Before firm conclusions and recommendations are drawn about preferred forms of collaborative research, this draft will be circulated to members of the Project Steering Committee. In order to provoke comments and discussion, some tentative conclusions are drawn and issues identified in the paragraphs below.

          We may start by reflecting on our findings on the points in the comparative framework we have tried to apply to each example in Section III.

1. The scope of the program along the spectrum of research needed to deal with a disease

          Only the international programs, ICDDR/B and TDR, and the schistosomiasis program of the Clark Foundation seem to accept responsibility for research across the spectrum. TDR and the Clark Foundation have mechanisms for establishing and amending strategic plans, agendas of research topics that seem most promising.

          Of the U.S. Government-supported programs, the Department of Defense laboratories operate along the widest bands of the spectrum, from seeking to understand the biological nature of the pathogen to devising methods of human protection from the disease. The military labs fall short of the international programs and the Clark approach by having a limited concern for epidemiology, the economics of protection, and the sociology and environment of the village. In devising protective strategies, the military scientists can assume standards of sanitation, disciplined conduct, and financial resource availability for the population at risk that do not prevail widely in the endemic countries.

          For the Government as a whole, there is no unit responsible for monitoring the status, defining the research frontier and devising research strategies, or formulating comprehensive policies for dealing with tropical diseases, except within the mandates of individual agencies. An explanation for the absence of coherent, targeted efforts may be that the Government does not consider tropical diseases to be of great concern to this country, except as they endanger U.S. citizens abroad or threaten to approach our shores. Another explanation may be that a comprehensive approach to one or more of these maladies would require more resources than the Government wishes to supply. Two other views encountered in preparing this paper warrant discussion by Steering Committee members.

          One opinion is that the path of scientific discovery cannot be charted; it is difficult to know what line of research will produce knowledge of value in understanding or protecting against as disease. Hence, it may be unwise to attempt to formulate strategic plans for attacking diseases.

          The second view is that scientific advances are not required in order to bring most tropical diseases under control. A hundred years ago, morbidity and mortality rates were as high or higher in Europe and the United States as they are today in developing countries. The technologies and human behavioral changes needed to reduce Third World rates to the level of the advanced countries are known: it is simply a question of investing in sanitary infrastructure, clean water, and education. From this point of view, research expenditures on trypanosomiasis are justifiable in order to advance our understanding of the immune system, without implying commitment to the pursuit of protective substances against the disease. Science should go where the best scientific investigators want it to go, not where administrators or politicians or development promoters try to push it.

2. The degree of collaboration with scientists and institutions in developing countries

          Scientifically, the most productive institutional collaboration probably occurred between the Cholera Research Laboratory in Dacca, and NIH and CDC in the United States. They were all American institutions, basically, but the relationship was productive because the quality of the work was outstanding, the substance of the work was at the advancing research frontier, and each institution brought something of value to the process. CRL gained from access to first class staff and CDC gained valuable epidemiological field experience for a generation of young workers. NIH also gained field experience for its staff, but probably valued the relationship less highly than did the other two institutions.

          Currently, the GND program of the Rockefeller Foundation and the ICIDR program of NIH include good models of collaboration on a limited scale and on an abbreviated segment of the research spectrum.

          Only three laboratories in rather advanced developing countries were selected as GND grantees. Collaborative relationships with institutions in the poorer countries are much more difficult to sustain, although the Michigan State ICIDR in the Sudan appears to be productive.

          The TDR program of WHO, although attuned to the interests of developing country scientists and intended to build Third World research capacity, falls short of the collaborative ideal because mechanisms for supporting long-term relationships between laboratories in advanced countries and those in endemic countries have not been established. However, it is worth noting that training and grant support from TDR has facilitated much collaborative work resulting in joint publications.

          The military labs abroad and Gorgas, although not completely devoid of collaborative relationships, are the poorest examples among those studied.

          As a general point, the investigator-initiated, peer-reviewed, competitive grants programs that constitute the bulk of the funding for medical research are unlikely to spawn many collaborative projects. Communications problems, language factors, and differing research traditions are likely to complicate efforts to win highly competitive awards. Programs such as ICIDR which require collaborative relationships would need to be expanded if the collaborative process were to be encouraged.

3. Results, in terms of the impact on our understanding or controlling a disease

          American medical research seems to operate on a version of the laissez-faire principles that govern our economic thinking: each investigator, in pursuing his or her individual research interests, will maximize in social terms the value of the research funds available. In the search for unique research topics, the theory might go, proposals will emerge to fill every perceivable gap in the advancing research frontier. Overly structured or narrowly targeted research designs, on the other hand, would distort the allocation of brainpower, channeling research along beaten paths into the unknown, but leaving large wilderness areas in between.

          The quality and productivity of the American medical research establishment makes it difficult to dispute this approach, if it is a fair approximation of guiding principles, but perhaps the system depends for success on a large number of active investigators. Where resources are scarce and investigators few, the targeted approach may be a more efficient strategy.

          Some types of experiment, which may be vital to linking different segments of the research spectrum, donít fit well into the existing array of programs and institutions. For example, the Rockefeller Foundation for some years carried out experiments in St. Lucia, carefully costing out various approaches to reducing infection rates from schistosomiasis on the island. Out of these experiments came valuable information that allows policy-makers to choose among alternative strategies for controlling the disease, taking into account environmental factors and resource availability.

          That type of experiment would be unlikely to be funded in military laboratories, where marginal costs of control alternatives are of minor significance, or in Gorgas, which concentrates mainly on the diseases of Panama. Nor would an ICIDR grantee be likely to undertake such an experiment, given their biomedical orientation. Possibly AID would fund such a program, although no parallel example comes to mind.

          The point is that our present federally-funded programs and institutions are not designed to track a tropical disease problem from its biomedical origins through to the point of choosing among alternative protective practices. There are gaps in the spectrum, and no agency has responsibility to identify or fill them.

4. Results, in terms of enhancing individual and institutional capacities in the U.S and abroad

          The creation of American capacity for tropical disease research warrants separate treatment from creating Third World capacity. The military medical research system seems by far the most successful U.S. program for building and retaining U.S. capacity for work on tropical diseases. The ability to offer extended field laboratory experience to career employees permits the Army and Navy to develop reservoirs of trained manpower, and to deploy the manpower wherever the needs of the service dictate.

          The Cholera Research Laboratory, before it was internationalized, deserves second ranking in terms of U.S. capacity-building, and first rank among U.S. efforts to build Third World capacity. The remarkable CRL success in offering field experience to so many people who remained in the tropical medicine field may be attributable to the organic links between CRL, NIH, and CDC, and to the fact that research at the lab was recognized at the time to be focused on an important and rapidly advancing set of issues.

          The ICMR, ICIDR and GND programs all offer or offered excellent field experience for American researchers, although in limited numbers and without strong career opportunities.

          Gorgas, situated in a tropical area, itself represents an institutional capacity for work on tropical diseases, although its value could be substantially advanced had it an assured supply of bright young researchers for residencies at the lab. This could perhaps be accomplished through links with more American universities, although Gorgas would require additional funding.

          Turning to American efforts to develop Third World capacity for research on tropical diseases, the CRL is the most notable example. CRL was built largely with foreign assistance funds, with a hefty assist from blocked local currency under the PL-480 program. For several reasons, the experience is unlikely to be repeated. Blocked currencies have for the most part been exhausted, and long-range institution-building efforts at AID have largely given way to activities with more immediate and direct pay-offs, at least in theory.

          The GND program does not attempt to build new institutional capacity as such, but in Bangkok it is benefiting a research institution built years earlier, with assistance from a previous Rockefeller Foundation program designed to strengthen medical faculties in selected Third World universities. That same program helped shape the medical faculty at Universidad del Valle in Cali, where the Tulane ICMR was initially based. Institution-building programs like the earlier Rockefeller effort are very long-range and expensive undertakings, no longer popular in foundation or government circles. Whether there are shorter, less costly, ways of building the same level of local competence remains as yet unclear.

          The ICMRs in Cali and Kuala Lumpur seem to have left lasting legacies in the institutions where they were based. The ICIDR grants may have similar results, although it is too early to tell.

          Gorgas has not seen local or regional capacity building as a major part of its mission, although that could in future be a valuable role for it to play. Again, additional funding and a new outlook would be required.

          The U.S. record in developing institutional and individual capacities for tropical disease research thus seems sporadic and not one in which the nation can take pride. No agency has a clear mandate for Third World capacity creation, and there may not even be agreement that building research capacity should have priority over other activities, such as conducting research programs or carrying out disease control projects, if additional funds were available.

          Even if a pool of funds were earmarked for building tropical disease research capacity, it is not clear that there is an agreed course of action to follow.  Unlike agriculture, the medical research community does not seem to have thought through the pattern of national and international research establishments that would be most effective in dealing with tropical disease problems. To someone coming fresh to the scene, it appears that the tropical medicine community is 20 years behind its agricultural counterpart in conception, planning, organization, and funding.

Other Issues

          Going beyond the comparative framework, some additional issues come to mind, some of which the Steering Committee may wish to address:

            Are there tasks to be done requiring collaborative efforts in developing countries for which U.S. institutions or manpower are uniquely or best able to accomplish?

            What national interests would be served by additional efforts?

            Are prospects unusually good for rapid progress in developing new technologies or applying them in the field if more funds become available?  Are some research technologies underemployed on tropical diseases because of lack of funds?

            Given present levels of funding, is there an appropriate balance among expenditures for biomedical research in the laboratory, vaccine and drug development, epidemiologic research, field-testing of products, and clinical research?  If 25% additional funds were available, where on the spectrum should they be applied?

            NIH, DoD and AID each fund tropical disease research in pursuit of its own mandate. We have found no suggestion of wasteful duplication of effort, but there is some doubt that the sum of the fragments adds up to complete coverage of the uses of tropical disease research in the national interest. Are we missing medical, humanitarian, foreign policy or other gains by not having a comprehensive policy on tropical disease research?  Do the legislative authorizations for each agency encompass the range of our national interests?

            Is an international medical research budget needed, or would it become an early target for congressional or executive budget cutting?

            Does the present distribution of American overseas laboratories and collaborative research programs offer adequate access to American scientists for field research on tropical medicine?  Is the geographic distribution of existing facilities appropriate?  Are there adequate opportunities to use existing facilities?

            If additional U.S. resources for tropical disease research become available, should they be used to bolster existing international research programs (TDR, DCC, EPI), increase research grant availability through NIH for tropical and parasitic diseases, increase contract research on specific diseases through AID or DoD, strengthen the military overseas laboratories, build Third World research capacity through AID, or mount some new programs or institutions?

            Are there ways in which international research programs and U.S. research efforts can be designed to give greater benefit to institutions in developing countries?  Are there useful models or lessons to be drawn from international research programs sponsored by other industrialized countries?

            Is the networking approach employed by WHO in TDR and CDD the best use of existing international resources, as compared with an international centers approach?  If significant new resources were to become available internationally, should they be used to expand existing programs, add new networking programs, or establish disease- or problem-focused international centers?

            Are the U.S. military labs abroad likely to remain viable in political terms over the next 10-20 years?

            Do military purposes served by the overseas labs require military control over them?  Could they serve as well if linked to NIH? If internationalized?

            While under military control, could the overseas labs serve a wider range of U.S. interests by giving greater access to American researchers?  By undertaking local capacity-building projects?  By increasing clinical research?

            Would the Gorgas Memorial Laboratory be strengthened by better linkages with one or more U.S. labs, based either within a university or a federal agency?  Could or should it be internationalized?

            On balance, has the narrowing of focus on infectious diseases strengthened the overall value of the ICMR/ICIDR programs?  In what ways?

            Should NIH set up its own overseas laboratories?  Should CDC have overseas facilities and an international mandate?

            Can the private foundations generate new large-scale national or international research efforts on tropical diseases?

            Should ICDDR/B be seen as a model for other international medical centers?  Should it be seen as more of a local or regional institution?

            Can or should the smallpox eradication campaign be used as a model for other vertical international campaigns?  For an expanded immunization program?

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