University of Michigan Wk 6 Animal Research Critical Thought Essay

American Journal of Primatology 63:225?237 (2004)
RESEARCH ARTICLE
Use of Primates in Research: A Global Overview
HANS-ERIK CARLSSON1*, STEVEN J. SCHAPIRO2, IDLE FARAH1, and JANN HAU1
1
Department of Neuroscience, Division of Comparative Medicine, Uppsala University,
Uppsala, Sweden
2
Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center,
Bastrop, Texas
We assessed the use of nonhuman primates and nonhuman primate
biological material in research by reviewing studies published in 2001 in
peer-reviewed journals. The number and species of primates used, the
origin of the animals, the type of study, the area of research of the
investigation, and the location at which the research was performed were
tabulated. Additionally, factors related to the animals that may have
affected the outcome of the experiments were recorded. A total of 2,937
articles involving 4,411 studies that employed nonhuman primates or
nonhuman primate biological material were identified and analyzed.
More than 41,000 animals were represented in the studies published in
2001. In the 14% of studies for which re-use could be determined, 69%
involved animals that had been used in previous experiments. Published
studies most commonly used nonhuman primates or nonhuman primate
biological material from the species Chlorocebus aethiops (19%), Macaca
mulatta (18%), M. fascicularis (9%), and Papio spp. (6%). Of these
studies, 54% were classified as in vitro studies, 14% as noninvasive, 30%
as chronic, and 1% were considered acute. Nonhuman primates were
primarily used in research areas in which they appear to be the most
appropriate models for humans. The most common areas of research
were microbiology (including HIV/AIDS (26%)), neuroscience (19%), and
biochemistry/chemistry (12%). Most (84%) of the primate research
published in 2001 was conducted in North America, Europe, and Japan.
The animals and conditions under which they were housed and used were
rarely described. Although it is estimated that nonhuman primates
account for an extremely small fraction of all animals used in research,
their special status makes it important to report the many husbandry and
environmental factors that influence the research results generated. This
Contract grant sponsor: Swedish Board for Laboratory Animals (CFN); Contract grant sponsor:
Helge Ax:ons Jonsons stiftelse; Contract grant sponsor: Magn. Bergwalls stiftelse; Contract grant
sponsor: C.F. Lundstro?ms stiftelse.
n
Correspondence to: Dr. Hans-Erik Carlsson, Division of Comparative Medicine, Department of
Neuroscience, BMC Box 572, Uppsala University, SE-751 23 Uppsala, Sweden.
E-mail: [email protected]
Received 7 December 2003; revised 27 May 2004; revision accepted 9 June 2004
DOI 10.1002/ajp.20054
Published online in Wiley InterScience (www.interscience.wiley.com).
r
2004 Wiley-Liss, Inc.
226 / Carlsson et al.
analysis has identified that editors rarely require authors to provide
comprehensive information concerning the subjects (e.g., their origin),
treatment conditions, and experimental procedures utilized in the studies
they publish. The present analysis addresses the use of primates for
research, including the effects of a shortage of suitable nonhuman
primate subjects in many research areas. Am. J. Primatol. 63:225?237,
r 2004 Wiley-Liss, Inc.
2004.
Key words: nonhuman primates; research use; animal models
INTRODUCTION
Nonhuman primates constitute irreplaceable animal models for research
areas in which their close evolutionary relationship to humans ensures highfidelity models with predictive and discriminative abilities that may not be
available in other species [Bontrop, 2001; Goodman & Check, 2002; Hau et al.,
2000; Kaup, 2002; King et al., 1988; Sibal & Samson, 2001]. However, research
that relies on nonhuman primates is becoming increasingly difficult to sustain in
many countries. The supply of animals is not sufficient to meet current demands
[Cohen, 2000; National Research Council, 2003], and opponents of the use of
primates in research have become politically influential in recent years [Goodman
& Check, 2002].
By virtue of their taxonomic status and sentience, combined with their
relatively slow reproduction in captivity, primates present ethical and practical
challenges as animal models. Unlike most other species used in research,
primates typically have a long lifespan, often spend years in captivity, and are
frequently re-used in several independent studies during the course of their lives
[Boccia et al., 1995; van Vlissingen, 1997]. A well-defined, self-sustaining supply
of primates for scientific uses has been sought for many years [Editorial, 1976;
Kingston, 1994; National Research Council, 2003; Prescott, 2002; Smith, 1975],
but still remains elusive. Although considerable progress has been made toward
establishing self-sustaining nonhuman primate research resources [Schapiro
et al., 1994], the production of certain primate models has not been able to keep
pace with research demand [Cohen, 2000; National Research Council, 2003].
In view of the increasing debate on animal experimentation, and particularly
restrictions on primate research [Balls, 2000], it is important to present a
reasonably accurate overview of the current pattern of primate use for research.
There are a few reports available that list the species or research areas in which
nonhuman primates are used. Most of these reports are restricted to certain
geographical areas or individual species [Erwin, 1981; Fridman & Popova, 1983,
1988; Hampson et al., 1990; Zucker & Stacks, 1996]. The present analysis
presents an overview of the global use of primates and nonhuman primate
biological materials in all research published during a single year (2001).
It is well recognized that physiological factors related to the animals, the
physical environment, and the social environment affect the validity of the results
of a study [O?brink & Rehbinder, 2000]. A limited number of cross-sectional
surveys have examined the ??specifications?? of the laboratory animals and the
experimental conditions reported in the scientific literature [Boisvert, 1997;
Clough, 1982; Granados-Zuniga, 1997; Lang & Vessel, 1976; Smith et al., 1997].
The present study attempts to provide a systematic analysis of the conditions
under which primates have been used in scientific investigations.
Survey of Primate Use / 227
The aim of this study was to explore the use of primates and nonhuman
primate biological materials in research, as reflected by the scientific articles
published in 2001 that involved the use of such materials. Specifically, we were
interested in delineating the characteristics of the animals used and the research
that was conducted, and whether factors with a potential influence on
experimental outcome and/or animal welfare were reported.
MATERIALS AND METHODS
Data Collection
The present study is a retrospective literature survey of all identifiable peerreviewed, original articles that used some type of ??primate biological material??
and were published in 2001. We searched the Medline database (http://
www.ncbi.nlm.nih.gov/entrez/query.fcgi) for both common and generic names,
using all levels up to level five of the Taxonomy Browser. Additionally, we
performed a search using the following key words: monkey(s), ape(s), primate(s),
and vero [Rhim et al., 1969]. We also searched PrimateLit (http://primatelit.
library.wisc.edu/), a database that focuses specifically on publications involving
nonhuman primates, to identify any articles that were not included in Medline.
Only those articles published in scientific journals that according to ISI Journal
Citation Reportss had an impact factor for the year 2000 were included in the
analysis. A total of 2,937 primate articles involving 4,411 studies that were
published in 699 different journals from a variety of disciplines within the fields
of biological, behavioral, physiological, laboratory, and/or medical sciences were
identified and examined.
Description of the Analysis
Each of the 4,411 studies included in the present investigation was analyzed
for information concerning the animals, the topic areas of the study, housing and
husbandry practices, and factors of importance to the outcome of the research.
Information recorded about the animals included the source of supply, species,
gender, age, weight, number of animals, experimental status, and geographic
location of the experiment. Topic areas for the studies were selected to most
accurately describe the research hypotheses addressed by the investigation. The
conditions of housing and husbandry that were registered included cage size,
animal density, ambient temperature, relative humidity, lighting, ventilation,
cleaning, enrichment, exercise, and feeding and watering schedules. Factors of
importance for the outcome of the research noted were the severity of the
procedure, conditioning, duration of the experiment, anesthesia, euthanasia, and
experimental endpoint. The number of animals used per study was only
considered for analysis when a specific total number of subjects was clearly
stated or could be easily calculated from the Materials and Methods section of the
article. We were usually able to obtain data for the recorded factors by reading the
Materials and Methods section of the study. In some cases, we had to consult
additional sections of the article in order to determine the values for one or more
of the factors.
Definitions of Terms Used
For the current analysis, the primate studies examined were classified into
four types of studies: acute, chronic, noninvasive, and in vitro. A study was
228 / Carlsson et al.
classified as acute if the animal was used once, with the experimental procedures
performed under nonrecovery anesthesia. A study was classified as chronic if the
animal was conscious during or after an invasive procedure. Any experiment that
required more than a single injection was considered to be invasive. A study was
classified as noninvasive if no invasive procedures (i.e., no injection) were
performed on the animal. A study was classified as in vitro if the investigation was
performed on materials (e.g., tissue cultures or preserved tissue) that originated
from animals euthanized before the study.
An article was considered to involve more than one study if more than one
species was used and/or more than one of the four experimental categories were
represented. Many studies contained a component that could be considered
molecular or cellular biology, but if this was not the primary focus of the article,
the studies were not classified as such.
RESULTS
More than 41,000 nonhuman primates were studied in the 35% of the 2,937
articles published in 2001 in which the number of subjects was explicitly reported
or could be calculated from the Materials and Methods section. Old World
monkeys predominated (64.7%), followed by New World monkeys (15.5%) and
apes (8.9%) (see Table I). Of the remaining studies, 2.5% were performed on
species that were not identified, 1.7% involved lesser apes, 0.4% used tarsiers, and
6.3% involved prosimians. Chlorocebus aethiops (19%), Macaca mulatta (18.4%),
M. fascicularis (8.6%), Papio spp. (5.9%), and Pan spp. (4.9%) were the most
common taxonomic groups. Old World monkeys were the most commonly used
superfamily, except in studies conducted in South America, in which New World
monkeys were used in 482% of the studies.
Approximately two-thirds of all studies using primates or primate material
were categorized as either in vitro (54%) or noninvasive (14%). Of the 54% of
studies classified as in vitro, 50% were performed on cultured cells or on samples
from preserved museum specimens. Therefore, approximately one-half of the
studies analyzed actually used only primate ??biological materials?? (wellestablished cell lines) as their ??subjects,?? rather than whole, living primates.
This is an important point to consider when one examines issues related to
primate useFespecially for C. aethiops, a species in which established cell lines
are used far more frequently than live animals. In the remaining in vitro studies
(4%), the animals were euthanized to obtain raw material for the experiment.
Chronic and acute studies accounted for 31% and o1%, respectively, of the
44,400 studies analyzed.
The origin of the experimental animals was specified in 37% of the articles
(see Table II). In this subset of the sample, 54% used captive-born subjects, 27% of
the studies were performed on primates in the wild, 5% used wild-caught animals,
and 14% used primates for which the source was specified, but not the breeding
conditions.
In 14.4% of the articles, it was explicitly stated whether the subjects had
served, or would serve, in multiple experiments. In these studies, the majority
(69%) of primates were ??re-used?? (see Table II). In studies in which animals were
euthanized to obtain raw materials for in vitro experiments, 86% of the animals
had been used in previous experiments. In chronic experiments, more than 63% of
the animals had been subjected to an earlier procedure. In acute and noninvasive
studies, 75% and 72%, respectively, of the animals had been used before.
Survey of Primate Use / 229
TABLE I. Nonhuman Primate Species Appearing in Scientific Journal Articles in 2001,
N=4,301, Frequency and Percentages*
In vitro
Hominidae (Apes)
Gorilla spp.
Pan spp.
Pongo spp.
Hylobatidae (lesser apes)
Cercopithecidae (Old World monkeys)
Cerocebus spp.
Cercopithecus spp.
Chlorocebus aethiops
Macaca spp.
M. mulatta
M. fascicularis
M. fuscata
M. nemestrina
M. radiata
Other Macaca
Unspecified Macaca
Papio spp.
Other Cercopethicidae
Platyrrhini (New World monkeys)
Callitrichidae spp.
Saguinus spp.
Alouatta spp.
Aotinae spp.
Atelinae spp.
Callicebinae spp.
Cebinae spp.
Other Platyrrini
Strepsirhini (prosimians)
Cheirogaleidae spp.
Galagonidae spp.
Lemuridae spp.
Other Strepsirhini
Tarsiidae
Unspecified primate
Total
Other studies
Sum
Total
382
65
112
59
54
27
98
21
21
92
210
80
2,783
33
64
817
1,470
793
369
19
26
764
14
38
53
110
50
8
15
6
26
9
78
64
683
319
85
61
24
44
40
176
81
60
52
17
39
27
61
35
95
56
16
27
28
6
103
25
155
108
33
28
59
33
164
29
40
74
36
1
85
2,111
24
10
26
33
15
21
2,190
53
50
100
69
75
64.7
%
8.9
2.1
4.9
1.9
1.7
19.0
18.4
8.6
254
145
5.9
667
15.5
3.6
2.5
55
3.8
272
6.3
16
106
4,301
0.4
2.5
100
*
Studies (n=110) performed on material from extinct species were excluded.
The most common areas of research (see Table III) in the articles examined
were microbiology (including HIV/AIDS, 26%), neuroscience (19%), biochemistry
(12%), and pharmacology/physiology (11%). The frequency with which particular
species were used was dependent on the area of research. For example, C. aethiops
(primarily cell lines) was most frequently used in microbiology, M. mulatta was
most commonly used in neuroscience, and Pan spp. was preferred for genetics.
Fifty percent of all primate research was conducted in North America, 24%
was conducted in Europe, and 10% was performed in Japan (see Table IV).
Studies related to behavior, conservation, and ecology were conducted more
frequently in geographic locations with a significant primate fauna than in
230 / Carlsson et al.
TABLE II. Percentage of Studies That Specified Experimental Factors by Study Type*
Source of supply
Experimental statusb
Nai?vec
Reusedc
Conditioningb
Duration of experiment
Anesthesia stated
Euthanasia stated
Euthanasia method
Determined endpoint
Number of animalsd
Medianc
Averagec
SDc
Acute
Noninvasive
Chronic
In vitroa
Overall
24.3
10.8
1
3
n.a.
29.7
100
100
81.1
n.a.
85.4
5
7.1
6.2
63.1
13.1
23
60
14.4
52.7
n.a.
n.a.
n.a.
n.a.
49.5
10
50.5
218.2
27.6
14.2
72
120
15.2
74.8
54.2
24.6
76.3
9.6
86.5
7
15.4
37.4
19.0
21.0
6
38
n.a.
n.a.
n.a.
100
57.7
n.a.
78.6
5
16.3
44.9
37.0
14.4
*
n=2242.
Only animals euthanized for this purpose.
Wild animals were excluded from experimental status and conditioning.
c
Values in table represent numerical values, not percentages.
d
In 20 studies, a range of animals was given instead of a fixed number. Therefore, calculations were based on the
average of the range given. All but one of these studies were noninvasive.
a
b
TABLE III. The Most Frequently Used Nonhuman Primate Species and the Research Areas
Where Primates Are Most Commonly Used (Number of Studies)*
Micr Neur Bioc
C. aethiops
354
M. mulatta
102
M. fascicularis
38
Papio spp.
30
Pan spp.
25
Cebinae spp.
14
Callitrichidae
16
spp.
Lemuridae spp.
3
Saguinus spp.
10
M. fuscata
2
Gorilla spp.
5
Total
599
Gene Cons
Endo
Cons Phar HIV Phar HIV Etho Surg Phys Total
31
251
132
17
11
33
38
240
36
26
19
3
4
10
33
27
11
35
63
19
16
24
13
6
23
44
40
26
46
76
51
13
5
22
9
47
106
16
8
13
0
2
14
35
13
13
36
13
17
4
35
36
44
4
8
1
18
46
18
23
3
0
10
36
39
12
16
0
2
5
847
766
359
241
207
155
150
4
8
37
4
566
0
1
6
0
345
54
10
4
43
315
33
47
9
22
287
1
1
2
2
228
1
0
2
2
197
10
19
16
7
193
0
3
5
3
143
2
1
2
0
123
0
1
5
0
116
108
101
90
88
3,112
*
n=3112.
Micr, microbiology; HIV, HIV/AIDS; Neur, neuroscience; Etho, ethology; Bioc, biochemistry; Surg, surgery/
anatomy; Gene, genetics; Endo, endocrinology/reproduction; Cons, conservation/ecology/anthropology; Phys,
physiology; Phar, pharmacology.
countries with no primate fauna. Of the chronic studies, 59% were conducted in
North America, 22% were performed in Europe, and 7% were conducted in Japan.
In vitro studies were conducted primarily in North America (46%), Europe (33%),
and Japan (8%). Twenty-eight percent of the noninvasive studies were conducted
in Japan, 21% in Africa, 18% in North America, and 14% in Europe. In Europe
and Japan, approximately equal numbers of M. mulatta and M. fascicularis were
Survey of Primate Use / 231
TABLE IV. Number of Articles Arranged According to Research Area and the Geographic
Location Where the Study Was Performed, Frequency and Percentage, N=2931*
Microbiology
Neuroscience
Biochemistry
Pharmacology
Conservation/
Ecology/
Anthropology
Genetics
Ethology
HIV/AIDS
Endocrinology/
reproduction
Physiology
Surgery, anatomy
Other
Total
%
Africa
Asia
Japan
13
1
1
7
35
7
17
10
50
70
49
13
74
42
6
8
7
1
2
7
2
129
4.4
Austr.
S. Am
N. Am
Europe
Total
%
11
8
7
3
23
8
8
6
263
325
180
130
181
136
87
42
576
555
349
211
19.7
18.9
11.9
7.2
10
0
38
24
16
204
7.0
17
2
5
13
36
11
3
0
1
9
12
1
84
79
116
61
52
36
193
189
177
6.6
6.4
6.0
15
6
0
7
163
5.6
9
10
5
18
294
10.0
3
4
1
3
44
4.0
1
3
1
6
116
1.5
81
57
59
73
1,471
50.2
24
24
29
26
714
24.4
134
106
102
135
2,931
4.6
3.6
3.5
4.6
100
100
*
Six articles that used biological material from more than one continent were excluded.
used. In North America and Asian countries (except Japan), M. mulatta was used
three times more frequently than M. fascicularis. Most studies involving apes
were conducted in North America (42%), Europe (28%), and Japan (12%).
In general, many of the factors related to the animals (e.g., gender, age, and
weight) and their environment were infrequently specified in the published
articles (see Table V). In more than 50% of the articles analyzed, none of these
parameters were described. In the following section, we discuss the role of
institutional animal care and use committees as a potential influence on why such
parameters are infrequently reported. The gender, age, and weight of the subjects
were the most frequently explicitly described characteristics, except for
noninvasive experiments, in which weight was specified in only 6% of the studies.
The size of the cage and the number of animals per cage were relatively
frequently specified in noninvasive studies, but in chronic studies only the
population density was occasionally described. Information concerning food
and water availability was only included with any frequency in chronic and
noninvasive studies.
Table V lists the findings regarding a number of experimental factors.
Information concerning the severity of a procedure, anesthesia, euthanasia,
experiment duration, and number of primates used per study were frequently
reported. When the UK Home Office guidelines were used to score procedural
severity, 19% of the studies were scored as mild, 74% were moderate, and only 7%
were of substantial severity. M. mulatta, M. fascicularis, and Papio spp. were the
most frequently used species in studies of substantial severity (79%). Experiments of substantial severity were most common in AIDS research (26%), surgery
(16%), and microbiology (11%). Using the median as a measure of the typical
study sample size, we found moderate sample sizes (five to 10 animals) in all types
of experiments. The length of the quarantine period was specified in 9.6% of the
studies in which wild-caught primates were used in captivity, and 9.8% of the
232 / Carlsson et al.
TABLE V. Percentage of Studies That Specified Factors Related to the Animals, Housing, and
Husbandry by Study Type, N=2018*
Gender
Age
Weight
Housingb
Cage size
Animal density
Ambient temperature
Relative humidity
Lighting
Ventilation
Cage cleaning
Enrichment
Exercise routines
Feeding type
Nutrient composition
Feeding schedule
Watering schedule
Acute
Noninvasive
Chronic
In vitroa
Overall
45.9
29.7
37.8
5.4
0
8.1
5.4
5.4
5.4
0
0
0
0
0
0
2.7
2.7
43.3
22.3
6.0
28.4
16.0
29.8
2.5
2.3
4.8
0.3
0.5
6.0
0
22.1
6.5
18.4
16.0
50.1
23.7
32.6
17.9
2.8
20.6
8.5
6.7
11.2
1.9
0.6
2.4
0.5
19.3
10.0
18.7
18.1
38.1
24.8
14.8
4.3
0.5
3.8
2.9
2.4
2.4
0
0
0.5
0
3.8
1.9
0.5
2.9
47.3
23.8
25.1
18.3
5.5
20.5
6.6
5.3
8.9
1.3
0.5
2.9
0.4
17.9
8.2
16.7
15.7
*
Studies using wild primates were excluded.
Only animals euthanised for this purpose.
Primates living outdoor were excluded from specification of factors related to indoor housing.
a
b
studies in which primates were transferred from a supply unit to the location of
the laboratory. Studies related to pharmacology, physiology, endocrinology, or
behavior were the most likely to specify experimental factors.
DISCUSSION
The need for animals in biomedical research is well recognized by society
[Hagelin et al., 1999]. However, the moral acceptability of this use has been
debated for centuries. This is particularly true for the use of nonhuman primates.
There is significant opposition to the use of primates for research in many parts of
the world, particularly in certain countries in the European Union (EU) and
Japan [Pifer et al., 1994]. There have even been calls for a complete ban on the
use of primates for research in Europe [Balls, 2000]. However, the importance of
using primates for biomedical research has been emphasized by the scientific
community [Hau et al., 2000] and the EU [Scientific Steering Committee, 2002].
For some applications in biomedical research, primate models are indispensable
because of their phylogenetic similarity to humans [Hau et al., 2000].
The present study of more than 2,900 articles that used primates and/or
biological materials from primates, and were published during 2001 in 699 peerreviewed journals clearly elucidates the great diversity of primate research.
Although we aimed to provide an accurate estimate of the number of nonhuman
primates used for research, the current data suggest that this is not possible. Only
37% of the articles specified how many animals were used in the studies.
Additionally, not all research that uses primates is designed for publication, and
not all research designed for publication actually gets published. In fact, the
report of the UK Animal Procedures Committee states that 72% of all research
Survey of Primate Use / 233
primates in the UK are being used in regulatory toxicology studies that were not
designed for publication [GB Home Office, 2002].
Although the data compiled in this study provide some indication of the
number of primates used in research, it is difficult to generate an accurate
estimate of such a number because 1) some primates are used in multiple
experiments, 2) some are used only for breeding purposes, and 3) not all research
that involves primates is designed for publication [Bowden & Johnson-Delaney,
1996]. Although there are published population surveys of primates covering
individual countries [e.g., Crook, 1991] or species [e.g., Stephens, 1995], and one
survey of captive primates in Europe and North Africa is available [Wilde et al.,
1994], there are no published data addressing the number of primates used for
scientific purposes, even when the focus is only on those held in captivity. The
present analysis may provide a reasonable starting point for generating a
functional estimate of primate use.
Our best estimate of the number of nonhuman primates used in research,
including those participating in several protocols, would therefore be 100,000?
200,000 animals annually. Of these, we estimate that 1,000?2,000 animals have
been terminated in acute and in vitro studies. We were unable to determine
whether the 30,000?60,000 nai?ve primates introduced into research annually
replace those that have been euthanized or retired. Compared to the number of
mice and rats used in research (estimated, based on European statistics, to
constitute roughly 100 million annually), nonhuman primates would represent
considerably less than 1/10 of 1% of the animals used in research.
A wide variety of primate species were used in the studies reported,
representing members of all four superfamilies. A fraction of the studies
examined (2.5%, most of which involved in vitro experiments) did not specify
the species of primate used. Although 56 different extant species or subspecies
were clearly identified as subjects, this may be an underestimate since some
studies only described the family of the primate used. The proportions of studies
utilizing apes, Old World monkeys, New World monkeys, and prosimians in 2001
do not appear to differ significantly from those reported for the past two decades
by Zucker and Stacks [1996]. Two species (C. aethiops and M. mulatta) accounted
for 37% of all studies. However, most of the studies involving C. aethiops material
included in vitro procedures performed on commercial tissue culture cells.
M. fascicularis, Papio spp., and Pan spp. complete the list of the top five most
frequently used species (see Table III), and just 11 species accounted for 72% of all
studies. Macaca was the most frequently used taxonomic group, in accordance
with previous reports [Fridman & Popova, 1983; Bowden & Smith, 1992; Weber,
1997; Prescott, 2002].
Of the most frequently used primates, C. aethiops was used almost
exclusively as a source of commercially obtained kidney cells (Rhim et al., 1969)
for biochemistry and virology investigations. M. mulatta was primarily used in
neuroscience and AIDS research, and M. fascicularis was used mainly in
neuroscience. Papio spp. subjects were most commonly used in surgery and
genetics research, and Pan spp. and Gorilla spp. were mostly used in studies of
genetics and conservation.
Primates are basically undomesticated animals, and the issue as to what
constitutes the most appropriate source of primates for use in research has been
debated within the scientific community and among animal activists and
regulatory authorities. The use of wild-caught primates has been criticized, and
is prohibited in some countries, including the UK [GB Home Office, 1998].
Primates for research are produced in captivity in a variety of different settings,
234 / Carlsson et al.
including free-ranging colonies on islands (using wild-caught breeders), and caged
colonies (using captive-bred breeders) [National Research Council, 2003].
Assuming that the proportion of animals of different origins is representative
in the 37% of articles that specified the source of supply, the majority (54%) of the
animals studied were captive-born. About 5% were wild-caught, and approximately 14% came from other sources. This latter group included animals from
free-ranging colonies, unspecified ??captive-born?? animals, unspecified ??purposebred?? animals, unspecified ??zoo?? animals, imported animals not further
specifying source, and unspecified wild-caught animals. About 27% of the studies
were performed on free-ranging primates. The origin of the animal was specified
most frequently for noninvasive studies (63%), less frequently for acute or chronic
studies (25%), and even less frequently for in vitro studies (19%).
Information concerning subject re-use was provided in 14% of the articles
analyzed. Approximately 25% of the animals used in acute or noninvasive studies,
50% of those used in chronic studies, and 14% of animals euthanized to obtain
raw materials for in vitro studies were experimentally nai?ve. This indicates that
about two-thirds of all primates represented in the analyzed studies were re-used.
It is reasonable to assume that surviving animals were or will be used in other
protocols (those published in 2001 as well as those published in previous and
subsequent years).
There is a critical shortage [Cohen, 2000; National Research Council, 2003] of
captive-bred nonhuman primates for use in research in general, and for AIDS
research in particular (for which M. mulatta of Indian origin is the present model
of choice). This may be a contributing reason for the frequent re-use of primates
in multiple procedures and/or investigations. Other reasons include financial
imperatives and the ethical unacceptability of euthanizing primates that have
been used in noninvasive or mildly invasive procedures from which they recover
fully. This is the case in the United States, where euthanasia of chimpanzees is
allowed only to alleviate suffering [National Research Council, 1997]. If primates
are re-used, they must not suffer as a result of previous experiments, and the data
from new studies must not be compromised by previous protocols. If this is the
case, we consider re-use an appropriate technique for managing and utilizing
a resource that is both exceptionally valuable and in exceptionally short supply.
In some cases, the use of wild-caught animals may be justified, particularly for
species that are not endangered and are considered pests, and thus are subject to
government culling programs. Instead of being simply eradicated, these primates
are now occasionally being used for research in source countries [National
Research Council, 2003].
The present inadequate production of captive-bred primates in the United
States and Europe necessitates importations from source countries in Asia,
Africa, and South America. Long distance transportation to North America,
Europe, and temperate regions in Asia is likely to induce considerable stress on
the relocated animals. The change to a temperate climate, new patterns in the
light/dark cycle, and a different diet may forever change the constitution of an
animal. For animal welfare reasons, as well as scientific and financial reasons, it is
important to develop primate research centers in source countries [National
Research Council, 2003].
In the present study, we found that research utilizing nonhuman primates
was most most frequently conducted in the disciplines of microbiology (including
HIV/AIDS), neuroscience, and biochemistry. Pharmacology/physiology, anthropology/conservation, genetics, and behavior also accounted for substantial
proportions of primate use, as they have in recent decades [Erwin, 1981; Fridman
Survey of Primate Use / 235
& Popova, 1983; Zucker & Stacks, 1996]. Comparisons of our data with previous
findings suggest that studies of genetics and HIV/AIDS are among the fastestgrowing areas of research that use nonhuman primates and/or their biological
materials.
A substantial proportion (84%) of all primate studies were conducted in
industrialized countries. Chronic and in vitro studies were most common in
North America and Europe, while noninvasive studies were relatively more
prominent in Afri