The 74th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on June 5, 1997. NIH Director, Dr. Harold Varmus, began by summarizing several personnel matters. He also provided an update of developments affecting the NIH budget, for which the President requested a 2.5 percent increase above the FY 1997 level to $13.1 billion for FY 1998. Although the House-Senate budget resolution does not significantly increase the NIH budget beyond that 2.5 percent, a non-binding sense-of-the Senate resolution calls for the NIH budget to double during the next five years.
Dr. Varmus described several recent developments involving training of clinical research investigators, including: (1) the planned arrival this summer of medical students to train in the Intramural Program at NIH; and (2) talks with industry about training needs in specific specialties. He also described several changes relevant to efforts to bolster the NIH Clinical Center programs. In addition, he reported that the controversial study for evaluating the impact of a needle exchange program on the transmission of HIV among drug users, which the ACD provided advice about in December 1996, was subsequently revised, and is now underway in Alaska.
Dr. Varmus summarized his participation in several Congressional hearings, including some that dealt with the issue of mammalian cloning and others that dealt with research priority setting. Within NIH, review criteria for research grants are being refined, study sections reorganized, and a comprehensive review of long serving Institute Directors as well as a number of Institute Intramural Programs is under way. He also mentioned highlights of several research projects being carried out in the Intramural program.
Dr. John La Montagne, Director of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), described the impact of malaria on human health worldwide. He also outlined plans to exploit new opportunities for studying this disease that may lead to new ways of combating and preventing it.
Dr. David Baltimore of the Massachusetts Institute of Technology, who chairs the NIH AIDS Vaccine Advisory Committee, described stepped-up efforts to develop a safe and effective vaccine for preventing this disease. With the cooperation of NIAID, this Committee established an innovative grants program that is focusing initially on improved animal models for developing and testing AIDS vaccines, HIV envelope protein structure, and antigen presentation. He said that the overriding problem facing vaccine researchers is identifying and overcoming the detrimental changes that occur when HIV strains are adapted to grow in laboratory culture systems, thus changing their usefulness produce vaccines.
Dr. William Paul, Director of the Office of AIDS Research (OAR), described plans for a new intramural AIDS Vaccine Research Center with, at least, limited manufacturing capacity. Emphasizing that these intramural efforts will not be done at the expense of extramural AIDS vaccine research programs, he said that $10 million was allocated for Center activities, mainly from NIAID and the National Cancer Institute (NCI), and that additional resources within the OAR budget could be made available.
Dr. John Coffin of Tufts University Medical School recently agreed to develop a program to study drug resistance of HIV at the NCI research center in Frederick, MD. The new program will have its own advisory committee, recruit investigators to work on the problem, and support extramural researchers through contract and grant mechanisms. Plans call for the new program to sponsor studies in several areas, including structural biology and biochemistry, mechanisms of drug action and drug resistance, molecular virology and genetics, clinical virology, epidemiology, and animal models.
Committee members commented on the near-final draft of a booklet describing the complex system used by NIH for setting research priorities. Several Committee members stated that the booklet is well written and contains useful information, but expressed concern that it may make the priority setting process appear too smooth and more static than it really is. Committee members also suggested that the draft include information about how special research needs are recognized and met and the need for research projects sometimes to focus on very speculative problems.
Dr. Marvin Cassman, Director of the National Institute of General Medical Sciences (NIGMS), described the efforts of a working group to analyze the experiences of young researchers in the extramural community, during the period 1980-1985, as they moved into positions as independent investigators. Based on their analysis, the members of this working group recommended that the First Independent Research Support and Transition (FIRST) (R29) research award mechanism be discontinued, but that the regular research grant application (R01) be modified so as to indicate clearly those proposals submitted by first-time applicants. They further recommended that the standard award period for the R01 grant be extended to five years for new investigators and that the number of awards given to new investigators balance that of investigators leaving the grant system.
Dr. J. Richard McIntosh of the University of Colorado, who serves on a committee of the National Research Council (NRC) Board on Biology, outlined a nearly completed NRC report on the demographics of individuals receiving Ph.D. degrees in biology. Although about 7,300 individuals now receive such a degree each year, the number of PhD. biologists who are employed in their scientific areas seems to be leveling off. Because of the recent influx of PhD. biologists who are foreign nationals, the rate of supply is about two-fold greater than the number of jobs. Dr. McIntosh said that, if this trend continues, biology no longer may attract as many qualified young people to pursue research careers as it has in the past.
Dr. Harold Varmus, Director of the National Institutes of Health (N1H), began the 74th meeting of the Advisory Committee to the Director (ACD) by summarizing several personnel makers. He first introduced the most recent member to join the Committee, Mr. Norman Francis, President of Xavier University, New Orleans, Louisiana, and then reminded ACD members that Dr. Elvera Ehrenfeld had assumed her duties as director of the Division of Research Grants (DRG) in January. He also acknowledged the services of Dr. Ruby Hearn and Dr. Joshua Lederberg, who are retiring from ACD, as well as those of Dr. James Snow, the Director of the National Institute on Deafness and Other Communications Disorders, who is retiring from NIH in September. Dr. Varmus told committee members of progress in the search for a Chief Information Officer and a Director for the new Vaccine Laboratory at NIH, and announced the recent appointment of Dr. John Eisenberg from Georgetown University Medical School as Administrator for the Agency for Health Care Policy and Research, DHHS.
Dr. Varmus provided Committee members with an update of developments affecting the NIH budget, for which the President requested a 2.5 percent increase above the FY 1997 level to $13.1 billion for FY 1998. Dr. Varmus and other senior NIH officials provided testimony in extended hearings before the House of Representatives Appropriations Subcommittee on Health and Human Services, Labor and Education, which is chaired by Representative John Porter (R-IL). Additional hearings, using a multi-panel format, before the Senate Appropriations Subcommittee on Labor, Health and Human Services, and Education, which is chaired by Senator Arlen Specter (R-PA), had been rescheduled for June 11.
At present, the House-Senate budget resolution appears to make it unlikely that the NIH budget will increase much beyond the President's request. However, a non-binding sense-of-the-Senate resolution, introduced by Senator Connie Mack (R-FL) and Senator Diane Feinstein (D-CA), calls for the NIH budget to double during the next five years. Another amendment to the Senate bill, calling for an immediate 7.5 percent increase of the NIH budget, was tabled.
In response to a request from Representative Porter for NIH to review the efficiency of its administrative structure, Dr. Varmus invited Mr. John Mahoney, former Deputy Director for Administration, NIH, to oversee a study, which will be conducted by Arthur Andersen and Company. The study goal is to identify ways by which NIH could save on administrative costs. The study will involve a review of finance, procurement, management, personnel, and buildings and services practices, as well as other administrative makers. A preliminary report is expected in the summer and a final report by October, with a presentation at the ACD meeting in December.
Dr. Varmus also described several recent developments involving the training of clinical research investigators. This summer, medical students will begin to arrive as part of a new clinical research training effort within the NIH Intramural Program, one that is coordinated with a similar Howard Hughes Medical Institute program, for training in basic research disciplines. In a separate development, Dr. Varmus met with representatives of biotechnology and pharmaceutical firms, who described their interest in the training of clinical researchers versed in specialties, such as pharmacology, and in the development of better approaches to clinical trials for the evaluation of new drugs and other therapeutic products. From these discussions, preliminary plans emerged to hold a joint forum with industry this fall to deliberate further these and related issues.
The recently established NIH Clinical Center Board of Governors has approved the Center's strategic plan, and a Board subcommittee is reviewing options for providing more stable funding for the Center and creating incentives for its wider use. The first Clinical Research Day, held February 10, was so successful that it will likely become an annual event. The ground breaking for the new Hatfield Clinical Research Center (CRC) is scheduled for this fall. Ninety million dollars is budgeted in FY 1998, an additional $90 million in FY 1999, and $40 million for FY 2000 for construction of the CRC. Recent appointments to the Clinical Center include Dr. Nicholas Bryant, to direct radiological imaging sciences, and Dr. Ezekiel Emmanuel to direct clinical bioethics.
During the ACD meeting last December, Committee members discussed a research proposal then before the National Institute on Drug Abuse (NIDA) to evaluate the impact of needle exchange on transmission of HIV. The proposal drew criticism from the organization, Public Citizen. Ethics Issues were subsequently reevaluated by a panel chaired by Dr. Robert Levine of Yale University. The Levine panel concluded that the proposed study meets ethical criteria and should go forward. In conveying the panel's report to NIDA, Dr. Varmus also recommended, in keeping with a request from the ACD, that the Institute provide funds covering the costs for all study subjects to be vaccinated against hepatitis B. In addition to vouchers for vaccinations, vouchers covering the costs of taxis are being provided to facilitate subject access to needles at pharmacies. Changes in the protocol now exclude subjects who are former drug injectors and expand the numbers of active users to be recruited. The study began in Alaska in May.
Recently, President Clinton has referred to, with increased frequency, activities and programs involving NIH, including AIDS vaccine efforts, research programs related to early childhood and development, and career development awards for young NIH-sponsored investigators. In addition, a variety of notable figures have recently visited the NIH campus, including the actor Christopher Reeve, who testified before Congress about NIH funding, particularly in the neurosciences; Dr. Ian Wilmut, who presented a seminar on his research on cloning of sheep before overflowing crowds; Representative Michael Bilirakis (R-FL), Chairman of the House of Representatives Commerce Subcommittee on Health and the Environment, along with other members of the Subcommittee, who will deliberate the bill reauthorizing NIH programs; and many House staff members.
Dr. Wilmut's February announcement that he had cloned an adult sheep stirred a great deal of interest at the Federal level, prompting President Clinton to impose a moratorium on any federally funded human cloning research and to ask the National Bioethics Advisory Commission (NBAC) to review this issue and complete a report within 90 days. (This report was made public in early June, shortly after the ACD meeting.) Cloning also became a major topic during several Congressional hearings, including one involving NIH appropriations, another before the House Biotechnology Subcommittee, which is chaired by Representative Connie Morella (R-MD), and yet another before the Senate Subcommittee on Public Health and Safety, which is chaired by Senator William Frist (R-TN).
In other hearings before the House Subcommittee on Human Resources of the Government Reform and Oversight Committee, chaired by Representative Christopher Shays (R-CT), Dr. Varmus reviewed the operations of the NIH Office for the Protection from Research Risks, which oversees local institutional review boards. He discussed the process for obtaining informed consent from participants in clinical trials, with specific reference to studies of HIV transmission between mothers and newborn children, and other studies of patients with neurodegenerative diseases or mental illnesses.
In other Congressional hearings, including some that are pending, Dr. Varmus discussed or will consider priority seeing for research, with an emphasis on identifying priorities related to different diseases. Based on these discussions, Dr. Varmus and Dr. Philip Gorden, Director of the National Institute of Diabetes and Digestive and Kidney Diseases, arranged a workshop for September 4 and 5, 1997, to survey assess the state of diabetes research.
Dr. Varmus is engaged in discussions with industry representatives, with leaders of the National Academy of Sciences (NAS), and with legal experts, including ACD member Ms. Rebecca Eisenberg and Mr. John Batten of Stanford University School of Law, on the topic of intellectual property and easing restrictions on access to new research materials and methods. The ability to use such materials freely can accelerate scientific progress and more rapidly bring forth biomedical products to improve public health. Ms. Eisenberg will chair a subcommittee of the ACD to deal with these issues.
To improve peer review of grant proposals, Dr. Ehrenfeld is reorganizing study sections within DRG, starting with an integration of those study sections housed in the former Alcohol, Drug Abuse, and Mental Health Administration, that review grant proposals in the neurosciences.
In a related development, Dr. Varmus recently announced, before the Peer Review Oversight Group, the five criteria that are now to be used in evaluating research proposals. They are: (1) study significance, whether the proposal addresses an important problem; (2) the planned approach, whether the methods and designs are appropriate; (3) innovation, whether there are novel concepts and aims; (4) the quality of the investigator, whether he or she is properly trained and has appropriate experience; and (5) quality of the scientific environment and any collaborative efforts being planned. These criteria are to be applied flexibly, and the rating for each proposal is to be a single, rather than a five-part, score. These augmented criteria also should help applicants when preparing their research proposals, according to Dr. Varmus.
At the administrative level within NIH, a comprehensive review of Institute Directors is now under way, starting with those who have served longest. Conducted in confidence and usually involving representatives from the wider biomedical research community, these reviews will provide Directors with guidance and suggestions that may not reach them through ordinary channels. In a similar vein, an Institute-by-Institute review of the Intramural Program (IP) continues in response to one of the recommendations from the committee, which was chaired by Paul Marks of Memorial Sloan-Kettering Cancer Center and Gail Cassell of the University of Alabama, that evaluated the IP in 1994.
Dr. Varmus noted several highlights from research programs within the IP, including a new technique for color-coding each of the human chromosomes; a NMR-based technique for visualizing occlusion within coronary arteries; a multi-Institute team's successful cloning of the gene that apparently is responsible for the multiple endocrine neoplasia 1 syndrome; completion of high-resolution maps for human chromosomes 7 and X; a study showing the efficacy of implantable defibrillators in patients with coronary disease; and another study showing that aggressive lowering of blood cholesterol benefits those who have had coronary bypass surgery.
The National Foundation for Biomedical Research is soon to become the Foundation for the NIH. The Foundation is chaired by Charles Sanders of the Europa Center and many other distinguished individuals have agreed to serve on the Board. The appointment of an executive director will be announced shortly.
In response to questions about changing the research grant application forms to reflect the recent changes in the review criteria by which such proposals are now to be judged, Dr. Wendy Baldwin, Deputy Director for Extramural Research, indicated that only minor format changes are being considered. More comprehensive changes to the written application forms, however, may be made to accompany the introduction, within the next two years, of an alternative, electronic format for research grant applications.
Dr. Elaine Fuchs suggested that grant application forms be changed to emphasize that NIH grantees be willing, by the time they publish their findings, to share the scientific reagents and methods they have developed, a policy that some but not all scientific journals also endorse. Dr. Baldwin noted that a statement describing the NIH policy on sharing reagents and methods does appear in grants guidance documents.
In responding to questions from Dr. Philip Needleman about apparent differences between peer review procedures affecting extramural and intramural research programs, Dr. Varmus pointed out that peer review of the IP tends to look broadly on past programs and overall accomplishments of investigators, whereas reviews of grant applications tend to focus more narrowly on an extramural investigator's immediate research plans. Dr. Needleman suggested that the former approach also may be suited to reviews of extramural center grants and program projects.
Report on Malaria Research
Dr. John La Montagne, Director of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), described the impact of malaria on human health worldwide and in the United States, summarized NIH-sponsored research efforts on this disease, and outlined some of the opportunities for studying this disease that may lead to new ways of combating and preventing it.
A child dies from malaria every 20 seconds, at least 2.3 billion people are at risk for this disease, 300-500 million people are infected with the parasite responsible for causing some 120 million cases, and at least 1.5-3 million deaths occur each year from this disease (counting only those that are recorded in health care facilities), according to Dr. La Montagne. There are no effective vaccines for preventing malaria, and resistance to the antimalarial drug chloroquine is already widespread and growing, particularly for the severe form of disease caused by Plasmodium falciparum. Anopheles mosquitoes that serve as the vectors for this parasite are also becoming increasingly resistant to insecticides, and other measures for controlling the vector, such as using insecticide-impregnated bed netting, no longer appear to hold long-term promise.
Not only does malaria present an enormous public health and economic global burden, it also threatens U.S. citizens who travel abroad, and there is a growing risk that it might reestablish itself in certain vulnerable regions of the country. Some 3,000 cases are reported each year in the U.S., and the 10 million travelers who enter and pass through the country as well as the 23 million Americans who travel to endemic regions each year greatly increase the risk of the infection rate sharply increasing. The disease and the parasite that causes it represent an important scientific and public health challenge, with many open questions about every aspect from its epidemiology to details about the multi-stage life cycle of the parasite.
Despite these inviting possibilities, pharmaceutical companies are not particularly active in studying malaria or developing new means for treating it. Most malaria research is conducted in the public sector. Annual research expenditures from NIAID amount to $19 million, which is about one-fourth of total global spending on malaria research, with the Department of Defense, the U.S. Agency for International Development (AID), the Wellcome Trust, and the World Health Organization (WHO) accounting for most of the remainder.
Although lately U.S. AID funding for malaria research has substantially decreased, NIH and specifically NIAID investments in such research are increasing. NIAID Director Dr. Anthony Fauci said that the Institute identified malaria research as fitting with other priorities among emerging and reemerging infectious agents several years ago. Thus, the Institute recently formulated a 10-year plan for developing a vaccine and, in doing so, identified infrastructure and reagent needs to implement at an early stage, if that long-term goal is to be realized. However, because overall growth of the NIH budget is modest, a rapid increase of new funds for malaria research is not expected.
Dr. La Montagne stated that, although most NIAID-supported malaria research is fundamental, investigator-initiated, a portion of the solicited effort is intended to sustain a system within the extramural community for evaluating potential treatments and vaccines. Several of those programs involve collaborative efforts between U.S. academic institutions and their counterparts in tropical regions, such as in Kenya, Malawi, Cameroon, and Mali, where malaria is endemic. These research programs are also fortified through collaborations with the National Library of Medicine, which has helped to establish Internet access for investigators in Africa, and with the Fogarty International Center, which helps to organize key conferences, such as the major international conference on malaria held in January 1997 in Dakar, Senegal, and for planning a follow-up conference to be held in the Hague in July 1997.
Current research efforts point to several promising therapeutic candidates, such as inhibitors of hemoglobin-specific proteases and chloroquine analogs and antagonists of other parasite metabolic pathways, as well as exciting prospects for developing vaccines. Several vaccine strategies are being actively pursued, including development of candidates intended to block the parasites when mosquitoes inject them into the blood and other candidates that use blood-state antigens of the parasite to prevent it from becoming established in the liver. Some combination of these and other approaches may prove effective, according to Dr. La Montagne.
An international research consortium, with teams at the Sanger Centre in the U.K., at Stanford University, and at several other sites including NIH near Washington, D.C., is beginning to map and sequence the genome of Plasmodium falciparum, which contains 30 megabases of DNA on 14 chromosomes. Such information is expected to provide additional targets for the development of therapeutic products. This project is principally funded by NIH, the Department of Defense, the Wellcome Trust, and the Burroughs-Wellcome Fund.
The participants at the Dakar conference made a series of recommendations about malaria research, calling for improved communication within the international community of malaria researchers and clinical investigators; the establishment of networks of scientists interested in similar malaria-related topics; the provision of common reagents to multi-center malaria research teams; improvements in training and career opportunities, particularly for investigators in the developing world; and the pooling of resources to support malaria research. Several options being considered for this latter recommendation include: (1) forming a single pool of resources for worldwide malaria research efforts; (2) establishing a common application and review process while funding projects through separate agencies in a process that would identify potential collaborations at an early stage; and (3) maintaining the current system.
Commenting on the report from the Dakar conference, Dr. Fuchs pointed out that not only is it important to focus on malaria as a disease, but also to recognize that local economic and technology factors in endemic areas also greatly affect the epidemiology of this disease and strategies for combating it. Moreover, she suggested that developing countries may resent what they see as a lack of commitment by industrialized nations to address the immediate public health and underlying problems associated with malaria. Dr. La Montagne stated that officials from WHO and from African nations see the solution to these challenges as necessarily involving local participation, especially by their own biomedical research and health care experts, who want to enter into "genuine" collaborations with their counterparts from industrialized nations. Dr. Varmus said that, in addition to concrete research benefits from collaborating with investigators in countries where malaria is endemic, malaria research also provides a prototype for modeling collaborative efforts to meet other international biomedical challenges.
Dr. Marc Kirschner commented on the difficulties facing NIAID if, during a period of little or modest overall budget growth, a decision were made to increase malaria spending at the expense of investments in research on other infectious diseases. He also pointed out that U.S. medical and graduate students are not being taught much about malaria and other parasitic diseases. Dr. Fauci said that, because malaria is such an enormous worldwide public health problem, moderate increases in resources are warranted. Moreover, new scientific opportunities to collaborate with African colleagues further justify increasing investments in this research area. Dr. Varmus added that medical schools should be encouraged to move the teaching of subjects such as malaria from specialized courses in tropical medicine into the general curriculum.
Dr. Jane Menken suggested that perhaps collaborations with developing countries should begin by establishing simple measures against malaria before taking on sophisticated or highly technical research programs. Dr. La Montagne said that local infrastructure-building efforts, some supported by agencies such as the World Bank, are under way. With some inane already in place and new scientific opportunities ready to be pursued, it seems appropriate to continue building on the momentum that was evident in Dakar.
Dr. Larry Smarr asked whether there are efforts to model malaria systematically, commensurate with its enormous complexity as a disease involving several stages of parasite, a mammalian host, an insect vector, and an ecosystem that enables these entities to interact. Dr. Varmus agreed that computer modeling could be useful for identifying points of vulnerability in the malaria disease cycle. Dr. La Montagne said that, although improvements in living standards will certainly help in overcoming malaria, other simple but effective measures, such as vaccines, low-cost drugs, and safe insecticides, undoubtedly also will be needed.
In referring to research on various proteases and protease inhibitors, Dr. Needleman said that established or contemplated malaria research consortia might provide opportunities for industry to contribute to progress in combating this disease, perhaps by reexamining proprietary chemical entities and related information that companies may have produced in efforts to develop entirely different products. He said that systematic screening with robotics could be used to reevaluate high numbers of such synthetic chemicals.
Report on AIDS Activities
AIDS Vaccine Research Committee/Dr. David Baltimore
Dr. David Baltimore of the Massachusetts Institute of Technology chairs the NIH AIDS Vaccine Advisory Committee (AVAC). In pointing to broad similarities between AIDS and malaria, Dr. Baltimore said that AIDS now ranks with malaria and tuberculosis as a very deadly, growing public health problem throughout the world. Because of the dimensions of the problem and the high cost of therapeutic drugs for treating AIDS patients, the development of a safe and effective preventive vaccine is essential, as it has been for many other viral diseases.
The current U.S. AIDS vaccine development program has two main components, one in industry and the other in the public and academic sectors. Industry has pursued three main goals: (1) production of HIV laboratory strain-based, antibody-inducing candidate vaccines for clinical testing; (2) development of HIV-encoding, DNA-based vaccine candidates in viral vectors or as naked DNA that are intended to induce cytotoxic T lymphocytes (CTLs); and (3) more general efforts to develop better materials, including vectors, vaccines based on nonlaboratory HIV strains, and improved adjuvants.
The Government sector has established an extensive network for clinically testing and evaluating candidate vaccines, with most tests so far being Phase I safety and immunogenicity tests. A major Phase II clinical trial is beginning to evaluate a prime-boost strategy, which uses a canarypox vector to prime the immune system followed by boosts with a HIV-derived protein immunogen, with both components based on laboratory strains of HIV. Because the response rate is about 20 percent (with an aggregate response of as high as 40 percent), this strategy may be further tested in a Phase III clinical trial.
Other components of the Government-sponsored AIDS vaccine research program are fragmented and need improved oversight and coordination, according to Dr. Baltimore.
In addition to Dr. Baltimore, the NIH AVAC consists of a diverse group of experts who are mandated to advise NIH about improving its vaccine research program. The Committee is holding a series of workshops inviting outside experts, including researchers based outside the U.S., to share fresh insights about AIDS. With the cooperation of NIAID, the Committee also established an innovative grants program early in 1997 that encourages researchers to focus on specific problems in vaccine research, with the main issues identified for the first round of applications being animal models, HIV envelope protein structure, and antigen presentation as a key step in inducing CTL responses.
The Committee has identified several additional challenges facing investigators who are developing AIDS vaccines, according to Dr. Baltimore. Perhaps the overriding problem is identifying overcoming what happens when REV strains adapt to growth in laboratory culture systems, an adaptation that alters key antigenic HIV envelope glycoproteins in ways that are detrimental to their use in vaccines.
In large part because vaccine development takes so many years, the first round of vaccine clinical trials undertaken with candidate products based on laboratory-adapted HIV strains moved ahead despite a growing recognition that those vaccines need to be drastically revamped. Yet, because each phase of development, production, and testing of a vaccine is very expensive, h is important to gain maximum information from these clinical trials, even when they are based on ultimately ineffective products. There is no obvious or simple way to reduce the time needed for basic vaccine development, according to Dr. Baltimore.
Dr. Baltimore also said that old, discarded concepts about AIDS vaccines, including the idea of developing a killed virus vaccine, need to be carefully reexamined. Other possibilities include virus-like particle-based peptide and protein, and better DNA vaccines. Because a live, attenuated version of SIV works as a vaccine in preventing AIDS-like syndrome in macaques, this approach for making a vaccine against AIDS also needs to be carefully reexamined. Australian researchers are considering a Phase I test of this concept.
NCI AIDS Vaccine Research Center/Dr. William Paul
NIAID and the National Cancer Institute (NCI) will jointly provide the resources and leadership for an intramural AIDS Vaccine Research Center, which eventually will be housed in its own facility and will have at least limited manufacturing capacity. Before that move, a NIAID-NCI steering committee plans to assemble an intramural team of investigators, who will meet regularly to discuss scientific issues and identify specific goals. In addition, a resource allocation committee will review proposals and will assess what additional funds may be needed for pilot production of candidate vaccines, animal testing, clinical trials, and other activities of the new Center.
Dr. William Paul, Director of the Office of AIDS Research (OAR), said that an important challenge facing the new Center will be to bring immunologists and virologists together in close working relationships and to reinvent the science of "vaccinology. " Emphasizing that these intramural efforts will not be done at the expense of extramural AIDS vaccine research programs, he said that $10 million was allocated for Center activities and that additional resources within OAR budget would be made available if necessary.
Dr. Paul pointed out that, between FY 1994 and FY 1998, the number of AIDS research project grants has increased by more than 50 percent. Moreover, during the past two years, the NIH budget for overall AIDS research has increased by about 9.2 percent, while that for AIDS vaccine research has increased by more than 33 percent. These increases provide sufficient flexibility to support these expanding AIDS vaccine research efforts, in keeping with recommendations made by the AIDS Research Review Committee, which was chaired by Dr. Arnold Levine of Princeton University.
NCI Program in HIV Drug Resistance
Dr. John Coffin of Tufts University Medical School recently agreed to develop a program studying HIV drug resistance at the NCI research center in Frederick, MD). The new program, under the NCI Office of the Director, will have its own advisory committee, will recruit investigators to work within the program, and support extramural researchers through contract and grant mechanisms.
Dr. Coffin said that current multiple antiviral drug strategies for treating HIV-infected individuals provide a proof of concept that inhibiting the virus can suppress disease symptoms for extended periods. Some patients, however, fail to respond to such treatments and many more eventually fail treatment because drug-resistant HIV variants overcome the short- and mid-term effects of every single and multiple drug combination that has been tested.
Resistance to antiviral drugs, including nucleoside and non-nucleoside reverse transcriptase inhibitors (RTs) as well as the newer protease inhibitors (PIs), reflects the high mutation rate of HIV. Dr. Coffin said that the mutation rate, in turn, reflects the extraordinary dynamics of REV growth within infected individuals. Because considerable viral replication occurs before a patient ever begins antiviral therapy, genetic variants capable of drug resistance already are embedded in the HIV reservoir within that individual. Due to limitations in the sensitivity of virus detection methods, even when triple-drug therapy seems to suppress HIV completely, perhaps more than one million cells within the individual being treated still carry HIV.
Dr. Coffin said that the new NCI program will include studies in structural biology and biochemistry, mechanisms of drug action and drug resistance, molecular virology and genetics, clinical virology, epidemiology, including questions of whether drug-resistant HIV is transmissible, and animal model studies. Another objective of the program is to develop refined statistical models for predicting how initial REV levels and mutation rates in infected individuals may affect the outcome of different drug treatment regimens. Still other objectives include whether anti-resistance can somehow be incorporated into antiviral drug design, whether resistance can be detected at very low levels in patients, and determining whether there is a viral- load threshold below which infected individuals no longer transmit the virus to others.
Dr. Smarr asked whether drugs could be designed to adapt dynamically to changes that may occur in the HIV molecular target. Similarly, Dr. Needleman suggested that pro- and prepro-drugs be designed that would be biochemically altered and activated in such a way as to delay or preclude the development of resistance. Dr. Coffin replied that an important goal of the program is to determine what the limits of mutability may be in any particular HIV drug target. Virus population studies would entail determining the size of the evolutionary space REV can occupy.
Dr. Kirschner asked whether novel methods for identifying key antigenic sequences of HIV are under development. In response, Dr. Baltimore said that important insights are coming from the realization that natural V strains use a different host cell co-receptor to infect and replicate within cells than do laboratory-adapted strains. With such information, it becomes possible to grow and more fully investigate such natural HIV strains. Dr. Baltimore added that preliminary findings indicate that few monoclonal antibodies neutralize antigens from such strains.
Report on Priority Setting
Dr. Varmus provided ACD members with copies of a near-final draft of a booklet describing how research priorities are set and of testimony he delivered before the Senate Subcommittee on Public Health and Safety, which is chaired by Senator William Frist (R-TN). He asked ACD members to comment on whether the information about priority setting was presented clearly and also on whether priorities are being set in an appropriate fashion at NIH.
Dr. Steven Katz, Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said that NIH was asked by the Congress to consider the full array of relevant criteria NIH uses to construct its research portfolio. Ms. Anne Thomas, Director of the NIH Office of Communications, explained that a wide array of NIH leaders participated in preparing and revising drafts of the priority setting booklet. The draft booklet describes a stable but complex system for setting research priorities that is responsive to the advice provided by a wide variety of communities.
Coincidentally, while NIH was drafting the priority setting handbook, officials at the NCI were gathering, information, through focus groups held in four U.S. cities, about what the public knows about biomedical science, how research is done, and what people think about these activities. Three sets of people were surveyed: (1) community leaders, (2) individuals with a keen interest in health research, and (3) individuals whose lives were affected by cancer.
Ms. Thomas said that, although people who had been surveyed seem well aware that resources for doing research are limited, they had little idea as to how those resources are distributed. Insights from the focus groups helped those drafting the priority setting booklet recognize some of the misconceptions among the general public that need correcting. The booklet also is intended to provide useful information to members of Congress and their staffs.
Ms. Thomas said that the drafting committee chose to present the research priority setting process in a straightforward, factual, and jargon-free manner, without minimizing the complexity of the process or inserting self-serving commentary. The document includes examples and several charts to liven the text, and it has been provided in draft form to several Congressional committees, the Ad Hoc Group for Medical Research Funding, and other professional and research organizations. In response to comments received, some changes are being contemplated, including the addition of an executive summary.
Dr. Katz said that the draft booklet describes how science works as a multidisciplinary enterprise and, despite limited similarities, how it differs from business and other undertakings. The booklet indicates that, although the progress of science is somewhat unpredictable, it is not purely random because it is self-correcting and also is subjected to wide public scrutiny. A section of the document describes key elements in NIH history, including the establishment of individual institutes, the Clinical Center, the extramural program, and the importance of training to the research mission.
Other sections also describe how resources for different kinds of research are distributed, how those resources are put to use, the variety of mechanisms used to distribute NIH resources, and the time frames that come into play when making such decisions. Part of the decision-making entails assessments of the impact on public health by the broad array of diseases, the ever-changing opportunities for doing something specific about any one of those diseases, and choices about basic or more applied or clinical approaches to take in addressing specific diseases. Amid these efforts, peer review represents the research community's commitment to recognize scientific excellence among the many proposals that are submitted each year for funding.
Still other sections of the draft document describe the types of people and the many organizations within and outside NIH that have a role in research priority setting. Administratively, the NIH Director, Institute Directors, and other staff members at NIH bring a rich and varied scientific background to their duties. Many outside advisory committees and councils from the research community serve integral roles in setting priorities, and there is steady input from Congress, the Administration, patient advocacy groups, and from individuals. In addition to the standard mechanisms for stimulating research in newly identified areas, the NIH Director has discretionary funds, a one percent special transfer mechanism, and the Shannon awards to prompt research activity in selected fields.
Dr. Kirschner said that the draft booklet is well written and contains a great deal of useful information about priority setting. He also noted that it may make the priority setting process appear too smooth and more static than it really is. He suggested that the booklet should more fully reflect the advantages and disadvantages of the NIH being organized into categorical institutes, but recommended against including a question-and-answer section.
Dr. Jane Henney recommended that special care be taken with the wording of the section describing how the NIH Intramural Program is reviewed. She also suggested the document reflect the fact that although a wide variety of advisory comments help to shape NIH priorities, they are not given equal weight. Dr. Ezra Davidson agreed, noting AIDS as an example of a community that forcefully helped to make research on this disease a high national priority. He also said that the document, while outstanding, is too long and complex.
Dr. Needleman recommended that the document describe the NIH commitment to support some truly adventuresome research within its overall portfolio. Dr. Smarr said that, because peer review tends to favor incremental rather than adventuresome research, the document should draw attention to the importance of discretionary funds in adjusting this balance. Dr. Henney noted that when NIH calls for scientific innovation, it does not direct or create scientific opportunities from a central authority. Dr. Varmus said that a sidebar might help to explain how discretionary funds are sometimes used to adjust priorities along the margins when proposals are not funded following peer review and that the wording of the draft booklet could be modified to emphasize how NIH works to "recognize" rather than "create" scientific opportunities.
Dr. Fuchs said that, although the NIH budget is no longer expanding at the rapid rate characteristic of the 1950s and 1960s, the rate of biological discovery is rapidly expanding, causing something of a mismatch. The process is necessarily imperfect, even though NIH does its best to set priorities under these circumstances. Hence, advice from Congress, the scientific community, and the public is essential for redirecting priorities and correcting mismatches.
Biomedical Research Careers
Report on New Investigators/Dr. Marvin Cassman
Dr. Marvin Cassman, Director of the National Institute of General Medical Sciences (NIGMS), described the efforts of a working group to analyze the experiences of young researchers in the extramural community during the period 1980-1985 as they moved into positions as independent investigators. Based on their analysis, the members of this working group recommended that the R29 research award be discontinued, but that the RO1 application be modified to indicate clearly those proposals coming from first-time applicants. They also recommended that the standard period for the RO1 award be extended from four to five years for new investigators. The working group also suggested that the number of awards given to new investigators be set to balance the retirement rate of about 9 percent for investigators leaving the system, and to go higher if the NIH budget growth rate warrants. Even in the absence of any increases, this would result in the same number of awards being made to new investigators as currently occurs.
The working group consisted of officials from NIH including James Onken from NIGMS, who provided much of the data used in the report, and representatives from academic institutions, including John Krystal of Yale University and Trina Schroer from Johns Hopkins University. Because of the period being analyzed, the working group excluded from consideration the research institutes formerly administered under the Alcohol, Drug Abuse, and Mental Health Administration that were incorporated into NIH in 1992.
The members of the working group addressed two main issues: (1) how well have young investigators fared when seeking research support from NIH, and (2) how effective are the NIH funding mechanisms that are intended to benefit young investigators? These questions arose, in part, following a 1994 report from the NAS, suggesting there has been a recent sharp decline in research grant proposals from young investigators.
To address these questions, the working group first examined data comparing numbers of recipients of RO1 grants, the standard NIH mechanism for funding investigator-initiated projects, to those for recipients of R29 (and the predecessor designation, R23, which paid out less money per year than the R29 and did so for three years) grants, which are reserved as first-time only awards for "young" investigators and are funded at no more than $70,000 per year. Although many young investigators shifted from ROls in 1987 and began submitting proposals for the then-new R29s, the total number of proposals from first-time applicants has remained remarkably constant at about 3,000 per year, according to Dr. Cassman. This apparent discrepancy with the earlier NAS report has a simple explanation. NAS looked at investigators who were age 36 or younger, whereas R29s are reserved for first-time investigators. The median age for R29 applicants thus has moved steadily higher since 1987.
The working group members next considered how well first-time investigators compete with seasoned researchers. Despite findings reported in 1996 by a public policy group at the University of California, San Francisco, the NIH historical data indicate only a small difference in success rates between these two groups of investigators. Moreover, there is no relative advantage for obtaining research support from NIH to new investigators who have a Ph.D. versus those with an M.D.
The working group also considered the follow-up success of R29 and R23 recipients compared to investigators who began their careers with RO1 awards, instead of those special one-time-only funding mechanisms. The working group learned that, although these special mechanisms confer an advantage to first time applicants, because their initial success rate is higher than if they competed for RO1 grants, the advantage is transient and, in the longer term, only the better performers in this group tend to become successful grantees as they advance through their research careers.
The working group also looked at how often applicants are being asked to amend and resubmit proposals. For both R29 and RO1 grants, the trend is the same, with steady increases in resubmissions since 1980, when only 10 percent of funded applicants received support on an amended proposal. By 1995, however, at least 50 percent of all applicants had resubmitted their proposals before being faded. Only about 30 percent of new applicants ever apply for R29 awards, meaning the majority of such applicants choose to compete initially against seasoned investigators for RO1 awards, in part, because such grants are more prestigious and provide higher funding levels. Moreover, the overall success rate for first-time RO1 applicants of 37 percent (if averaged over three years rather than considered for a single year) suggests the risk of competing for RO1 support is worth their while, although still less than the probability of receiving an R29 award.
Along with R29 (and R23) awards, the members of the working group also evaluated several other special categories of grant, including theK08 and K11 awards, which are reserved mainly for M.D.s who work with an established mentor, and the R03 award, which enables investigators to generate preliminary data. Although the K08 and K11 awards are meant to draw M.D.s into research careers, the data indicate that numbers of M.D. applicants have remained nearly steady from 1980 to 1995, according to Dr. Cassman. Nonetheless, about 20 percent of those who receive such "K" awards go on to obtain RO1 and R29 awards, which he described as a pretty good success rate. The R03 award receives only limited use by first-time investigators however, and success in obtaining it does not help significantly in later obtaining other forms of research support.
Commenting on the working group's recommendation that R29 awards be discontinued, but that R01 applications be changed to indicate explicitly whether the proposal comes from a first-time investigator, Dr. Needleman said that review panels may not weigh such information enough to encourage young investigators to begin careers in research. Dr. Varmus said that instituting this change in RO1 applications at the same time that the innovation criterion is to be explicitly considered during review might exert unexpected effects on how first time investigators are treated.
Dr. Baldomero Olivera said that preliminary findings should receive less emphasis in proposals from first time applicants, thereby encouraging them to become independent sooner and to pursue higher risk, more innovative projects than they tend to do now. Dr. Varmus said that NIH is no longer asking reviewers to give weight to "feasibility" when evaluating proposals and is seeking a means that will enable postdoctoral fellows to change research topics while still working in a mentor's laboratory as a way of fostering such early independence.
Dr. Menken observed that one reason R29 awardees have a somewhat lower success rate later when applying for RO1 grants is that their initial proposal involved riskier research. On this basis, the R29 category perhaps should be retained because it serves as the equivalent of venture capital.
Dr. Cassman said that some institutions may discourage first-time investigators from applying for R29 awards because of their S70,000 annual cap and because some community membersconsider them less prestigious than RO1s.
Dr. Ting-Kai Li said that such varied attitudes are typical among academic institutions in Indiana, where the $70,000 cap of R29s is unacceptable at the medical school, but works at the University where new faculty are not so dependent on grants for salaries. He questioned whether differences in apparent success rates between recipients of RO1 and R29 grants may actually be greater than the working group's analysis suggests.
Dr. Varmus suggested that the funding cap on R29 awards might be raised, in keeping with a recommendation from the National Research Council Board on Biology. Dr. Ehrenfeld pointed out that increasing funding levels for R29 awards makes them more like ROls. Discontinuing this special category, however, might be a disservice to first-time investigators, whose success rate remains higher for this category of award compared to ROls. She noted that, although the evidence is anecdotal, many community members believe that the R29 mechanism is helpful in fostering newcomers to research.
Dr. Kirschner said that the important goal is to encourage young investigators to do exploratory, high-risk research, regardless of the grant mechanisms in place. Moreover, an important question is why, in light of data indicating a reasonably steady success rate for first-time investigators obtaining support to do research, do so many of them believe that the system is doing so badly. He said that, because other unrecognized factors may be contributing to the gloomy outlook now so prevalent among young investigators, this issue needs to be further examined.
Report on Young Investigators/Dr. J. Richard McIntosh
Dr. J. Richard McIntosh of the University of Colorado has been serving with a committee of the National Research Council (NRC) Board on Biology that is studying the demographics of individuals receiving Ph.D. degrees in biology, using data bases from several sources, including the NRC, the National Science Foundation (NSF), and the Association of American Medical Colleges. He summarized some of the preliminary findings of the committee, whose full report is under review.
Dr. McIntosh said that the number of new Ph.D. biologists expanded rapidly between 1963 and 1970 but then grew more slowly until 1987, when another period of expansion in Ph.D. production began, probably reflecting renewed interests in health care and the successes of the biotechnology industry. Some of that growth also reflects a rise in the number of foreign nationals receiving Ph.D.s in the U.S. An apparent dip in the production rate in 1993 may be attributable to a change in status of Chinese nationals, many of whom converted to U.S. citizenship following the Tiananmen Square episode in China.
Specialty fields within biology may be divided into those in which doing postdoctoral research is common, such as the basic and biomedically oriented fields, and those in which it is not. Dr. McIntosh said that, in general, researchers are spending more time in postdoctoral research positions than they did during the 1970s. Moreover, about 50 percent of postdoctoral researchers across all of biology are foreign nationals.
Although Federal support is especially important for the training of Ph.D. biologists, the NIH component of that investment which is explicitly earmarked for training has not increased during the past decade, according to Dr. McIntosh. Some other NIH sources however, including funds for salaries for graduate assistants on research grants, have increased.
Recently, it has been taking longer for candidates to complete their Ph.D. degree, with the average time across all fields of biology now eight years compared with an average of six years in 1970. This two-year average increase is consistent across all fields, including biochemistry, which now takes an average of six instead of four years to complete a Ph.D. Thus, the average age at which biologists obtain their Ph.D. is 32. Consistent with th is information, the average age of biologists at later stages of their careers has been steadily rising. For example, by 1995 the average age at which Ph.D. biologists receive tenure has increased by eight years, compared with the average age for receiving tenure two decades earlier.
Fewer Ph.D. biologists are pursuing academic research careers than they once did, according to Dr. McIntosh. About a decade ago, 61 percent of Ph.D.s moved into faculty positions at Ph.D.-granting academic institutions, whereas recently that figure has dropped to 38 percent. During the same period, the fraction of biologists going to jobs in industry has doubled, from 12 percent to about 24 percent, with that rate now leveling off.
Dr. McIntosh suggested that, with more biologists spending longer periods doing research at the postdoctoral level, they may be in a holding pattern rather than in training. Nevertheless, their activities at the lab bench are good for science, he said. Whether they are in top-ranked universities or in less prestigious institutions does not greatly affect their next career moves, he added. Only a small proportion, less than 8 percent, is categorized as unemployed or underemployed.
Dr. McIntosh noted that many recent Ph.D. biologists are not doing what they expected to do in their careers, perhaps accounting for the widely held belief that there are problems in biology. Between 1973 and 1993, 3,000 Ph.D. biologists received jobs each year, indicating spectacular increases across the field. During that period, about 5,000 biologists obtained Ph.D.s each year, but that production rate recently rose to 7,300 per year. Meanwhile, the number of employed Ph.D. biologists may be leveling off. Taken together with the recent influx of foreign national Ph.D. biologists, the rate of supply may soon be about two-fold greater than the number of jobs, according to McIntosh. If this trend continues, biology may no longer attract so many qualified young people to pursue research careers.
Dr. Needleman said that industries impact on these demographics is particularly important because the biotechnology industry is no longer rapidly expanding and job opportunities in the pharmaceutical industry are shrinking. Meanwhile, other pressures for the kinds and diversity of training needed within these industries are intensifying.
In response to a question from Mr. Norman Francis, Dr. McIntosh said that very few representatives of minority groups are receiving Ph.D.s in biology, perhaps only 130 of the 7,000 total each year. Mr. Francis said that to increase this number, the challenge would be for majority institutions to increase substantially their training of Ph.D. biologists from minority groups.
Dr. Michael Gottesman, Deputy Director for Intramural Research, suggested that the growing international character of the pharmaceutical and biotechnology industries may help recent Ph.D. biologists who are seeking employment. Dr. McIntosh said that it is virtually impossible to obtain demographic information that addresses international employment trends among Ph.D. level researchers.
Dr. McIntosh also pointed out that several professional and scientific memberships are polling their memberships to determine employment trends and other demographic information.
Summary and Conclusions
The Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) met on June 5, 1997, to consider plans for expanding efforts in malaria research; programs to develop a vaccine against AIDS, plans to establish an AIDS Vaccine Research Center at NIH; a draft of a booklet describing how NIH sets research priorities; a study analyzing how different grant mechanisms affect first-time investigators during their careers and recommendations that derive from that analysis; and a report describing demographic trends for Ph.D. biologists during the past several decades.
The ACD acknowledged and commented on these programs and reports, and recommended that several employment and training issues be further examined.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Ruth L. Kirschstein, M.D., Executive Secretary, Advisory Committee to the Director, NIH
Harold Varmus, M.D. Director, NIH
Table of Acronyms
Advisory Committee to the Director
U. S. Agency for International Development
Acquired Immunodeficiency Syndrome
AIDS Vaccine Advisory Committee
Clinical Research Center
Cytotoxic T Lymphocytes
U. S. Department of Health and Human Services
Division of Research Grants
Human Immunodeficiency Virus
National Academy of Sciences
National Bioethics Advisory Committee
National Cancer Institute
National Institute for Allergy and Infectious Diseases
National Institute on Drug Abuse
National Institute of General Medical Sciences
National Institutes of Health
National Research Council
National Science Foundation
Office of AIDS Research
Reverse Transcriptase Inhibitors
World Health Organization
Appendix A – AGENDA
Welcome and Opening Remarks
Dr. Harold Varmus
Dr. Harold Varmus Dr. John La Montagne
AIDS Activities Vaccine Committee
Dr. David Baltimore
NIH Vaccine Research Center
Dr. Harold Varmus Dr. William Paul Dr. Anthony Fauci Dr. George Vande Woude
Drug Resistance Study
Dr. John Coffin
AIDS Budget and Impact of Initiative
Dr. William Paul
Dr. Stephen Katz Ms. Anne Thomas
Biomedical Research Careers Report on New Investigators
Dr. Marvin Cassman, Dr. Elvera Ehrenfeld
Study on Young Investigators
Dr. J. Richard McIntosh
Intramural Graduate Training
Dr. Michael Gottesman
Appendix B – Advisory Committee to the Director
Harold Varmus, M.D., Chairman Director, National Institutes of Health Bethesda, MD 20892
Ezra C. Davidson, Jr., M.D. Professor and Chairman Department of Obstetrics and Gynecology King/Drew Medical Center Los Angeles, CA 90059
Rebecca S. Eisenberg, J.D. Professor of Law University of Michigan Law School Ann Arbor, MI 48109-1215
Norman C. Francis President Xavier University New Orleans, LA 70125-1098
Elaine V. Fuchs, Ph.D. Amgen Professor of Basic Sciences Department of Molecular Genetics & Cell Biology The University of Chicago Chicago, IL 60637
Ruby P. Hearn, Ph.D. Senior Vice President The Robert Wood Johnson Foundation Princeton, NJ 08543-2316
Jane E. Henney, M.D. Vice President for Health Sciences University of New Mexico Albuquerque, NM 87131
Susan B. Horwitz, Ph.D. Professor Department of Molecular Pharmacology Albert Einstein College of Medicine Bronx, NY 10461
Eric R. Kandel, M.D. Professor Division of Neurobiology and Behavior Columbia University New York, NY 10032-2603
Marc W. Kirschner, Ph.D. Professor and Chair Department of Cell Biology Harvard Medical School Boston, MA 02115
Eric S. Lander, Ph.D. Professor Department of Biology Massachusetts Institute of Technology Whitehead Institute Cambridge, MA 02139
Joshua Lederberg, Ph.D. Professor The Rockefeller University New York, NY 10021-6339
Ting-Kai Li, M.D. Distinguished Professor of Medicine and Biochemistry Indiana University School of Medicine Indianapolis, IN 46202-5124
Jane A. Menken, Ph.D. UPS Foundation Professor in the Social Sciences Population Studies Center and Department of Sociology University of Pennsylvania Philadelphia, PA 19104-6298
Philip Needleman, Ph.D. Senior Vice President Research and Development Monsanto Company St. Louis, MO 63167
Baldomero M. Olivera, Ph.D. Professor Department of Biology University of Utah College of Science Salt Lake City, UT 84112
Larry L. Smarr, Ph.D. Director National Center for Supercomputing Applications University of Illinois Champaign, IL 61820
Executive Secretary Ruth L. Kirschstein, M.D. Deputy Director National Institutes of Health Bethesda, MD 20892
Appendix C – Presenters
David Baltimore, Ph.D. Massachusetts Institute of Technology Director Cambridge, MA 02139
Marvin Cassman, PhD. Director National Institute of General Medical Sciences National Institutes of Health Bethesda, MD 20892-6200
John M. Coffin, PhD. Tufts University School of Medicine Department of Molecular Biology Boston, MA 02111
Ellie Ehrenfeld, Ph.D. Director Division of Research Grants National Institutes of Health Bethesda, MD 20892-776
Anthony Fauci, M.D. Director National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892-2520
Michael Gottesman, M.D. Deputy Director for Intramural Research National Institutes of Health Bethesda, MD 20892-0140
Stephen Katz, M.D., Ph.D. Director National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health Bethesda, MD 20892-2350
John La Montagne,PhD. Director Division of Microbiology and Infectious Diseases National Institutes of Health Bethesda, MD 20852-2350
J. Richard McIntosh, Ph.D. Department of Molecular, Cellular, and Developmental Biology University of Colorado Boulder, CO 80309-0347
William Paul, M.D. Associate Director for AIDS Research National Institutes of Health Bethesda, MD 20892-2340
Anne Thomas Associate Director for Communications National Institutes of Health Bethesda, MD 20892-0188
Appendix D – Related Reports and Articles
Final Report/International Conference on Malaria in Africa Challenges and Opportunities for Cooperation
Sequencing the Genome of the Malaria Parasite The Status Report
Biomedical Research Careers Report on New Investigators
Articles and Others
"African Malaria Studies Draw Attention," Science, January 17,1997
"Malaria Avoidable Catastrophe," Nature, April 10, 1997
January 27, 1997 Agenda/Follow Up to Dakar Meeting and Update of Current Activities:
Update on NIAID Extramural Malaria-Related Research Activities
Minutes from the Strategy and Planning Workshop for Sequencing the Malaria Genome
The Federal Malaria Vaccine Coordinating Committee (FMVCC)
Objectives and Draft Agenda of the Follow Up Meeting of "Dakar," 8–9 July, Scheveningen, The Netherlands
AIDS Activities Facts about the Vaccine Research Center at the National Institutes of Health
Copies of these reports are available upon request. Call (301) 496-0959.