Biomedical Engineering Reference
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a rhesus monkey, by researchers at Oregon's Health and
Science University (OHSU) and the Oregon NPRC (
Chan
et al., 2001
). This work demonstrated the feasibility of
producing transgenic nonhuman primate human disease
models and was a major accomplishment in advancing gene
and cell therapy research. Next, another OHSU/Oregon
NPRC research team successfully derived embryonic stem
cells by reprogramming genetic material taken from skin
cells of an adult rhesus monkey (
Byrne et al., 2007
).
Almost simultaneously, a related report that probably got
even wider attention came from research at the University
of Wisconsin in which stem cells had been derived by the
reprogramming of human skin cells (
Yu et al., 2007
). The
team's leader, Dr James Thomson, headed the stem cell
resource at the Wisconsin NPRC and much of the research
was based on his pioneering work in that area done in
nonhuman primates in 1995 (
Thomson et al., 1995
). Both
projects showed the feasibility of producing pluripotent
stem cells from somatic cells in primates and thus promised
an attractive alternative to using embryos for generating
patient-matched stem cells. Yet again in 2009, the research
team in Oregon, building on its earlier research, reported
successfully replacing genes in primates (
Tachibana et al.,
2009
). The rhesus monkey twins, Mito and Tracker, were
the world's first primates to be produced by chromosome
transfer between eggs, an accomplishment seen as readily
translatable into human therapies for genetic disorders
mediated by mitochondrial DNA mutations (
Figure 1.10
).
Following up later on production of the first transgenic
monkey, a team at the Yerkes NPRC and Emory University,
part of whom were involved with the effort in Oregon in
2001, went on to produce the first transgenic nonhuman
primate model of a human disease (
Yang et al., 2009
). They
reported developing a transgenic model of Huntington's
disease in rhesus monkeys that, unlike transgenic mouse
models, had close physiological, neurological, and genetic
similarities to the human disease.
Shoukhrat Mitalipov, the leader of the team in Oregon
that produced Mito and Tracker, noted that their chromo-
some transfer technique had not yet been performed even in
mice and that, while he had learned much from work with
mice earlier in his career, “they were not primates.” He said
that only using nonhuman primates in this kind of research
would provide the essential bridge for bringing gene
therapy to human medicine (S. Mitalipov, personal
communication, 2010). These research accomplishments
provided proof in nonhuman primates of Francis Collins'
claim that “the genomics era is now a reality” (
Collins
et al., 2003
). The importance of using nonhuman primates
in genomic research was well understood by Collins, who
headed the Human Genome Project and the NIH's National
Human Genome Research Institute when both the chim-
panzee and the rhesus monkey genomes were sequenced
and who later became the director of the NIH itself
(
Collins, 2008
). This work gave meaning to a new term in
the medical sciences, translational medicine, that described
the inclusive process of bringing the drugs and medical
devices based on basic medical research to the direct help
of patients in the clinical setting.
Infectious Disease
Ebola virus and nonhuman primates again made the news
in 2010, but this time it was good news. A team primarily
involving researchers at Boston University's School of
Medicine and the US Army's Research Institute of Infec-
tious Diseases at Fort Detrick, Maryland, were able to show
that rhesus monkeys inoculated with lethal Ebola virus
could be completely protected by post-exposure treatment
with a novel RNA-based form of therapy that interfered
with the function of viral RNA (
Geisbert et al., 2010
). The
authors noted that the strategy might be useful not only for
treating people infected with Ebola virus but also as treat-
ment for other emerging viral infections. They noted as
well that, while rodent models were useful for screening
prospective treatments for Ebola, they are frequently not as
useful for predicting efficacy as nonhuman primate models.
Growth in the Use of Nonhuman Primates
General
The use of nonhuman primates following 2000 went
beyond simply continuing to be an important part of
biomedical research and testing; it also grew. As a review of
the subject had pointed out in the mid-1990s (
Bowden
and Johnson-Delaney, 1996
), despite the serious challenges
of harassment by animal rights advocates, increasingly
stringent
FIGURE 1.10
Tracker and Mito, rhesus monkey twins, taken at the
Oregon NPRC in 2009. They were the world's first primates to be
produced with the transfer of mitochondrial DNA, a landmark accom-
plishment in gene therapy research. (Photo courtesy of the Oregon Health
and Sciences University.)
regulatory requirements and research review
