Sunday, March 6, 2016

2237. Why Chimpanzee-Testing in Medicine Had to End

By John J. Pippin, Independent Science News, March 7, 2016

A chimpanzee at the National Institutes of Health in Chimp Haven in Louisiana. 
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.

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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