Biomedical Engineering Reference
In-Depth Information
the broader context of their geographical distributions and
population structure, which have influenced their suitability
as animal models for particular diseases, and the extent to
which most recent genetic studies substantiate that
taxonomy. As significant controversy exists regarding
taxonomy and insufficient genetic studies have been
completed to verify taxonomy based on morphological
criteria, controversies are discussed without providing
a definitive taxonomy in this chapter.
However, species more distantly related to humans than
chimpanzees are susceptible to most human diseases and
serve as more practical and economical animal models.
Consequently, the Cercopithecoid superfamily of Old
World monkeys, native to Africa and Asia, whose common
ancestor diverged from the ancesters of Hominoidea as late
as 23 mya (
Raaum et al., 2005
) or as early as 34.5 mya
(
Steiper et al., 2004
), are the animal models of choice. New
World monkeys of the family Cebinae have also been
employed as animal models. While their relationship to
humans is more remote than that of cercopithecoids, they
provide the models of choice for certain, especially
nonviral, infectious diseases.
BIOMEDICALLY RELEVANT PRIMATE
SPECIES
Chimpanzees
Chimpanzees, from whom humans diverged 5
Old World Monkeys
Cercopithecoid primates, or Old World monkeys, share
approximately 93% of their genome with humans (
Gibbs
et al., 2007
) and are relatively morphologically homoge-
neous because they diverged rapidly and relatively recently.
Consequently, their phylogenetic relationships are difficult
to resolve, and, while they are well studied, considerable
disagreement over their proper taxonomic classification
persists, with anywhere between 10 and 22 different genera
proposed for this superfamily of primates (
Disotell, 1996
).
They are divided into two families, Colobinae and Cerco-
pithecinae, each characterized by a synapomorphical trait
that documents their monophyletic taxonomic status:
a specialized digestive tract for eating leaves and buccal
pouches, respectively. This primary subdivision and the
species composition of each family are supported without
conflict by both morphological (
Groves, 2001
) and
molecular (
Xing et al., 2005
) data, and their divergence
from each other has been dated to approximately 16 mya
(
Raaum et al., 2005
).
No members of the colobine subfamily have been
widely used in biomedical research, but cercopithecine
primates are well-represented in biomedical research.
According to a 2009 US Fish and Wildlife Department
report, approximately 126 000 longtail macaques and
20 000 rhesus macaques were imported to the USA during
the period 2000
7 mya,
represent our closest living relative, with whom we share
nearly 99% of our genome, althought the conservatism of
taxonomy has resisted the formal recognition, well-
confirmed by molecular evidence, that we humans share
a monophyletic clade with chimpanzees to the exclusion of
all other primates. Chimpanzees' close genetic relationship
with humans renders them the only model for the study of
a few human diseases, such as those resulting from the
human immunodeficiency virus (HIV-1;
Nath et al., 2000
),
hepatitis B virus (HBV;
Rehermann and Nascimbeni,
2005
), and hepatitis C virus (HCV;
Bukh, 2004
) infection,
and the best model for others, such as testing of monoclonal
antibodies for treatment of cancer and autoimmune
diseases and evaluating the toxicity and pharmacokinetic
properties of drugs. However, both ethical and financial
issues preclude the widespread use of chimpanzees as
animal models in biomedical research, and most countries
have discontinued their use for this purpose. Chimpanzees
are presently housed at several US facilities, including the
Alamogordo Primate Facility at Hollomen AFB in New
Mexico, the Southwest National Primate Research Center,
the Primate Foundation of Arizona, the New Iberia
Research Center in Louisianna, the Michale E. Keeling
Center for Comparative Medicine and Research of the
University of Texas M.D. Anderson Cancer Center in
Bastrop, and the Yerkes National Primate Research Center
near Atlanta.
Chimpanzees that have been employed in previous
research, many of which were experimentally infected with
pathogenic agents, are still used in the USA for behavioral
research and biomedical research for which they are the
sole sufficient model, but a moratorium exists on breeding
most of these animals (those owned or supported by the
NIH). Because fewer than 1000 chimpanzees now exist in
captivity, the US National Chimpanzee Resource
Committee (NCRC) has called for the end of this morato-
rium (
VandeBerg et al., 2005
).
e
2005 alone (
Pavlin et al., 2009
). Genetic
markers have been identified, such as the 12s rRNA of
mitochondrial DNA (mtDNA), that can distinguish species
and subspecies of cercopithecines (
van der Kuyl et al.,
2000
). The family Cercopithecinae contains two major
divisions (tribes), one whose involvement in biomedical
research is almost solely represented by vervet monkeys
(species of genus Chlorocebus) and another, papionins,
whose involvment in research has been much more exten-
sive. The papionins include two major taxa, one comprising
the species of genus Macaca and the other the baboons of
the genus Papio together with several other closely related
genera representing mandrils (Mandrillus sphinx), drills
e
