Use of live nonhuman primates in research in Asia
Synalsvagen 10, SE 757 57 Uppsala, Sweden
Synalsvagen 10, SE 757 57 Uppsala
Background: Use of live non-human primates (NHPs) in biomedical research is a controversial issue in many parts of the world. Recent use of NHPs in research in Asian countries was surveyed.
Aim: To elucidate the use of NHPs in research in Asian countries.
Settings and design: The peer-reviewed literature was sampled according to the species used, area of research, research class and geographic location. Articles derived from database searches were scrutinised.
Methods and Material: Studies were identified from the PrimateLit database.
Results and Conclusion: Results suggested that NHP research was conducted in 16 countries, of which Japan accounted for two-thirds. About 55% of studies involved use of live animals, whereas the remaining 45% used some lower level of biological material. More than 70% of the studies using live NHPs included use of Old World monkeys. M. fuscata (18%), M. mulatta (17%) and M. fascicularis (10%) were the three most commonly used species. The most common research areas were neuroscience (44%), conservation (14%) and behaviour (11%). Due to high demand for NHPs, there is room for increased breeding of NHPs to be used for research in Asian countries.
|How to cite this article:|
Hagelin J. Use of live nonhuman primates in research in Asia
.J Postgrad Med 2004;50:253-256
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Hagelin J. Use of live nonhuman primates in research in Asia
. J Postgrad Med [serial online] 2004 [cited 2020 Mar 28 ];50:253-256
Available from: http://www.jpgmonline.com/text.asp?2004/50/4/253/13638
Nonhuman primates (NHPs) continue to be used as models for humans in many areas of biomedical research e.g. development, behaviour, neuroscience, and infectious diseases, throughout the world. There is no consensus among stakeholders worldwide about whether it is ethical or not to use live NHPs for invasive research protocols. Legislation in many countries and international guidelines are based on the 'Three R principle' (Reduction, Refinement, Replacement). This principle constitutes that provided NHPs are considered to be the most appropriate animal model for the characteristics under investigation, then the number of animals used should be minimised. Proponents to the use of live NHPs in research tend to emphasise that human subjects are not practical for the experimental approaches for ethical reasons, or that phylogenetically lower-ranking species are too dissimilar from humans in some of the characteristics under investigation. Further, because humans share many anatomical, physiological, behavioural and genetics characteristics with other primate species, NHPs will continue to serve a critical role in biomedical research. Live NHPs are also involved in other types of scientific applications, like anthropology, conservation, ecology and veterinary science.
NHPs constitute a factor in different parts of society in Asian countries: Efforts have been made to preserve species facing extinction, both in the wild and by establishment of rehabilitation centres, including eco-tourism. NHPs are regarded as a health hazard in cities and on the countryside where crop raiding is a problem. NHPs bred for experimental use are exported from a number of Asian countries to other parts of the world. China, Israel and Vietnam export M. mulatta, and China, Indonesia, Israel, the Philippines and Vietnam export M. fascicularis., India banned export of all NHPs to be used for research purposes in 1977. This ban has led to a demand for M. mulatta of Indian origin in other countries. There seems to be relatively high level of political opposition to the use of NHPs in research in India compared to other Asian countries., The results of surveys addressing opinions to the use of NHPs in research in Asian countries indicate that although many support this use, there is also a notable opposition in Indonesia and Japan., The use of live NHPs in research in Asia according to the species used, research area, research class and geographic location has not been studied before. The aim of the present paper was to analyse the use of NHPs in research that has recently been carried out in Asian countries and not to stress on the ethical issues concerning their use.
Materials and methods
The present study surveyed all original articles that could be identified from PrimateLit that used NHPs and were published in the year of 2001. Only journals indexed with Science Citation Index were included. Overall, 456 articles containing 651 studies published in 214 journals were scrutinised. A sub-sample (n=80) was subjected to parallel sampling. The outcome was similar.
An article was considered to contain more than a single study if more than one species was used and / or more than one of the four experimental classes mentioned below were employed. This may be illustrated by: if one animal was first subjected to some chronic procedure and then was euthanised and its cells and tissues were utilised, then it was classified as one chronic invasive study. If cells and tissues were obtained from another animal than the one used in the chronic study, then it was classified as two studies. Articles containing more than one species were counted on the basis of number of species used.
The geographic location where the project was undertaken was preferred to the address of the primary author.
Sampling was done according to the research area of the journal. For multidisciplinary journals the articles were scored according to where it fit best according to the headings employed in [Table:3].
Studies were grouped according to the experimental classes used in Hagelin:11 1) Chronic invasive study was characterised by the NHP being conscious during at least some part of the experiment. Procedures in studies categorised as chronic invasive may have varied from routine blood sampling to more invasive procedures in which the subjects may have suffered pain, distress and / or lasting harm. 2) Chronic non-invasive study implied that no physiological manipulation was performed on the NHPs. Some of these studies may have included psychological manipulations induced by the scientists, but not physiological, i.e. their body surface was not penetrated by any needle. 3) Cadaver study implied that subjects were euthanised by the authors or a professional in the same setting, prior to the actual experiment. These were almost exclusively animals that were euthanised for unrelated medical reasons or died of old age. 4) In vitro study implied that cells and / or tissues from NHPs were used. The biological materials for in vitro studies were often obtained from commercial companies or museums, but could also be body hair or faeces collected from cages or in the wild. Data derived from the GenBank was also included in this class.
The latter two experimental classes are generally not treated as animal experiments by legislation and guidelines.
Use of live or some lower level of biological material from NHPs for research in 16 Asian countries is shown in [Table:1]. The distribution of research classes seems to vary between individual countries. Since the focus of the present study was to elucidate the use of live subjects, studies classified as cadaver (5%) and in vitro (40%) were not taken into consideration for the rest of the results section. Among the use of live subjects in studies in [Table:2], the distribution was: Apes (10%), Lower apes (3%), Old World monkeys (71%), New World monkeys (13%), Prosimians (4%) and Tarsiers (1%). In total, 111 species were represented in these 358 studies (according to the classification of Groves). Macaca spp. were involved in 57% of all studies where live animals were used. Even though the sample was too small for statistically valid comparisons, the data indicate that species living in the wild in certain countries were more likely to be relatively more common in research in the same countries, i.e. M. radiata in India, Pongo spp. in Indonesia, and M. fuscata in Japan. About 44% of the studies were classified as neuroscience [Table:3]. All non-invasive studies classified as neuroscience in Japan, were related to eye research. In comparison, about 15% of the invasive neuroscience studies done in Japan were eye research. Studies related to virology and endocrinology were among the most frequent in China and India.
More than half of all studies identified involved the use of live NHPs [Table:1]. The majority of these studies were conducted in China, India, Indonesia and Japan. A comparison with Europe suggested that both the distribution of super families and general research areas conducted in Asia were rather similar in magnitude [Table:2] and [Table:3]. However, the proportion of non-invasive research was higher in Asia compared to Europe. The proportion of in vitro studies was lower in Asia compared to Europe. The main differences regarding research areas were that conservation, ecology and parasitology studies are rarely conducted in European settings, due to that there are very few free ranging NHPs in Europe. Macaca spp. has been the most common NHP species used in research for many years. M. fuscata (Japan) and M. radiata (India) seemed relatively more common in research in Asia than in Europe. Live apes in research were used in Japan, Indonesia and Malaysia [Table:2]. This is because only a few research centres have access to live apes to be used for research purposes in the region and that some of the studies were done in the species' natural habitat. In fact, worldwide live Pongo spp. is maximally used for research in Indonesia. Studies using live apes were almost exclusively non-invasive that were related to behaviour, conservation, and parasitology, apart from a few invasive ones related to genetics and virology. The distribution of research areas corresponds well with the use of live apes in other parts of the world.
Wild caught NHPs should not be used in biomedical research because they are subjected to stress of capture, and are of unknown age, health, and behavioural relationships. Bangladesh, Indonesia, Malaysia and the Philippines banned export of wild-caught NHPs in the mid 1990s. The use of captive NHPs is not curtailed by similar biological characteristics, which may be a negative factor in research protocols and increase variances. The process of international air-transport and re-housing in laboratory conditions may result in compromising of welfare of the NHPs. Exportation of live subjects have also become more difficult in recent years due to that fewer airlines are willing to carry them. This has opened up an increased need for high standard primate facilities in source countries. A NHP centre can be a valuable asset for the local economy, since employees with specialist competence are required and work for local sub-contract companies may also be generated.
The magnitude of research designed for publication conducted in different Asian settings will reasonably reflect availability of NHPs and funding, and to some extent the differing public opinion and ethical review process. There may be original research conducted in Asian countries that have been published in journals not covered by ICI Journal of Citation Reports. NHPs have also been used for vaccine production at governmental centres. Contract-based research is conducted for multinational or national companies in various industries or organisations. The scale of such research is difficult to assess externally, since little, if any, of this work gets published. Future surveys on the use of NHPs in research in Asia should take this into account.
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