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Beyond Animal Research
By Jarrod Bailey, Ph.D.
September 2006 |
Non-Human Primates in Medical Research: Sensible or Dispensable?
Amid growing tension and controversy over animal research, and
experimentation involving non-human 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
Differences Matter
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.
References
1. Bailey J (2005) Non-human primates in medical
research and drug development: a critical review. Biogenic
Amines 19(4-6): 235-255.
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.
9. Rosen HR and Martin P (2000) Hepatitis B
and C in the liver transplant recipient. Seminars
Liver Dis 20: 465-480.
10. Zanetti AR et al. (1995) Mother-to-infant
transmission of hepatitis C virus. Lombardy Study
Group on Vertical HCV Transmission. Lancet 345:
289-291.
11. Major ME and Feinstone SM (2000) Characteristics
of hepatitis C infectious clones in chimpanzees. Curr
Topics Microbiol Immunol 242: 279-298.
12. Lanford RE et al. (2001) The chimpanzee
model of hepatitis C virus infections. ILAR
J 42: 117-126.
13. Guela C et al. (1998) Aging
renders the brain vulnerable to amyloid β-protein
neurotoxicity. Nat Med 4: 827-831.
14. St. George-Hyslop PH and
Westaway DA (1999) Alzheimer’s disease. Antibody
clears senile plaques. Nature 400: 116-117.
15. Sibal LR and Samson KJ (2001) Nonhuman primates:
A critical role in current disease research. ILAR
J 42: 74-84.
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.
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