Biomedical Engineering Reference
In-Depth Information
followed afterwards when those countries moved towards
banning all exports of nonhuman primates.
Chimpanzees probably offer one of the best examples of
trends in the conservation of nonhuman primate use.
Beginning in 1975 with the advent of CITES, importation
of wild chimpanzees into the USA ceased for all practical
purposes. Their cost also soared. Many chimpanzees were
typically used in a succession of experiments in an NIH,
FDA, and CDC consortium established to conduct hepatitis
research. Many of these chimpanzees were experimentally
infected and became chronically infected with hepatitis B
virus. They were considered unsuitable for breeding or
other research purposes. By 1980, research usage was not
a limiting factor in the longevity of chimpanzees. Very few
animals died of research-associated mortality. In fact, the
provision of appropriate housing and care for older chim-
panzees that had outlived their usefulness in research began
to pose a serious problem.
that appeared to be associated with immunodeficiency
(
Henrickson et al., 1983
). According to Henrickson
(personal communication, 2010), the number of deaths
continued to grow to the point where one whole outdoor
breeding enclosure was lost. In a situation eerily reminis-
cent of the AIDS drama that was unfolding in San Fran-
cisco about the same time, the idea that an infectious agent
was involved was initially controversial among primate
veterinarians, many of whom felt the cases occurring in
California represented an isolated incident that could well
be due to other causes such as environmental toxins or
pollutants.
Observing that the disease in macaques had so many of
the characteristics of human AIDS, including cutaneous
fibrosarcoma and opportunistic infections, Jay Levy, a well
known AIDS researcher in San Francisco interested in the
cases at the center, was led to comment that they invited
comparison to the human cases he was seeing and might
offer a valuable model for studying that disease (J. A. Levy,
personal communication, 2010). It was not until similar
cases began to occur in macaques elsewhere across the
country and there was an increasing amount of information
about the cause of AIDS that attention began to shift
towards identifying an infectious agent for the immuno-
deficiency disease in macaques (
Letvin et al., 1983
) (see
section “Retroviral disease and simian immunodeficiency
virus (SIV)” below).
Retroviral Disease
Among the vast amount of knowledge about nonhuman
primates that was accumulated during this period were
developments, little noticed at the time, which would
significantly affect the future of using nonhuman primates
in biomedical research. In 1967, an outbreak of lymphoid
disease, including lymphomas, was reported in baboons at
the IEPT in Sukhumi (
Rabin, 1985
). The outbreak was
notable because neoplastic diseases in nonhuman primates
up to that point were unusual. The disease was trans-
missible with tissue passage and affected animals were
immunodeficient.
Between 1971 and 1973 spontaneous deaths from
lymphocytic and granulocytic leukemia were reported in
colonized gibbons at two separate locations, the University
of California at San Francisco and Walter Reed Army
Institute of Research's component at the SEATO laboratory
in Bangkok (
Johnsen et al., 1971; Kawakami et al., 1972;
De Paoli et al., 1973
). Type C retroviruses, designated as
two separate strains of Gibbon Ape Leukemia Viruses
(GALVSF and GALVSEATO), were implicated as causa-
tive agents and the disease could be transmitted by viral
inoculation (
Snyder et al., 1973; Kawakami and Buckley,
1974
).
In 1974, a type D retrovirus, named the Mason-Pfizer
Monkey Virus (MPMV), was isolated from a spontaneous
mammary adenocarcinoma in a colonized rhesus monkey
being used for pharmaceutical research; the virus was later
found to be widespread in normally appearing monkeys in
the colony as well (
Mumtaz et al., 1974
).
Almost coincidentally, veterinarians at the California
NPRC between 1969 and 1975 began to see an unusual
number of cases of lymphoma in their macaques. A little
later, they also began seeing an increasing number of cases
1980
S
AND 1990
S
: PROGRESS PAYING
OFF IN THE FACE OF SERIOUS
CHALLENGES
A Nobel Prize
In 1981, David Hubel and Thorsten Wiesel shared the
Nobel Prize in Physiology and Medicine for their studies of
how visual information is transmitted to and processed in
the visual cortex of the brain (
http://www.rockefeller.edu/
research/faculty
). They used both cats and macaques for
their work, with macaques being provided by the New
England NPRC. Their research had important human
clinical applications, an example of which was that
congenital cataracts in neonates, if not treated promptly,
could result in developmental failures in the visual cortex
and permanent blindness. Their work in a nonhuman
primate model provided convincing evidence of the bene-
fits that followed timely cataract removal in young children
in the clinical setting (
Wiesel and Hubel, 1974
).
Retroviral Disease and Simian
Immunodeficiency Virus (SIV)
In 1984, a type D retrovirus, later called SRV, was impli-
cated as a cause of the disease associated with the early
