LETTER TO THE EDITOR: Regarding Bettauer 2010 (39:9–23)
D. Rick Lee DVM 1, Stuart M. Zola PhD 2, John L. VandeBerg PhD 3, Thomas J. Rowell DVM 4, Christian Abee DVM 5
Journal of Medical Primatology
Early View (Articles online in advance of print)
Article first published online: 18 AUG 2010
DOI: 10.1111/j.1600-0684.2010.00437.x
Author Information
1 Washington National Primate Research Center, Seattle, WA, USA
2 Yerkes National Primate Research Center, Atlanta, GA, USA
3 Southwest National Primate Research Center, San Antonio, TX, USA
4 New Iberia Research Center, New Iberia, LA, USA
5 Center for Comparative Medicine and Research, Bastrop, TX, USA
Publication History
Article first published online: 18 AUG 2010
The Journal of Medical Primatology recently published a paper entitled ‘Chimpanzees in hepatitis C virus research: 1998–2007’ by R.H. Bettauer (2010, 39:9–23). This paper concluded that there is no ‘sufficient data, or scientific consensus,... [for] the biological relevance of’ the use of chimpanzees as a model for hepatitis C virus (HCV) research. In addition, this article claimed that because chimpanzee studies ‘have not produced a reliable... vaccine’, the chimpanzee model should be abandoned. We, the National Chimpanzee Resource Consortium, have major concerns regarding the validity of this article, and we consider it to be inappropriate for publication in a scientific journal.
It appears that this study was initiated and supported by The Humane Society of the United States (HSUS), an organization that openly advocates an ‘end to the use of animals in biomedical research’ [1]. As stated by the author, the purpose of this article ‘was to ascertain the extent of chimpanzee use... and any related health and welfare issues.’ It is our view that this article does not objectively evaluate the effectiveness of the chimpanzee model in hepatitis C research. The article appears to contain numerous unsubstantiated conclusions that support the HSUS agenda of banning the use of chimpanzees in biomedical research.
It is our position that the chimpanzee is the only scientifically validated model for in vivo studies of hepatitis C infection [2], and it is essential for the evaluation of antiviral and vaccine efficacy, as well as safety. Research with chimpanzees over many years was critical to the development of the hepatitis B vaccine (licensed in 1982) and the hepatitis A vaccine (licensed in 1992). We consider the argument that the chimpanzee model for hepatitis C research should be abandoned because a hepatitis C vaccine has not yet been developed is as absurd as the same argument regarding hepatitis A and B would have been in 1980. It took 47 years to develop the polio vaccine. Hepatitis C virus was discovered in 1989, only 21 years ago, and great progress has been made in developing an understanding of HCV biology and virus–host interactions from research with chimpanzees, as we move toward developing an effective vaccine.
The author argues that because HCV infections were not found in wild chimpanzees, ‘humans and chimpanzees may respond to HCV exposure differently.’ However, HCV is transmitted almost exclusively by transfusion (prior to testing the blood supply) and intravenous injection with contaminated needles. Not finding HCV in wild chimpanzees has nothing to do with response to exposure, as the animals are never exposed. Very few animal models mimic the human disease exactly.
The author states that ‘small study sizes [in HCV research] lack statistical power and therefore affect our ability to draw broader conclusions.’ Many citations refute that conclusion. For example, in one study two chimpanzees were infected with HIV and infused 60 minutes later with a monoclonal antibody that blocks the HIV receptor on CD34 cells [3]. The chimpanzees did not become infected, although the single control animal did become infected. The monoclonal antibody has since been humanized and is expected to enter clinical trials this year. The results speak for themselves. Therefore, no statistical analyses were needed.
The author states that ‘studies that involve human patients...included large numbers of subjects, which avoids the problem of small sample sizes found in chimpanzees studies.’ The implied conclusion seems to be that we should use humans instead of chimpanzees. However, the kinds of experiments that can be conducted with chimpanzees cannot be conducted with human subjects (e.g., the HIV experiment mentioned earlier).
The author states that ‘there is currently not sufficient data or scientific consensus to establish the biological relevance of the chimpanzee model for HCV.’ As evidence that is contrary to the author’s statement, we refer the readers to the recent publication in Science of results from chimpanzees that establish great promise for a microRNA-silencing drug (SPC3649) for treating hepatitis C patients [4].
The author makes several references to the ‘lack of information on anesthesia and analgesia’ in the articles she surveyed. The implication appears to be that studies upon chimpanzees are carried out without regard to anesthesia and/or analgesia. Initiation of any research study with chimpanzees requires that the study be approved by an Institutional Animal Care and Use Committee and that the study conform to guidelines set forth by the Animal Welfare Act (as amended) and the Guide for the Care and Use of Laboratory Animals [5, 6]. These regulations require the use of anesthesia and analgesia, and the implication that HCV studies were conducted with chimpanzees were without anesthesia and analgesia is in our view unwarranted.
We are concerned that the Journal of Medical Primatology, a reputable scientific journal whose mission is to disseminate knowledge regarding primates as models to study, prevent, and/or treat human diseases, has published this article as we contend that it lacks objectivity critical to research work and is influenced by the animal rights lobby.
Respectfully submitted by the National Chimpanzee Resource Consortium
References
1 The Humane Society of the United States. [Internet]. Recent hepatitis C study challenges chimpanzee use. Press Release December 15, 2009. Available at: http://www.humanesociety.org/news/press_releases/2009/12/hepatitis_c_research_using_chimps_121509.html
Accessed date: 02/05/10.
2 Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M: Pathogenesis of hepatitis C virus infection in Tupaia belangeri. J Virol 2010; 84:303–311.
3 Wang CY, Sawyer LS, Murthy KK, Fang X, Walfield AM, Ye J, Wang JJ, Chen PD, Li ML, Salas MT, Shen M, Gauduin MC, Boyle RW, Koup RA, Montefiori DC, Mascola JR, Koff WC, Hanson CV: Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex. Proc Natl Acad Sci USA 1999; 96:10367–10372.
4 Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Ørum H: Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010; 327:198–201.
5 Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals. Washington (DC): National Academies Press, 1996.
6 United States Department of Agriculture: Animal Welfare Act as Amended. 7 USC §2131–2156, 2007.
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