Session 7
Unresolved Issues



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International Perspectives: The Future of Nonhuman Primate Resources Session 7 Unresolved Issues

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International Perspectives: The Future of Nonhuman Primate Resources Session 7: Panel Discussion Participants: John L. VandeBerg—Session Chair, Southwest Foundation for Biomedical Research, USA Christian R. Abee, University of South Alabama, USA John Hearn, Australian National University, Australia Hilton J. Klein, Merck Research Laboratories, USA William R. Morton, University of Washington, USA John G. Vandenbergh, North Carolina State University, USA QUESTIONS AND ANSWERS DR. VANDEBERG (John L. VandeBerg, Southwest Foundation for Biomedical Research): I reflected this morning about the proceedings of the workshop, in which there has certainly been one recurring theme, which Dr. Hearn introduced and probably all of the speakers reiterated: that we do have a crisis and that actions are urgent. The most obvious component of that crisis, of course, is the shortage of nonhuman primates for biomedical research, especially rhesus monkeys, at a time when the opportunities for solving global health problems are far greater than they have ever been in the past, partly as a consequence of the revolutions in genetics, genomics, and molecular biology. This is also a time when entire societies of some developing countries are being destroyed by AIDS, superimposed on other infectious diseases that impose a huge burden of

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International Perspectives: The Future of Nonhuman Primate Resources morbidity and mortality in many of those countries. However, the basis of crisis is much more complicated than simply a shortage of monkeys. We have heard about many other aspects of this crisis at the workshop. We have heard about insufficient infrastructure for breeding monkeys, that more monkeys could be produced if infrastructure were expanded. We have heard about insufficient infrastructure for conducting experimental research, particularly as we have new needs with the emerging infectious diseases and the bioterrorism initiative. We have heard about a shortage of veterinary pathologists and laboratory animal veterinarians, trained to work particularly with nonhuman primates. We have heard that species other than rhesus are poorly characterized, including many of their basic biological characteristics and specific characteristics that are pertinent to their use and potential as alternatives to rhesus as models for some diseases. There is also a lack of reagents for many of those species. We have talked about difficulties in transportation. It is difficult not only to get monkeys transported around the world but also to have them transported on longer journeys with more stops. These journeys are certainly detrimental to the welfare of the animals. We have heard about regulatory burden: too many regulations and too little flexibility are impediments to research and to establishing breeding colonies in some other countries. We have heard about problems related to conservation of nonhuman primates and have discussed strategies for aiding the conservation efforts in tandem with increasing our biomedical research capabilities. We have also heard some encouraging news about ramping up the supply of macaques from captive bred colonies in China and Mauritius, the availability of vervets from St. Kitts, and the potential of producing rhesus in Nepal. We have heard about contributions to the conservation cycle in Mauritius and St. Kitts as a consequence of the supply of animals for biomedical research. We have heard about progress in the development of SPF colonies and the establishment of Chinese-origin rhesus as potential alternatives to Indian-origin rhesus for AIDS-related research. We have heard about progress in genetic and genomic research with nonhuman primates, which will accelerate progress toward preventing human diseases. So the questions of this session are, where do we go from here? What are the unresolved issues that have been raised at this workshop, or perhaps have not yet been raised or need to be raised in relation to the issues we have discussed? By what mechanisms can we proceed in the months ahead, perhaps over the next few years, to resolve these issues? I would like to ask Dr. Hearn, who began this meeting with the superb overview of many of these issues, if perhaps he would comment,

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International Perspectives: The Future of Nonhuman Primate Resources having listened to these last 2 days of deliberations, on what he sees as the unresolved issues. DR. HEARN (John Hearn, Australian National University): Thank you very much, Dr. VandeBerg. Ladies and gentlemen, I find a sense of excitement, having been present here in the last 3 days at the research initiatives, the infrastructure needs, the potentials for really good new science and for conservation, as well as the prospects of partnerships both within the United States as a national program and internationally. In recalling the theme of my comments to you earlier, I would simply like to highlight a couple of those issues for your consideration, again, starting with a sense of priorities and ending with a sense of partnerships. I believe that we have been privileged to see some important new data at this meeting. In a sense this meeting is unusual. It has given us a reality check on a number of areas of primatology and has given us a chance to look forward. I would like to thank ILAR, Dr. Joanne Zurlo, and Kathy Beil again because I think an important meeting like this might be restaged as a strategic reality check every 2 to 3 years, perhaps in conjunction with the Primates Society. In itemizing a few items and endorsing the ones Dr. VandeBerg mentioned, I would describe the issue of AIDS and the need for primates for AIDS as a crisis. However, I think we need to see it in context. It is also a crisis of diminishing the abilities to develop other fields. I was not entirely convinced from what we saw that there were major problems with the Chinese rhesus in terms of the study of AIDS. It is necessary to look at both the Indian and Chinese rhesus. I think we have tended in the field to become almost obsessive about the rhesus for obvious reasons. We have so many more data, fundamental data, on reagents. I endorse the issue you raised, that we really need to make an effort for the reagents in a few other species to retract the spotlight from the rhesus as a limiting factor. I will not repeat the areas that I discussed before, but I was impressed with the work now coming through in genetics with the potential for functional genomics and the ability to define the animal much more clearly. We can define required traits for experiments and reduce the number of animals, in many cases, by having more defined approaches. Likewise, from applications of colony management and studies in the field of groups of primates, endangered or others, we can get a faster assessment of their endangered status and the potential for their breeding as a result of that crisis. I believe the laboratory and field are currently overworked and overfocused in our own questions. It is necessary to survive, to publish, and to deliver the quality we have in each of our fields; however, I wonder whether we should be spending a little more time thinking about the laboratory field interface. There is a lot of human primate interface with

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International Perspectives: The Future of Nonhuman Primate Resources the issue of emerging diseases, particularly in some areas of the world such as the Amazon, Congo, or Indonesia. In those areas there are existing primate facilities nearby in Africa or South America or Asia that can partner with those centers to develop our knowledge base of potential emerging disease and the epidemiology might be required. I think with clear focus on particular questions in virology and other zoonoses, we might learn a great deal. I was also encouraged about the new initiatives to set up cell banks and develop stem cells from origins other than embryonic ones. I think we might hear about those initiatives shortly. Obviously, the alternative issue to the rhesus is very important. I suggested in my talk two or three species from each of the major continents that might provide the alternatives both in general laboratory primatology and also in niche species, such as aotus for malaria and some of the ones we heard of in the program. I was concerned and rather surprised to learn that the NIH budget has doubled in the last 5 years whereas the primate and special centers’ budgets have remained relatively flat. While I appreciate that much of that money is targeted, there is a question as to whether the primate centers are participating fully or able to deliver the best science. It seems strange to me because I know the quality and the performance of the primate centers, including the national and specialist centers. I hope that trend can be reversed, which is necessary in terms of equipment, PC, three or four facilities, and so forth. To repeat another point I made earlier, we need to put more funding into special targeted field studies in the species that are utilized principally in biomedical research in an effort to understand more of their natural biology. It is a sort of dream that if you put 2% aside from the budgets into the general fund, which would be peer reviewed and accept only top quality work, I believe we could enhance the field as a whole: 2% probably would become $4 or 5 million. If industry, as major users of primates, also were to match that amount at a level of about 2%, the total could build up to about $15 million. You could make a major impact on conservation in captivity and in the wild of primate species in that way. That approach gives us, as biomedical researchers, greater power and understanding of the primate species we study and of ourselves—for industry. Although it may not be immediately attractive to the industrial culture to do such a thing, I think it would pay off rapidly. So the state-of-the-art issues are of genetic definition, of clearer transfer of research into the human now that we have more noninvasive systems, and of international collaboration. Such partnership is critical because all of us are very pushed in our own fields, and we need a meeting such as this as well as follow-up action to form those partnerships. It all comes down to practicality and people understanding each other. If the

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International Perspectives: The Future of Nonhuman Primate Resources primate centers, and I include the special centers, each had one or two partners elsewhere in the world relevant to their specific fields, I think we could really see a “rising of the tide” for everyone in the field. DR. MORTON (William R. Morton, Washington National Primate Research Center): I would like to summarize what I think are a few of the unresolved problems that require our continued work. They are in no particular order of importance, but they all are significant. First, there are huge problems regarding transport of nonhuman primates, which have not been resolved and are getting worse. We identified a few airlines in Dr. Hsu’s presentation, and the primary carriers are all southeast Asian now. We can rely on very few domestic airlines to carry primates in the United States. I think we need to discuss this area and we need to resolve in some way whether we will have reliable, timely, quality types of transport capabilities. Second, there needs to be more investment in conservation-oriented programs within the research field. Conservation efforts Dr. Mittermeier described last night should be increased within the established research arena, such as the national primate center’s program. We have great difficulty in convincing site reviewers and grant reviewers of the need for that commitment because there is such a great focus on the end product, of specific research programs that focus on molecular biology of the AIDS virus and the molecular advances in neurosciences and imaging and all of the things we know are important. Unless we pay attention to and invest in the basics of conservation and field biology, I think we are not going to be successful in the future. Third, we all have focused on the need to look at other species. We all know there is a great shortage of the Indian-origin rhesus monkey, so we need to look at other species; but to do that, we need to educate the researchers. Everyone in this room is of like mind, for the most part. It is the research community, the people who use these animals, we need to convince that they can have alternative approaches to other species, other methods. That is the real crux of this whole argument, and we need to communicate with those people in some way. They need to be sitting here in this room and they are not. I think that is the major problem on which we need to focus. Lastly, we have heard again and again that there needs to be a larger investment in the infrastructure of facilities that maintain and handle these primates, and we should be in the forefront in thinking of the way these animals will be handled in the future. That positioning calls for a huge investment in new facilities, rethinking and retooling the way we house these animals, which can only come from a commitment from NIH and other like-funding agencies. I think we need to talk about those unresolved issues, not just here but into the future.

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International Perspectives: The Future of Nonhuman Primate Resources DR. KLEIN (Hilton J. Klein, Merck Research Laboratories): I believe this meeting was very important because it showed that there is a high level of cooperation and willingness to discuss these issues in a forum like this on an international basis. This is a very positive sign. Like Dr. Hearn, I am hopeful and excited, and I think this cooperation gives us the power to deal with some of these problems that each one of us has dealt with in our individual sessions. From the microbiology point of view, as it relates to Dr. Morton’s comment about infrastructure, there is a very important need for standardization, not only for the tests we would use to define a specific pathogen animal for biomedical research but also for the test methodology in the reagents. That step is really the next one in all of this. The other aspect that has changed from the past in our world of using monkeys is a very important need not only to integrate the microbiology to find the SPF monkey but also to learn how to maintain the microbiologic status when we now must profile them genetically. Combining this profile with the behavioral aspects in an integrated fashion to craft an SPF colony and redefine it is an important aspect of biomedical research’s future. I think it is one of the big challenges that is often overlooked. It is very obvious, but not stated. I think with the resources, conservation aspects, and the true clear-cut need, this is an exciting time for us. The monkey is really a strategic element of biomedical research, and I think we have the resources to make advances for society as long as we give it the priority that it requires. I think integration and cooperation are essential to making this work. DR. ABEE (Christian R. Abee, University of Southern Alabama): I will begin simply by reminding everyone that 1978 was the last time we created a national primate plan, when we looked at all of the primate resources and how they should be used in biomedical research and then tried to think forward. Over the years that I have been in this field, I have found that funding agencies that support the kinds of things we are talking about wait to act until there is a big problem, rather than addressing it as a prospective thing. That approach creates a serious problem when it comes to primate resources. You do not instantly breed up a national supply of macaques or of neotropical primates; it takes years to do that. If you wait until you have a serious problem, you have waited too late, and it does have a very negative impact on biomedical research. So part of what I hope we can do with this meeting and perhaps meetings in the future is to try to guide our funding agencies and make them aware of what needs to be done before it is too late in some cases. One other thing that we need to think about doing is to look at alternative species. Although there is very little or no funding to explore alternate species, it is very expensive to do primate research regardless of the

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International Perspectives: The Future of Nonhuman Primate Resources species that you are working with. Shortages of primates for research exist not only with rhesus monkeys but also with squirrel monkeys and aotus owl monkeys, for use in malaria research. I also believe that we need to work harder on partnerships with source countries in developing primate resources. Both from what I have heard at this meeting and from what I know from the field, very positive things are going on in Asia. However, much less is being done in South America, for instance, with neotropical primates, aside from the Peruvian primate project. There really is almost no development of primate resources in South America. I will close by thanking the speakers who came from six continents to talk with us about primate conservation and supply and to share their thoughts. I believe this is an excellent start for us to begin thinking about how we can strengthen partnerships with our colleagues around the world, and particularly in source countries. DR. VANDEBERG: I think I heard a potential recommendation when you talked about the national primate plan. I had forgotten how long it had been—almost a quarter of a century—since we had a national plan. It is shocking to me that we have been going from year to year, from study section to study section, with little continuity and with no real comprehensive plan to address the potential problems and potential opportunities of primate research. What do we need to do years in advance of having the resources that we need because of the long generation time and the few number of offspring produced by nonhuman primate species? Are you suggesting that we consider a national primate plan? DR. ABEE: Yes, I think a national primate plan is important because it will not only help us understand the need for primates in research globally but it will also provide guidance to funding agencies as well. DR. VANDEBERG: It seems that many of the issues we have discussed at this workshop are very complex, and clearly we are not going to solve the problems in a couple of days here. We are going to uncover many of the problems, but it seems that many although not all could be handled well in a plan that is carefully developed over some period of time by a diverse group of experts. DR. KLEIN: As Dr. Abee and I discussed some time ago, and based on what we heard yesterday about conservation and what is going on in threatened parts of the world, I would suggest calling it an international primate plan. I think it is more appropriate in this community and in this era than a national plan. DR. VANDEBERG: I think you are absolutely correct. It has been very clear from the discussions at this meeting that the world is very integrated in its use and supply of nonhuman primates, and an international primate plan makes much more sense than a national primate plan.

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International Perspectives: The Future of Nonhuman Primate Resources DR. HEARN: I agree that a plan of this sort is vital because it opens opportunity. I suggest providing broad guidelines for 5-year and 10-year objectives and then proposing activities for the next year or 2 years to work toward achieving those goals. Then you revisit it after 2 years and update it. DR. VANDEBERG: The audience should feel free to comment on desired aspects. DR. RAO (A. Jagannadha Rao, India Institute of Science): This meeting is a very useful for my understanding of the problems. I really appreciate the idea of an international primate plan. As all of you know, primates are time consuming to breed in sufficient numbers for our use. One way I have been working to impress my country is to attempt to combine programs, as in Indonesia’s and Washington University’s collaborative programs, so that the infrastructure in source countries can be combined. The standards can be acceptable internationally. Collaborative programs can be carried with the conservation biologists so that certain things are immediately evident. To allay any suspicions or fears, the best thing is to have immediately visible results as far as certain endangered species are concerned. Perhaps programs that are relevant between particular countries, such as between the United States and India, can be developed under improved conditions as a first step so that the animals can be used as they are needed. Transportation problems would be solved because the plan would be economically viable, and maintenance could be improved through initial goals to soften the rigid conditions so that eventually, perhaps 5 or 10 years from now, conditions are improved and export is possible. I believe the shortage of rhesus monkeys, macaques, and vervets, can be solved. DR. BECK (Jeanne C. Beck, Coriell Institute for Medical Research): I want to thank the organizers for an extremely interesting several days. There is a lot of information that we can take home from what has been presented. I want to tell you that under contracts from the National Institutes of Health and the National Science Foundation, Coriell establishes and distributes cell cultures for use in research. From the discussion of the last few days, it would seem that as nonhuman primate resources become scarce, a more vigorous effort to bank its cells and tissues from these animals is essential. Although cell cultures could not be used for all of the studies suggested, they would be useful for genetic studies, comparative and functional genomics, and aging and normal biology. From the tissues we have obtained from the Washington National Primate Research Center, we have been able to establish differentiated cell lines and to isolate what I consider something very exciting—multipotent adult stem cells from both

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International Perspectives: The Future of Nonhuman Primate Resources fat and brain. Dr. Hearn mentioned primate partnerships, which I think we should consider banking tissues and establishing cell lines. Furthermore, in countries where export is precluded with the appropriate permits, it would be possible to collect samples and establish cell lines from these animals. Although this method will not solve the shortage, it may alleviate some of the shortfall. I would like to mention that we recently obtained funding from the National Science Foundation to set up a bank of cell lines from primates. We hope to have a male and female from each species and then also to include some species in depth. One of the very important things I think this grant permits us to do is to work with range countries and to do capacity building. I would urge you to consider banking these incredibly valuable animals for the future. DR. VANDEBERG: Thank you for informing us about those activities. Certainly at our primate center we have discussed in the past the idea of establishing and maintaining cultures from some of these pedigree baboons, especially some of the original founders. Some of them are dead now. Although 15 or 20 years ago we thought we had collected enough blood samples from them to have enough DNA to last as long as we wanted, we now find ourselves short of DNA, with a loss of that opportunity for future genetic research. If we had immortalized cultures or even had established cultures from those animals, it would have been very valuable to the future of nonhuman primate research. Our center would be delighted to work with you on that initiative, and I expect the other centers would also be so inclined. DR. ERVIN (Frank Ervin, McGill University): I think that is a wonderful idea. We do have cultures on all of our animals that have been in our hands. However, I want to mention something quite different. I am slightly puzzled by something Dr. Morton said. I suspect that the investigators should not necessarily be at this meeting but instead should be subject to you telling them something about what they should do. I have a proposition. I will donate up to 20 animals, if you will pay the transportation, to any approved project that will substitute a species different from a rhesus, which in your scientific judgment does not require a specific species. I happen to know that in Washington there are a number of such projects in which very competent scientists are using whatever monkey they learned about during graduate school. DR. MORTON: I think that is a great comment. I agree with what you said, that these researchers need to hear more of this. Although they hear it from us and from people who are not here (e.g., veterinarians) they tend to take it less seriously than if they were hearing it from a national or international gathering like this, which is focusing on these problems. They need to understand these problems. I think that the point you made

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International Perspectives: The Future of Nonhuman Primate Resources about trying other species in what might be very acceptable ways for specific experimental projects is something we would very much like to do. However, as I think someone has pointed out, these programs are expensive to operate, and there is often a lack of funding for infrastructure to support them. Money is necessary to support these exploratory investigations to compare and contrast different species as to when and how they can be used. We saw a great example of it yesterday. Dr. Marthas compared and contrasted Indian-origin Chinese rhesus and made her conclusions from that. We need to expand that approach and look at the African green, the fascicularis, and other primate species that might have greater availability not be as threatened as the rhesus monkey. I am in total agreement with you and would very much like to work together. DR. VANDEBERG: That offer is extraordinarily generous. To follow up on what Dr. Morton said, I believe that funds should be dedicated to that purpose if alternatives are to be seriously tried. We are never going to get funding from a study section to try out a new species. Unless there is an administrative commitment to support the development of new species as models, it will not happen. The investigators do not have the money to do it and they cannot get the money to do it. Your offer is certainly generous. Perhaps we will stimulate some further thought on how we can obtain the other resources needed to explore the vervets as well as some other species as potential models. DR. ROBERTS (Jeffrey A. Roberts, University of California—Davis): Relevant to the Chinese-Indian project that was done at Davis, I want to mention that it was subsidized in part by a specific primate center base grant to look at the comparative biology of these two species. That subsidy is a critical element of the base grant function. Additionally, in terms of educating the investigator or getting the message out there and also in the context of developing an international primate plan, I believe it is important to obtain some consensus or body of information from the different NIH institutes about primate demands and model leads. I know there have been some efforts along these lines, but different meetings seem to focus on different demands (e.g., NIAID on AIDS and NIA on aged primate models). I think that if we had greater consensus or coordination from NIH regarding the expected future primate demands, we would benefit in terms of planning and the opportunity to educate program people at the different categorical institutes about the availability of different species. I think NIA has been successful with studies that have looked at biomarkers of aging and the aged rhesus macaque. It has alerted them to the resources available in the aged baboon, the aged squirrel monkey, and many other species available for aging research. Those resources also offer the opportunity for comparative studies that are sometimes the most infor

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International Perspectives: The Future of Nonhuman Primate Resources mative. I think as we look at this, we will definitely get more of a sense of a demand from the community. I also think that educating the program officials about the availability of African greens, cynos, and New World primates will be beneficial in interactions with investigators. DR. VANDEBERG: It seems to me that Dr. Roberts’ suggestion is an excellent idea for one of the potential charges to a committee developing an international primate plan. Someone must assemble that information. It takes some effort, and it seems to me that a committee could ferret out that information from the many institutions of NIH. Certainly that could be one of the components with which to charge such a committee. DR. ROBINSON (Jerry Robinson, National Center for Research Resources): Along those lines, I would like to bring to your attention that we have received a request from the Secretary of the Department of Health and Human Services to form an interagency committee to review the total needs for nonhuman primate research. That committee had its initial meeting 1 or 2 weeks ago, with representatives from CDC, Department of Defense, and FDA as part of the committee. DR. VANDEBERG: Is that group going to do what Dr. Roberts was suggesting and learn from all the NIH institutes as well as other government branches what the proceed needs are for nonhuman primates? DR. ROBINSON: Exactly. Melding into that information is the NCRR’s recently completed survey on which I reported, indicating that approximately 13,000 nonhuman primates were used by NIH grantees in 1999, and we know that need is increasing. In addition, I would like to mention that even though we have not publicized this information, we at NCRR and the Office of AIDS Research have formed a small working group, which is convening today to look at this very issue. We want to look at the use of Chinese versus Indian species in AIDS research. We are also trying to look at alternative species to alleviate the pressures on rhesus macaque. We are bringing in some experts, many of them are here at this meeting to help us look at the possibility of using the baboon, the pigtail, the vervet, the cynomolgus, the squirrel monkey, tamarins, and the marmoset as alternatives species in other research. This meeting is open and will be in Room 150 beginning at 1:00 pm. DR. BAUDOIN (Mario Baudoin, Ministry of Sustainable Development and Planning): I would like to endorse what Dr. Rao said regarding the need to work on partnerships to be able to build permanent institutions within source countries. The result will be continuity and programs that will shift perceptions. In addition, for instance, we want to give permission for squirrel monkeys to be exported from Bolivia. We have a request for 1500, and if we want to do things well, we should have an idea from where in Bolivia they will be coming and what the impact of the extraction will be in Bolivia. We do not have the basic data about popula

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International Perspectives: The Future of Nonhuman Primate Resources tion densities within Bolivia to make that recommendation. It would be helpful to have even a very small investment and some basic field research about population densities in the source countries. In the case of the squirrel monkey, even a minimal amount of genetics will be informative because we do not know from precisely where the original squirrel monkeys came that were exported in the 1980s and have been good models. Making a small investment in those things would be a great contribution to having programs work well. PARTICIPANT: First, I would like to congratulate everyone on this eye-opening meeting. I agree with the people who are from the less developed regions of the world. I think there is a difference between saving and investing. I know that the stock markets are not doing very well these days. Essentially, if we look at the future, and the less developed regions of the world, we see that those of us in countries that have the monkeys also have a very large gap in technology. We cannot contribute to vaccine development or science unless we choose to be partners. We have to start addressing those questions if we want to invest in the future and be partners in research as well as in supplies of material. The Caribbean region is particularly important. Not only in South America (and I am in full agreement with what my Bolivian colleague said) but also in the Caribbean, the second highest incidence of AIDS exists. Obviously some vaccines are going to be tried there in monkey experiments. However, those countries should not be used only as human resources for testing vaccines but also maybe as intellectual partners in the science development. I am sure there are many Latinos who are quite capable of elaborating on that subject. We have learned from yesterday’s lecture and from comments here that we are in a global world and are all partners in science. I believe we need more integration, dialogue, and inclusion. I think the time is right for forming international committees for transportation issues and for future events. We have an AIDS epidemic now and we will have other epidemics in the future. No one expected bioterrorism, and it is with us now for years to come. We need to look at the future and at investing in particular areas not only to consolidate resources but also to develop infrastructures to protect our target locations against bioterrorism. DR. SEIER (Jürgen Seier, Medical Research Council): I would also like to congratulate ILAR on a very excellent workshop. I would like to reiterate the call for forging partnerships with facilities in source countries. From the point of view of my own facility, I certainly cannot supply anyone with primates because it is not the mission of my facility. Nevertheless, it is the only facility of its kind in South Africa. We have several hundred pedigreed vervet monkeys whose importance we have heard

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International Perspectives: The Future of Nonhuman Primate Resources throughout this workshop. They are tested for a variety of micro-organisms and are pathogen free. They are looked after by staff who is qualified as in the United States and Europe. We have scientists in the facility whose postgraduate research has been entirely on vervet physiology. We have consultant veterinarians and pediatricians. The animals are in excellent quarters according to international expectations. We have an environmental enrichment program. The benefit of these important partnerships is that we have a track record of research. The profits of contract and corporate research are not put into some corporate structure or bureaucracy, but are reinvested in the animal facilities. For example, I am employing a full-time zoologist to provide environment enrichment and research and to develop vervet-specific enrichment. We are looking at stress levels in different housing conditions, for example, and the studies are entirely funded by contract research. Unlike people wondering whether or not we can use other species, we have been using the vervet monkeys for 25 years in nutrition, reproduction, and diabetes; and our results are similar to those of other people with other species. Through partnerships, although we cannot supply you with primates, we can certainly do some of your research, which will also indirectly alleviate the pressure on primate populations in user countries. DR. TARDIF (Suzette Tardif, Southwest National Primate Research Center): I would like to reiterate a point Dr. Morton made about taking this message to the investigators and educating the investigators. I would like to put forward the efforts of the primate centers regarding marmosets as an example of a way to do this. Colleagues from New England and Wisconsin and I have started to put together some educational efforts. We are going to present a symposium at the AALAS meeting, for example, on marmoset husbandry and management. We are planning a national meeting organized around the use of the European marmoset research group as a model to try to pull together investigators from NIH-supported projects and from pharmaceutical firms, along with people who can supply both marmosets and information about marmosets, to get the word out and to educate people. We will let you know how it progresses. I think a great deal of effort for individual species must originate from groups like this, composed of investigators who can put together such efforts. DR. MCGREAL (Shirley McGreal, International Primate Protection League): There is no exact definition of bioterrorism research. Because I think many people might take a favorable position on medical use, I think they also may be very concerned with the ethical implications of holding monkeys as players in the human dramas we create through our human

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International Perspectives: The Future of Nonhuman Primate Resources misconduct. I notice the increase in demand. What percentage of the demand increases is attributable to AIDS, and what percentage or how many monkeys are going to be involved in bioterrorism research? DR. MORTON: I am not certain that I understood your question, but I think you are basically asking whether we should use monkeys for the human problem we created and how they will be involved? Fortunately for us and perhaps unfortunately for the monkeys, they are the exact model that will be needed to evaluate the kinds of infectious disease that will be used as potential bioterroristic approaches. Some of these agents are already in use, and some are well known. I think smallpox is one such agent. Much of the existing AIDS vaccine work follows along those lines because of the approach. Some of the theoretical vaccines being tested are based on a type of smallpox approach. Much of that work has already been done. Anthrax obviously is one well-publicized agent, and work on the anthrax vaccine has been going on for some time. I believe that situation will just accelerate. I do not know to what degree and I do not think any of these programs have a significant number of primate uses, but I think we all expect to see other kinds of programs that deal with the “Big 5” potential bioterror pathogenic organisms. Obviously, NIAID has huge funding that has been or is being projected to prepare the nation for bioterror threats, and some of that funding will be applied to primate use. DR. KLEIN: Nonhuman primates are required as part of the proposals for at least two of the bioterrorism agents, anthrax and smallpox, to prove efficacy of antibody development and safety. It appears that industry might be considering non-nonhuman primate species to get preliminary answers to the antibody generation question and parts of the answer to the safety question. Answering some of these questions is more of a national defense priority than other things at this point in time. DR. MWENDA (Jason Mwenda, Institute of Primate Research, Kenya): I certainly support the idea of the international primate plan as a way of enhancing international collaboration. In Kenya, we have facilities that fulfill the international standards, and we have developed private models for looking at different aspects of infectious diseases, reproductive health, virology, and primate conservation. I believe there is an opportunity to make scientists aware that some of these models are available. Perhaps we could develop a list that highlights some of these models that have been developed over the years and look at their advantages or the advantages and disadvantages of some of these models to actually make people aware that these models are available. I think that would be a good way to start and would basically enhance the collaboration. My other point is about the cost of private research. We are saying that primates are very expensive; however, with the models that are currently well established, I think we could also reduce the cost of private

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International Perspectives: The Future of Nonhuman Primate Resources research by conducting the research in those resource countries where some of these models are well characterized. That approach could reduce the cost. DR. ERVIN: I want to expand on Dr. Morton’s response to Dr. McGreal’s question and simply point out that one of the silver linings of the bioterrorism research demand is that, fundamentally, we are turning attention to the development of vaccines that were formerly relevant only to the third world, or people who could not pay enough to enter as corporations. Now suddenly the first world is threatened, and we are paying attention. The vaccines are not just for evil plots against each other, but they in fact spill over into providing research and protection, we hope, for things like ebola and plague, which are not first world problems. I think there is probably a true benefit there. DR. GALLAND (Gale Galland, CDC): I look around the room and am awed to see people for whom I have much respect and from whom I have learned so much from over the years. I have only one comment because I know that many people here have the same kind of problem I have: how to convince people in management that they must plan for the future. Everyone in this room agrees with everything that has been said about conservation and setting up breeding colonies and things like that. I am talking about convincing people—the users, the end-users, and the researchers—but mostly the management people who live from year to year without knowing how much money they will have to spend or what the disease will be next year. It can be a very difficult thing to persuade them to think outside the box and to put money into breeding situations because their first question is, “How many animals can I get out of it this year?” or “How many can I get next year?” It can be very difficult. I am very interested in any suggestions that might come out of a national primate plan. They look at what they are doing now, what diseases are killing people now, what outbreaks they have now, what they need now to run this study, and so forth. That part of my job is very difficult. DR. VANDEBERG: I agree that it is a difficult part of the jobs of many of us. I think that an international primate plan should include convincing arguments to support the need to look to the longer term future rather than simply to the immediate needs of this year or maybe next year—not only to project the needs, but also to make the case very clearly that those needs must be thought of many years in advance, rather than when they actually arise. We have talked about an international primate plan. I want to suggest three other areas that I think are unresolved and perhaps do not fit into the concept of an international primate plan but that might merit a very

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International Perspectives: The Future of Nonhuman Primate Resources detailed study by panels of experts. The first area is the transportation issue, which has been discussed repeatedly. It is very complex and is a moving target, shifting all the time. Might it not be worthwhile to put some real time and effort into defining precisely what the problems are and how they have arisen and into making recommendations in relation to how they might be solved? Second, we have heard about the need for microbiological standardization and characterization. We all agree it is important, but do we all know what it means? I certainly do not. It is not my field. But do all of the people in that field even agree on the appropriate level of microbiological characterization of our nonhuman primate resources and how we could achieve standardization? Perhaps we need a group of people to invest time and effort into thinking those problems through and making some international recommendations. The third area that surfaced only briefly (perhaps in a question Dr. Hearn asked yesterday) is the question of genetic standardization. Twenty years ago, there was very little genetic research being done with nonhuman primates—very little genetic monitoring and very little genetic management. We hear increasingly about both the research and management aspects, and Dr. Hearn asked if there are any minimal standards for genetic management of nonhuman primate resources. I recall answering that “it depends on what kind of resource and what the purpose was.” Clearly if the answer is not clear in my mind, as one who has worked in genetics all of these years, it is perhaps an issue that needs to be discussed thoughtfully by a more diverse group of geneticists as well as users of animals who might be able to reach a consensus on minimal standards for different types of research and resource colonies. I mention those ideas to the group as possible future initiatives that could arise from this workshop. DR. ZURLO (Joanne Zurlo, Director of ILAR): At the risk of sounding self-serving on the part of ILAR, I do think we can offer the forum for accomplishing many of the goals that might be set as a result of this meeting. As a first example, Nelson Garnett mentioned yesterday that OLAW is definitely interested in funding a study on transportation. At ILAR Council, the International Committee has discussed the necessity of doing such a study, and so I know that OLAW will contribute some of the money. I think we can probably find resources to fund the remainder of the study, but that matter is still ongoing. Second, the issue of microbiology and genetics, and even the issue of an international nonhuman primate plan, might be topics for projects that ILAR can orchestrate probably better than many other institutions in the country in the sense that we do have contacts and working relationships with the Federation of European Laboratory Animal Science Associations

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International Perspectives: The Future of Nonhuman Primate Resources (FELASA), with the European Union, with the Pan American Health Organization (PAHO), and through the primate research centers to some of the Asian and African countries. The resources that allowed us to arrange this meeting could also allow us to serve as the foundation for working on an international plan. So, I offer that possibility, and I offer our services. I am sure that the representatives from ILAR Council who are here will underscore that offer and echo that sentiment. DR. VANDEBERG: Thank you for offering that opportunity to all of us. DR. SEIER: Maybe a small solution or part of the solution to the problem is not to transport the primates but to transport the users, unless airlines will also refuse to transport them in the near future. I think you will find that in facilities that meet your requirements for a good standard, the work will be much cheaper than in many user countries, and there will be plenty of margin/surplus for transporting the user. DR. HEARN: It occurred to me after hearing the comment from Dr. Galland that a number of these issues are articulated clearly in the 1978 plan. I think we could review the plan to see that it has some very clear and powerful language. To return to Dr. Robinson’s point, it seemed to be a surprise to some that suddenly there is a high-level committee looking at the future needs of primates in a multiagency context. Unfortunately, many of the people (and I am a cynic) who sit on these national and international level committees probably could not tell a monkey from a mall rat, but it is an opportunity for leadership. The important point is that the leadership should come from the community that has clear information. I suggest that information should be provided on primate needs in terms of numbers and endpoints of that, on the needs for primate research that furthers our knowledge, and on slightly different, more currently urgent needs on bioterror. These needs are not the same. We need clarity and we need to address all of them. I think we need clarity also in this interaction among ourselves, as scientists, biologists, biomedical researchers, and conservationists. I am always impressed with Dr. Mittermeier’s wonderful vision and the things he is doing; I am also very impressed in a meeting like this to learn that so many things are being done in biomedicine. But let us not kid ourselves that we are all “fuzzy conservationists.” We all need to take note of conservation and be conservationists in the broader sense, but let us have clarity in that the endpoints and the objectives in biomedical research and in conservation biology need to be kept fairly straightforward and simple because the communities are not all the same. Mixing them up may not always be to the advantage of either; however, I suggest that we do need to give intellectual and practical application to the overlap of those two

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International Perspectives: The Future of Nonhuman Primate Resources objectives where we can definitely synergize. The new resources in genetics can be applied in the field, as can most of the upcoming technologies for noninvasives and the possibilities of preventing disease in primates in the field with new delivery systems. These applications are all very valid, so I think we can view them as part of an international collaborative program. Finally, I believe that the process the ILAR Council has developed over the years in delivering best practice across animal sciences is a system that works extremely well for consultation and delivery of a report. To follow that process may be the best way forward here in a relatively independent way to acknowledge and integrate the different bodies from NIH, from industry, and from the international community in delivering quickly a clear and fairly simple international primate plan. DR. ROBERTS: I would like to make one comment on your references to the microbiological and genetic characterization and as one of the members of the SPF group that was supported by NCRR through OAR. Some of these issues might be a framework for an initial consideration. Dr. Mansfield may want to add in a comment, or not, as he is a leader of that group. That group will be larger with the new RFA soliciting applications that deal not only with rhesus but also with other species of macaques. Certainly we have a long way to go before we come close to the standards established in rodent biology with respect to nomenclature, disease characterization, and genetic management. However, those are goals for which we have those examples. As Dr. Tardif mentioned about thinking in terms of the long term, a rodent may require 20 generations to achieve an inbred strain. With primates, we should think 10 and 20 years into the future about what we are going to need and will hopefully have for our populations then. Certainly things will change in the meantime, but I believe the old saying is appropriate: “It’s not the plan that’s important, it’s the planning process that’s important.” DR. VANDEBERG: To conclude, I would like to offer our appreciation to several parties. First, to ILAR for having perceived the need for this meeting, having organized the conference, and having done all of the hard work to make it possible. Second, to NCRR, as the principal sponsor of this workshop, without which we could not have had it. And finally, to all of the speakers who did a superb job and pitched their talks exactly where we hoped they would. They, together with the audience, are really responsible for this stimulating meeting. I thank all of you and our panel for their comments this morning.