Opinion:  GVN – Chimpanzees in Biomedical Research

Franco Buonaguro, M.D
Director of Molecular Biology and Viral Oncology,
Italian National Cancer Institute, Naples,
Member of the Global Virus Network.

As presented in a recent GVN companion piece on September 18, 2013, federal rules are being implemented and proposed in the United States that would restrict the use of chimpanzees in biomedical research except under very stringent circumstances. While one rule is still in the proposal stage (the Department of the Interior is proposing to place all chimpanzees, whether wild or captive, on the Endangered Species List), the path forward for the National Institutes of Health (NIH) is finalized.  Implementation of the NIH’s plan to retire most of the research chimpanzees it owns or supports will significantly reduce the use of chimpanzees in biomedical research. While anti-vivisection groups, in particular the New England Anti-Vivisection Society (NEAVS), believe that NIH decision’s to keep a “reserve” population of up to 50 animals for “future potential research” is unscientific and unnecessary, other groups uphold that even 50 is not enough, that this ban on the use of chimpanzees will strongly limit advances on biomedical research. The issue is very controversial.  In general, the views fall between two extremes:

  Chimpanzee studies are unique and crucial for certain human illnesses. Proponents of this stance argue that chimpanzee research is essential to reducing risks for human research subjects for certain diseases, and remains necessary for discovery of treatments and cures.  Paradigmatic of this perspective is the view expressed by John VandeBerg and Stuart Zola in a 2005 Commentary piece in Nature, “A unique biomedical resource at risk.”

Biomedical research with chimpanzees is unethical. Those on the anti-vivisection side do not accept the necessity of – or, at least the ethical basis for – biomedical research in chimpanzees.  Jarrod Bailey, although a member of NEAVS, seems to be quite objective and unbiased in his 2010 evaluation published in Alternatives to Laboratory Animals (ALTA).

  As is often the case, the truth is in the middle.  Great Apes (including chimpanzees) represent the animal model closest to humans, and when other animal models are not available, although chimps are very expensive, the scientific community will tend to use them as proof of concept, in order to speed discovery and development.  Here are some examples:

Human immunodeficiency virus (HIV).  In the 1980s and into the early 1990s, several colleagues from major primate centers conducted studies in chimps, animals that, like humans, could be infected with HIV field isolates.  Marc Girard (who headed the French research agency’s HIV Vaccine Task Force from 1988-1998 and was also the Director General of the Mérieux Foundation in Lyon from 2001-2003) was one of the few to have the opportunity to perform such studies in Europe.  Major disappointment in HIV vaccinology resulted from the human negative results with recombinant gp120 in comparison to the previous positive/protective results obtained in chimps.  I would say that in the last ten years, very few studies (if any) related to HIV research have been conducted in chimpanzees, and this 2008 article in ALTA by Bailey is quite a fair assessment of the role of chimpanzees in HIV/AIDS research.

 Hepatitis C virus (HCV).  Until recently, chimps have played a major role in HCV research.  For years, only chimpanzee-based models were available for study, with no in vitro replication systems available until just a few years ago.  As recently as 2001, Lanford et al. concluded, “The chimpanzee will continue to provide a critical aspect to the understanding of HCV disease and the development of therapeutic modalities.”  The work of these scientists has been very relevant in defining the effective role of anti-miRNA 122 molecules in treatment of chronic HCV infection, confirmed also in human clinical trials.  Moreover, considerations on the subsequent activation of several oncogenes (see them described in the RNAi Therapeutics blog) clearly illustrate the need for pre-clinical animal models to address specific questions.  In general, however, at the moment, given the availability of in vitro as well as ex vivo models, chimpanzee studies are probably less relevant for HCV research.  Again, Bailey has addressed the issue quite fairly.

Ebola virus.  The use of chimpanzees to study the Ebola virus raises entirely different questions of utility.  As very well described at the May GVN meeting in Munich, the Ebola virus infects different species of fruit bat: the hammer-headed or big-lipped fruit bat (Hypsignathus monstrosus), Franquet’s epauletted fruit bat (Epomops franqueti), and the little collared bat (Myonycteris torquata).  The infection is asymptomatic in bats, but very dangerous in humans as well as in non-human primates, including chimps.  These primates are dying in their wild habitat, and any work to develop a vaccine for human use may be just as relevant for use in wild primates.  These types of studies should have a major priority to save our non-human “cousins” and to develop an effective preventive strategy for high-risk populations, as in Congo and Northern Uganda.  An outbreak of Ebola hit Kampala as recently as November 2012.  The availability of fast and intercontinental air transportation increases the risk of transmission of such infections in communities worldwide.

 

In conclusion, taking into account the relevance of biomedical advances, ethical issues, as well as costs, studies in non-human primates should be performed following criteria conventionally used for humans, particularly when relevant for the chimpanzees’ own health with respect to disease prevention and treatment.  It could be extremely hazardous to swing from an uncontrolled use of these animals to an overprotective attitude, which could hamper advances toward their health as well as ours.