COLLABORATIVE RESEARCH ON TROPICAL DISEASES (1985)  p. 5  of 12

D. INTERNATIONAL CENTERS FOR MEDICAL RESEARCH AND TRAINING (ICMRT), INTERNATIONAL CENTERS FOR MEDICAL RESEARCH (ICMR), AND INTERNATIONAL COLLABORATION IN INFECTIOUS DISEASES RESEARCH (ICIDR)

          In the late 1950’s, NIH health strategists were aware that the capacity of the American medical establishment to deal with tropical diseases, greatly expanded during the war, was atrophying. Deeming it important to maintain at least a modest level of interest and competence in tropical medicine among American biomedical scientists, they made plans to establish several training centers in port cities in the United States.

          The passage of the International Health Research Act in 1960, PL 86-610, allowed NIH to expand its concept and include overseas activities. The authorization provided for international cooperation in health research, research training, and research planning, in order to advance the status of the health of the American people. Authority to engage in international cooperation to advance the international status of the health sciences was also included in the Act, but reserved to the President. As we noted in the cholera story, the delegation of that authority is enjoyed at the moment only by the US/Japan Cooperative Medical Research program, which probably doesn’t need it.

          The intent of Congress to preclude NIH from participating in overseas programs for the benefit of non-Americans was reaffirmed in congressional hearings in 1962. Congress did not want confusion and duplication to arise from the fragmentation of the foreign assistance program.

          Consequently, the ICMRT program was shaped with benefits to United States citizens exclusively in mind. The principal purposes of the program were to provide stable, long-term overseas sites for research and research training on environmental, ethnic and biomedical conditions of scientific interest unavailable in the United States. The program would increase the number of US scientists competent in biomedical research and knowledgeable on health problems in other countries.

          Four grants were made to universities in 1960 and one the following year for the establishment of overseas centers at cooperating universities abroad:

·            University of California in San Francisco, with its overseas Center at the Institute for Medical Research in Kuala Lumpur. Units were also located in the Faculty of Medicine, University of Singapore in the l960s, and in the faculty of Medicine, University of Malaya from the mid-1960s on;

·            Tulane University School of Medicine, with its overseas Center at the Universidad del Valle in Cali, Colombia;

·            Johns Hopkins University School of Medicine and School of Public Health and Hygiene, with its Center at the Calcutta School of Tropical Medicine and the All-India Institute of Hygiene in Calcutta, India;

·            University of Maryland School of Medicine, with its Center at the Institute of Hygiene and the Medical Institute College at Lahore, Pakistan; and

·            Louisiana State University School of Medicine, with its Center at the University of Costa Rica School of Medicine in San Jose, Costa Rica.

          The grants were for five years, averaging approximately $500,000 per year, a figure which continued fairly constant over the years as its value declined through inflation. One of the express purposes of the program was to provide stable bases for work in tropical medicine on which people could plan their careers, confident of continued employment opportunities. The program was never re-advertised, but the grants to participating institutions were renewed after periodic reviews. The original four universities each remained active for the full 20-year span of the program. LSU was dropped from the program in 1970 when a reduction in funding made it necessary to reduce the number of Centers. The total cost of the program was about $45 million. Successful institutions used their grants as core funding and were able to attract personnel paid from other sources. Thus the total expenditure was always much greater than the total of the NIH grant.

          The grants permitted the universities broad latitude in designing their programs, depending upon the interests of faculty members and the medical priorities in the area in which their centers were located. Although most of the work would deal with infectious diseases, other conditions such as malnutrition, genetic diseases, and population dynamics were eligible for inclusion. Interdisciplinary approaches were to be employed, including the social sciences. The program and activities of each ICMRT may be summarized as follows.

- UCSF/Malaysia (UC-ICMR). The Center conducted research on arboviruses, especially dengue because of its prevalence in Malaysia. Although usually an urban disease, scientists at the Center demonstrated that dengue infection occurs in monkeys in the forest canopy and that a previously unknown mosquito was the probable vector.

          Another important segment of the UC program was in parasitology, especially host-parasite interaction, with special attention to natural or acquired resistance of vector snails to the larval stage of human parasites. The long-range objective was to develop biological methods to control snails, the vector for schistosomiasis and other parasitic diseases.

          UC-ICMR social scientists and epidemiologists collaborated with IMR scientists in studies of Malaysian community health, ethnomedicine, socio-medical determinants of disease, demography, and traditional Malaysian medical care. The variety of peoples in the country provided opportunities for the study of abnormal hemoglobin occurrence and other genetic conditions, such as thalassemia. This work was closely coordinated with similar studies at UC San Francisco.

          Some UC-ICMR offices and labs were located in the same building as USAMRU/Malaysia, both associated with the DIR. The pattern of association was quite different, however. USAMRU research was generally quite self-contained, its own personnel working in its own labs, while UC-ICMR people were dispersed throughout the Institute working as staff members of DIR research divisions. Extensive UC-ICMR and IMR collaboration in many fields resulted over the years from this arrangement. Only a few UC-ICMR researchers collaborated with USAMRU scientists, possibly because having come half way round the world they were eager to work with Malaysians rather than Americans.

- Tulane/California. The Tulane group conducted a vigorous program on malnutrition, including clinical research on hospitalized adults and children, experimental animal studies, and field surveys. This was possible because of an unusually fine group of Colombian investigators interested in a range of nutrition issues.

          The second largest effort by Tulane was on infectious parasitic diseases, including American trypanosomiasis (Chagas disease), intestinal parasites in school-age children, and the ecology of insect vectors of parasites of man and animals. Epidemiological investigations of diarrheal disease and fungal infections were also conducted.

          A third dimension was added later to the Tulane ICMRT program, with the encouragement of the ICMRT Advisory Committee. It dealt with behavioral sciences and social epidemiology, including social psychiatry, psychiatric origins of criminal behavior, health systems, anthropology, and health service utilization.

          In 1975, Tulane changed its institutional affiliation from Universidad del Valle to COLCIENCIAS, the national research council.

- Johns Hopkins/Calcutta. We are already familiar with the work of the Johns Hopkins team on diarrheal diseases, although that was not their only, or even their primary, effort in Calcutta. Other projects concerned hepatitis, malnutrition and anemia, schistosomiasis, and the ecology of certain insects and mammals in India.

          After the move in 1972 to Dacca, their work was focused primarily on diarrheal diseases, nutrition and population dynamics. The last two years of the project found the ICMRT in collaborative research on diarrheal diseases with the Gorgas Memorial Laboratory in Panama.

- Maryland/Lahore. The most active studies by the Maryland team were on genetic variations of mosquitoes, for the purpose of devising methods for biological control of vectors of malaria and arbovirus infections. Another project dealt with the treatment of drug-resistant malaria found in Pakistan, and additional work was done on scrub typhus.

- LSU/Costa Rica. The LSU group focused on the study of parasitic infections most actively. Some work was also done on viral infections including hepatitis.

          In 1973, the training element of the ICMRT program was dropped, and the Centers became known as ICMRs. This change was precipitated by strong pressures from OMB and the Congress to reduce training at NIH.The word training in the title of any program could jeopardize its existence, so it was dropped. The training intended in the program was only meant to benefit American scholars in any case, so the change in titles may have been expected to produce little change in practice. Not so, in the opinion of Frederick Dunn, who spent seven years in Malaysia under the ICMR(T) program. The consequences of the change were enormous, in his view, the strength of the program lying in the training and developing-country experience it provided for hundreds of American health science professionals. Dropping the training was one step on the road that led to the demise of the program.

          An earlier step on the same path was transfer of ICMR funding to the budget of NIAID in 1968. Previously, ICMRT had been insulated from the research focus of any single NIH institute by being administered by the Office of International Research. Transferring the program to NIAID led to increasing pressures for emphasis on infectious diseases research, and on research as such, rather than research training. Thus, according to Dunn, work by hematologists, geneticists, social scientists, cancer epidemiologists, psychiatrists, heart-disease epidemiologists, etc. was increasingly viewed as inappropriate. The program gradually became a tropical disease research program, instead of a medical research and research training program in the tropics, as it had begun.

          Despite the size and significance of this program, it received no terminal evaluation when it ended in 1980. An evaluation plan was drawn up and discussed with the Institute of Medicine, but in the end NIAID decided not to follow through with it. As a result, we have no balanced, or even biased, document on which to rely for judgments of the outcome of this relatively large investment of research funds.

          A rather formal mid-course study of the Tulane program was conducted by Shirley B. Laska of Tulane in 1974.

          Each of the grantee institutions negotiated its own arrangements with its hosts. All found it necessary to make some accommodation to the professional needs and interests of the host institution, but there was a good deal of variety in the result. Some ICMRs were in effect American laboratories housed for convenience abroad. This was consistent with the terms of the award, but sometimes made it difficult to demonstrate program benefits to host country institutions. In other cases, such as UC-Malaysia, the ICMR was a highly collaborative association of American and Malaysian scientists working in labs and in the field.

          Tulane was on the collaborative end of the spectrum. A project advisory committee governed field activities. Colombians were represented on it beginning in 1965, and for a time were a majority of the committee’s members. In 1969, the committee was reorganized, with three members appointed from Tulane and three from Valle. All members had equal voting power. In addition, the committee had an unusual procedure whereby Valle members could veto any research proposal made by someone from Valle, Tulane, or some other institution. The Tulane members in turn could veto any proposal approved by Valle members. This arrangement assured that all proposals were deemed appropriate and important by the host institution, and that Tulane could remain responsible to NIH for the pertinence and quality of the proposals accepted.

          Tulane recognized that facilitating Colombian research and training Colombians was of major importance, not only to ensure their own welcome, but because of the dearth of other research opportunities for their colleagues. This goal was not formally acknowledged, however, because of the terms of the grant. It would not do to be perceived as offering foreign assistance.

          Even while enjoying a share in the governance of the project, and access to research funds, some of the Colombians complained that they did not have equal access to facilities and funds. Some of the Americans, on the other hand, complained about the selection process being subject to personal biases and about being somewhat isolated professionally while in Colombia.

          In general, however, the project appears to have been successful, popular and productive. Twenty-five theses and dissertations were produced in its first 13 years, and 244 publications, 22% of which first appeared in Spanish.

          Laska makes the comment that the Valle scientists considered that one of the principal values of the project was the opportunity to gain a better understanding of the medical problems of their country -- but that this “is not of special concern to the US participants, who as researchers have a greater concern for the advancement of scientific knowledge.”  This may simply represent the author’s personal judgment, but one suspects that it reveals an attitude not uncommon in the medical research community. It could account for the fact that nowhere in the rather tortuous examination of participants’ feelings about personal advantages gained from the program is there mention of the possible impact of the research on the disease burden of Colombians. That was not the purpose of the program, nor apparently was it the result.

          In addition to the Laska study, evaluative comments on the ICMR program are found in John Seal’s letter of support for the military overseas laboratories. This letter was written in 1980, when the ICMR program was already at an end, and the military laboratories were endangered, so Seal’s remarks may tilt somewhat in favor of the military model in the interests of maintaining national capacity for field research abroad. Also, Seal had had a naval career. Nonetheless, his points are instructive.

          Seal’s main point is that there is no career available in U.S. academic institutions for those with primary interests in international medical research, and that lasting competence cannot be established through grant and contract programs which do not produce tenured positions.

          As evidence he cites the fact that 20 years of stable support for four of our better medical schools through the ICMR program failed to build a continuing capacity for international work on infectious diseases. Capacity seemed instead to have declined, as indicated by the failure of three of the four schools to compete successfully for the ICIDR grant program that succeeded the ICMR program.

          This point is a bit unfair because many in the universities saw the ICMR program primarily as a training vehicle to prepare people for careers in other institutions, not their own. As for the ICIDR competition, it was a different ball game. Many of the ICMR participants were interested in medical issues in tropical countries, but not in infectious disease problems.

          Seal also pointed out that limited opportunities exist in schools of medicine for entomologists, veterinarians, sanitary engineers, or other disciplines often needed in overseas research or operations. Nor do physicians with valuable international research experience tend to stay in the field. NIH had another program from 1963 to 1969 aimed at giving overseas research experience to young physicians. By 1979, of the 23 physicians assigned through the program to military overseas laboratories, ICMRs, or the Cholera Research Laboratory in Dacca, only one remained in government and only eight in academic medicine. Of the eight, only three had a current relationship to overseas research. These figures are challenged by one participant in the program who personally knows of eight still very active in tropical medicine. This may reflect the fact that although many seem to go out of the field immediately after their initial experience, they later find opportunities for returning to it.

          In 1974, in anticipation of a full-scale review of ICMR program accomplishments before the fourth round of funding, Howard Minners, a PHS officer charged with administering the program at NIAID, wrote an article in which he broached a number of issues concerning operations of the program. Among them were the following:

·            How can the achievements of the ICMRs be evaluated quantitatively for their contributions to scientific programs and to individual careers;

·            Are participating universities able to maintain a sustained level of high quality research in the field;

·            How sharp a focus is appropriate; should each ICMR select a single theme;

·            How relevant are ICMR research programs to NIAID objectives;

·            What is the size of the critical mass needed for centers abroad; and

·            Should the ICMRs be located geographically to cover a broad range of geographic medicine environments?

          The anticipated review did not take place. Instead, in 1976, a decision was made to redefine, restructure, and re-advertise international research grants, with the ICMR allowed to terminate in 1980. This decision reflected, in part, renewed interest in the White House and HHS in international medical research, and a desire to give more support to a new WHO program of tropical disease research.

It also reflected a determination by the new director of NIAID to halt funding for activities, such as social science research, which were outside the objectives of NIAID.

          The new program, International Collaboration in Infectious Disease Research (ICIDR), is more narrowly confined to infectious disease research and immunology. It emphasizes the six diseases selected by WHO, plus diarrheal diseases. Explicit importance is assigned to building the institutional research capacity of the host country institution, and 70-80% of the funds are to be spent abroad on problems relevant to health status of the local people.

          The ICIDR program was announced in 1975 and applications invited. Of the 14 proposals received, only six were rated average or better, and five were awarded five-year grants. Tulane was the sole survivor of the competition from the ICMR institutions. The University of Maryland project failed the competition but received continued NIH funding for two years because of State Department pressure to avoid closing the program in the midst of a period of diplomatic tension.

          The five successful applicants and their host institutions were:

·            Harvard School of Public Health - Federal University of Bahia, Brazil;

·            Cornell School of Medicine - The Federal University and the University of Brasilia; Bahia, Brazil;

·            Michigan State School of Medicine - Central Laboratory of the Ministry of Health, Khartoum, Sudan;

·            University of Illinois School of Medicine - Chiang Mai University, Thailand;

·            Tulane University School of Public Health and Tropical Medicine - Colciencias, Cali, Colombia, and Institute Francais d’Haiti, Port-au-Prince, Haiti.

          The first cycle of ICIDR awards ended in September 1984. Four of the regional five competed successfully for the second round -- Tulane, Harvard, Michigan State and Cornell. Three new projects were also funded:

·            Yale University - Bogota, Colombia

·            Johns Hopkins University - Lima, Peru

·            Wayne State University - Addis Ababa, Ethiopia.

          In addition to institutional awards, the ICIDR program makes exploratory grants to individual scientists for work in an area. Five grants totaling $277,000 were made in 1980 for work in Mexico, India, Nigeria and two in Brazil. In the second round, grants were made for work in Indonesia, Venezuela, Kenya and Brazil.

          Total funding for ICIDR is about $2.8 million, around the same level as earlier expenditure for ICMR. Each institutional project receives only about half the amount annually that went to the ICMRs.

          ICIDR investigators do not take up residence abroad, generally making visits of four to six months at a time. ICMR investigators were often abroad for two or more years. Training is not a primary objective of the ICIDR program, nor was it of ICMR in the later years. Foreign investigators are allowed travel funds now, but were not under ICMR.

          An informal report to NIH from the Michigan State group in October 1984 describes a vigorous collaborative program, thriving under conditions of political uncertainty.

          Ten Sudanese scientists are full participants in research in the field and frequent visitors for varying periods to MSU. Eight senior MSU scientists and six graduate students and research associates have participated. A number of clinically trained students plan to pursue careers in tropical medicine and infectious diseases, one of whom hopes to do so in the military.

          Research underway includes investigations of genetic and other sources of immunity to malaria, pathologic changes in schistosomiasis, the epidemiology of onchocerciasis (which can cause blindness), and testing of various therapeutics. Research funding supplementary to the ICIDR has been received from various departments of MSU and from several pharmaceutical companies.

          Turning to our comparative framework:

1. Scope of the program

          The ICMR program appeared to extend further along the problem-solving spectrum of international health than the ICIDR program because it included a broader range of investigators, such as social scientists. In practice, this may be an illusion. The social scientists in Cali, for example, followed their own research interests without necessary reference to the diseases of concern to their medical colleagues. Similarly, in Malaysia, the ICMR(T) avoided interdisciplinary research. The UC group sought to support people with outstanding research ideas and plenty of enthusiasm, rather than to find people to fit predetermined slots in existing research projects.

          Investigator freedom to define the research task is of course the hallmark of the sponsoring agency, NIH. The annual site visits to the ICMRs arranged by NIH were considered by staff to be a rather unusual intrusion into the affairs of grantees, made necessary perhaps by the breadth and complexity of the enterprises. They were also a major factor in helping the individual field directors maintain quality and phase out programs and individuals who were unproductive.

          The stronger the program, the more the visits were appreciated. The ICMR committee was remarkably stable, competent, and dedicated, and the annual site visits and meetings in the U.S. with host institution principal investigators were a major factor in the relative success and longevity of the program.

          It would be unfair to criticize the ICMR program for not being a tightly knit, targeted attack on a tropical disease when that was not its stated purpose. It is legitimate to question, however, whether the approach favored by NIH and the university community would be the most effective way to use limited funds if the purpose were to reduce the disease burden on people who live in the tropics. Perhaps the optimal pattern of organization for stimulating new discoveries and for training outstanding researchers is not ideal for carrying the scientific process to the point where people directly benefit from it.

2. Degree of Collaboration

          Close collaboration with host-country scientists was possible under the ICMR, as we have seen in Cali and Kuala Lumpur, but it was not universally achieved, nor was it required under the terms of the grant. In some circumstances, such as Lahore, it may not have been possible, given the level of local medical institutions. The ICIDR program, reflecting changes in the international climate perhaps, or heightened NIH sensitivity, is meant to be highly collaborative.

          Curiously, the two ICMRTs that achieved the closest collaboration with host country institutions, Cali and Kuala Lumpur, were both led in their early years by British expatriates.

3. Results: Impact on Diseases

          In the absence of an evaluation of the ICMR program, it is difficult to determine the contribution it made to understanding and controlling tropical disease. We saw in the Cholera story that the Johns Hopkins group in Calcutta made significant contributions to understanding cholera and diagnosing E. coli and shigella. They also contributed to the development of oral rehydration therapy. Other ICMRs may have made similarly vital contributions.

          In general, however, as Laska put it, the programs were designed to advance scientific knowledge and train researchers, rather than to have an impact on the course of a disease in an area.

4. Results: Capacity Building

          The ICMR program was explicitly designed to provide in American medicine a small core of competence in exotic diseases. Seal argued that the increase in capacity of American institutions sought through the program did not occur, largely because tenured positions could not be offered. It’s an important point, if valid, but the evidence is not available to confirm or refute it. Dunn cites a dozen former participants in the program who are continuing their involvement in international health at UC San Francisco and nearby institutions. Tropical medicine is very strong at UCSF due to the ICMR program. The reasons UCSF did not compete successfully for the ICIDR program have more to do with the fact that many researchers are not interested in infectious diseases, some are interested in other parts of the world, and the jungle dengue project had reached a logical stopping point by 1980.

          Despite this explanation, the lack of success of three of the four universities with ICMRs in competing for ICIDR grants is perplexing, given their advantages in field experience. Possibly it is difficult to sustain an interest in tropical diseases in a university setting.

          One indication that this was so is that the universities often had to reach outside their faculty ranks in order to staff their overseas centers. Even those scientists with long-term interest in tropical diseases did not wish to stay abroad for many of the 20 years of the program. It was professionally costly to be out of the mainstream of American science for too long, often working in poorly equipped laboratories. It was also disruptive of the teaching programs for senior people to spend too much time away, even on university business.

          The results of the ICMR program in terms of institutional capacity building seem therefore to be disappointing. In manpower terms, the ICMRs may well have been a success. They provided abundant opportunities for relatively large numbers of scientists to gain experience in tropical disease research, but they didn’t provide career inducements to keep them engaged for the balance of their careers.