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Beyond Animal Research
By Jarrod Bailey, Ph.D.
Nonhuman Primates in Medical Research: Sensible or Dispensable?
Amid growing tension and controversy over animal research, and experimentation involving nonhuman primates (NHPs) in particular, one salient point is avoided by all but a small number of people working hard to address it: Does it actually work? Has using NHPs in experiments made a positive contribution to human medical progress?
A Hazard to Human Health
Every area of research in which NHPs have been used provides evidence against its utility1:
- AIDS: With rare exceptions, NHPs don’t develop AIDS when infected with HIV; experimental results cannot be confidently extrapolated to humans.2-5 None of 50-plus NHP-tested vaccines (such as “Aidsvax”) has succeeded in humans.6 Effective anti-HIV drugs were conceived and developed using in vitro and in silico methods, without reliance on animal models.7-8
- Hepatitis (HCV): NHP experiments have failed to contribute to elucidate HCV infection, vaccine development, and understanding hepatocellular damage,9 with most progress relying on in vitro and clinical studies. Significant differences exist in viral infection and disease between humans and NHPs.10-12
- Alzheimer's disease: NHP models have failed to inform us of Alzheimer’s disease pathology.13,14 Plaques and tangles in the brain are the hallmark of Alzheimer's disease in humans, but not in monkeys.14 Human and in vitro studies produced the important genetic, biochemical, and lifestyle information and hypotheses that are elucidating the disease. An Alzheimer’s “vaccine”—AN-1792—was well-tolerated in monkeys,15,16 but caused strokes and inflammation of the central nervous system in humans.17
- Parkinson’s disease: Fundamental differences in the symptoms and pathology of Parkinson’s disease exist between NHPs and humans.18 Major breakthroughs arose through epidemiology, clinical studies, genetic research, human tissue studies, and autopsies.
- Stroke: NHPs have artificially modeled strokes for decades, despite critical physiological differences. Significant species and strain-specific differences exist.19 Of about 150 drugs found to be successful in animals (often NHPs), none has been successful in humans.20-22
- Hormone replacement therapy: This therapy was found to be protective against heart disease and stroke in NHPs, but actually increased the risk in humans.23
NHP experiments confound medical research because of fundamental genetic and biochemical differences between humans and NHPs:
- Humangenes confer greater susceptibility to age-related neurodegenerative diseases such as Alzheimer's and Parkinson's.24
- In chimpanzees, 20 out of 333 genes implicated in human cancer are different;25 560 genes show differences that can affect the immune system;26 169 genes in the cerebral cortex are expressed differently;27 and in the prefrontal cortex, 965 genes are expressed in humans but not chimps, and 344 in chimps but not humans.28 Of genes commonly expressed in the two species, 20 percent have a different expression profile, of which 52 genes are linked to neurological diseases.28
- Eighty percent of proteins are different to some degree in chimpanzees compared with humans.29
Work is underway to scientifically assess the postulated benefits of NHP research, including that of chimpanzees, and to determine the degree to which the above differences affect its validity.
What Else Can We Do?
Ending NHP research would benefit human medicine by halting the flow of unreliable data from it, and by diverting research funds to more appropriate and promising methods. These include batteries of human-based tests that provide reliable and relevant information on which to base further research and translate laboratory findings to the clinic: microarrays and other DNA technologies; proteomics and metabolomics; mathematical and computer modelling; epidemiology; human clinical research; myriad in vitro molecular biological techniques; microfluidics devices; scanning technologies, microdosing etc.... in short, technologies that have demonstrably contributed to human medicine.
While we persist with futile NHP models and keep better technologies “on the fringe,” millions of people are waiting for science to deliver. If the scientific establishment doesn’t face up to reality, they’ll be waiting for a while longer yet.
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2. Kaufman SR et al. (1996) In: Shortcomings of AIDS-Related Animal Experimentation. Medical Research Modernization Committee, New York. Available: http://www.mrmcmed.org/aids.html. Accessed 2006 Aug 23.
3. Anzai T et al. (2003) Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions / deletions as the major path to genomic divergence. Proc Natl Acad Sci USA. 100:7708-7713.
4. Koopman G et al. (1999) The relative resistance of HIV type 1-infected chimpanzees to AIDS correlates with the maintenance of follicular architecture and the absence of infiltration by CD8 cytotoxic T lymphocytes. AIDS Res Hum Retroviruses. 15:365-373.
5. Nath BM et al. (2000) The chimpanzee and other non-human-primate models in HIV-1 vaccine research. Trends Microbiol. 8:426-431.
6. Wilson C (2003) HIV vaccine hopes still high. New Scientist. 2385:7.
7. DeVita VT Jr. et al. (1992) AIDS Etiology, Diagnosis, Treatment, and Prevention, 3rd ed. JB Lippincott, Philadelphia, USA.
8. Vacca JP et al. (1994) L-735,524: an orally bioavailable human immunodeficiency virus type1 protease inhibitor. Proc Natl Acad Sci USA. 91:4096-4011.
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12. Lanford RE et al. (2001) The chimpanzee model of hepatitis C virus infections. ILAR J. 42:117-126.
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14. St. George-Hyslop PH and Westaway DA (1999) Alzheimer’s disease. Antibody clears senile plaques. Nature. 400:116-117.
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16. Young E (2002) Alzheimer’s vaccine trial suspended. New Scientist Jan 22.
17. Steinberg D (2002) Companies halt first Alzheimer vaccine trial. The Scientist. 16:22.
18. Hantraye P (1998) Modeling dopamine system dysfunction in experimental animals. Nuclear Med Biol. 25:721-728.
19. Huang J et al. (2000) A modified transorbital baboon model of reperfused stroke. Stroke. 31:3054-3063.
20. Neff S (1989) Clinical relevance of stroke models. Stroke. 20:699-701.
21. Wiebers DO et al. (1990) Animal models of stroke: are they relevant to human disease? Stroke. 21:1-3.
22. Wiebers DO et al. (1990). Prospective comparison of a cohort with asymptomatic carotid bruit and a population-based cohort without carotid bruit. Stroke. 21:984-988.
23. Gray S (2003) Breast cancer and hormone-replacement therapy: The Million Women Study. Lancet. 362:1332.
24. Emory University Health Sciences Center press release, 2003 Oct 13.
25. Puente XS et al. (2006) Comparative analysis of cancer genes in the human and chimpanzee genomes. BMC Genomics. 7(1):15.
26. Puente XS et al. (2005) Comparative genomic analysis of human and chimpanzee proteases. Genomics. 86(6):638-647.
27. Caceres M et al. (2003) Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci USA. 100(22):13030-13035.
28. Marvanova M et al. (2003) Microarray analysis of nonhuman primates: validation of experimental models in neurological disorders. FASEB J. 17(8):929-931.
29. Glazko G et al. (2005) Eighty percent of proteins are different between humans and chimpanzees. Gene. 346:215-219.