hepatitis A and B viruses, there are numerous validated methods to study HCV and to develop vaccines, without using chimpanzees.

Longitudinal studies of human HCV patients, such as the Johns Hopkins long-term study of HCV-infected intravenous drug users, provide human-specific information regarding many aspects of HCV acquisition, natural history, therapeutic responses, and vaccine opportunities. In combination with the numerous human-based cell culture systems, this provides a robust research methodology that is more reliable. It makes chimpanzee experiments redundant.

Chimpanzees were also proposed to study human Alzheimer’s disease and other neurological disorders. While both humans and chimpanzees may develop brain amyloid plaques, the protein structures of those plaques are different. And though these plaques are thought to be either a cause or a consequence of Alzheimer’s in humans, they are inconsequential for chimpanzees, in whom Alzheimer’s does not occur. In fact, cross-species genetic studies have documented that gene expression in the chimpanzee cerebral cortex has “no detectable similarity” with that detected in humans.

Much of the best information regarding Alzheimer’s and other neurological diseases derives from longitudinal studies of patients and post-mortem brain studies. Numerous advanced neuroimaging methods are available that can replace chimpanzee experiments with more human-specific results. These same imaging methods are used extensively in the study of many human psychiatric disorders. When combined with longitudinal studies of patients, these can replace chimpanzee experiments, again with human-specific data.

In a 2005 review of animal experimental models in neuropsychiatry, UK researchers stated clearly what others in the field have confirmed:

“[M]odelling human mental disorders in experimental animals is fraught with difficulties. Depression models generally lack both clinical and scientific credibility and have, thus far, failed to inform treatment strategies previously acquired through serendipity.”

The authors further state:

“As one enters the ‘real world’, it becomes apparent that it is almost impossible to control not only the variables manipulated in the lab, but also the variables that cannot be modelled in animals—cognition, emotion, social behaviour, relationships, etc.”

These examples of the failed paradigm of chimpanzee experiments are not only characteristic but immutable. Why? Because despite sharing all but a few percent of our genes with chimpanzees, there are still tens of millions of DNA sequence differences plus innumerable and variable differences in gene expression between our two species.

The Institute of Medicine agreed with me and other experts calling for an end to chimpanzee experiments. Its decision—and the recent NIH decision—make it clear that there is no necessity or compelling scientific justification for the use of chimpanzees to study human diseases and treatments and that turning from animal experiments to modern methods would represent genuine progress.

Dr. Pippin is a Dallas physician and reformed animal researcher who testified in support of ending chimpanzee research before the Institute of Medicine in May 2011.

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Comments 9
  • Why use chimpanzees for medical experiments when there are better methods? Our government should fund ONLY human-relevant research!

  • It is so great to read this. Using another species to study ourselves is such an absurd idea. We are worlds apart from even our closest relatives!

  • This restriction has long seemed like a good thing. But why aren’t other species on the list….raising rather deep ethical and practical problems? If even chimps aren’t so good a model for humans why are monkeys used? Much more cogent may be asking about the millions of mice and rats subjected to what they are routinely subjected to? And what about other mammals, or why do even our current problematic ethics stop at mammals? The ethical issues also include biomedical practices that allow testing–essentially, experiments–on humans in countries with more lax restrictions than in the US or Europe.

    It is true that we don’t yet have good cell culture methods to solve these problems and inference from humans is limited for similar ethical reasons. The issues meld with those about meat-eating and how domestic animals are cared for, or not. Clearly we evolved as omnivores, so we face perplexing dilemmas. So limiting the exercise of powers we have over other species is going to be an ongoing issue about which there are strong feelings.

    But we can be thankful that the chimps are now being sent to nice retirement communities to live out their days in peace.

  • Dr. Pippin raises some excellent points. In my observation, animal research has always been more about dollars than sense. When the majority of “identical” human twins who were raised together develop different diseases, how in the world can we believe that disease progression in a primate or a rat or a mouse can predict disease progression in a human… or that a treatment that eradicates illness in a non-human animal will translate to an effective treatment for us? What is left unstated in the title to this article is that ALL animal testing has to end. It is a failed paradigm, supported only by those who profit from if.

  • It’s like Zika. Most people who test positve for Zika never know they have it. Isn’t that how the ideal vaccine works? Shouldn’t the best way to tackle the alleged Zika problem be to study all the people who are asymptomatic…and figure out why? Is there a co-factor to that–in most cases–highly effective natural inoculation by mosquito that prompts some people to suffer illness? Poor nutrition? Exposure to toxins?

    Can scientists demonstrate any degree of common sense…before whole areas are drowned in pesticides, which will have their own consequences?

  • charities and, the historical failure of animal research, visit. facebook.com/garyfair96 (no lie can live forever!).

  • An interesting article with some valid points. However, one striking error must be corrected. The authors writes, “In fact, cross-species genetic studies have documented that gene expression in the chimpanzee cerebral cortex has “no detectable similarity” with that detected in humans.” This is simply not correct as a stark unqualified statement. For example, there will be many hundreds of shared genes which are expressed in the cerebral cortex of both chimpanzees and humans. Perhaps the author meant that there is no detectable similarity in the *changes* in gene expression in response to amyloid plaque build-up, which would certainly help to support his argument.

    • Mark Featherstone, thanks for your comment.

      Gene expression differences for humans and chimpanzees are present at baseline and increase greatly with age. These results were not related to cognitive or pathological disease states. And while humans and chimpanzees indeed share genes that are expressed in the cerebral cortex, the patterns of expression do not correlate to a significant degree. Just one example from Fraser HB (2005) PLoS Biol 3(9): e274 [http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0030274]:

      “Using the 841 genes that change expression with age in human frontal pole [7], we tested the agreement between the aging-related changes in frontal pole and the changes in each of our three chimpanzee brain regions. As can be seen in Figure 4B, none of the three regions showed any significant correlations with human frontal pole (|r| 0.4 for all three). Similar results were found when comparing chimpanzee aging changes in any brain region to the patterns from either of our other two human expression datasets [19,20] for either the 841 genes or all aging-informative genes on the microarray (not shown). Therefore, we conclude that chimpanzee cortex has a reproducible pattern of aging-associated gene expression changes, but this pattern is completely different from that of human cortex.”

      Fraser concludes: “The fact that even the chimpanzee, our closest living relative, has patterns of age-related gene expression changes almost entirely different than human implies that making specific inferences about human brain aging from model organisms may be difficult.”

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