Background The American Heart Association (AHA) and the Henrietta B. and Frederick H. Bugher Foundation in 1985 entered into a partnership to establish a group of Centers for Molecular Biology in the Cardiovascular System. The goal was to recruit and train young scientists with medical training to apply molecular and cellular biology knowledge and techniques to cardiovascular problems.
Methods and Results Six Centers have been awarded (three in 1986 and three in 1991), and a total of 110 trainees have been involved as of June 30, 1994. Of these trainees, 77 were recruited and trained by the 1986 Centers. As of June 1994, 88% of these trainees remained in academic medicine and 54% progressed to higher academic ranks; 79% published papers in science and 66% in molecular biology; and 36% obtained extramural funding for their work. On this basis, the 1986 trainees appear to be well on their way to becoming successful academic cardiologists.
Conclusions The AHA–Bugher Foundation Center program has produced a cadre of cardiovascular scientists who are applying molecular biology knowledge to both basic and clinical problems.
In 1985, the American Heart Association (AHA) entered into partnership with the Henrietta B. and Frederick H. Bugher Foundation to establish an integrated, institution-based research program to train promising individuals with cardiovascular medicine backgrounds in molecular biology research techniques. The program, entitled the AHA–Bugher Foundation Centers for Molecular Biology in the Cardiovascular System, was designed to achieve two specific objectives: (1) to stimulate and enhance application of the science of molecular biology to study of components of the cardiovascular system and (2) to recruit and train young scientists with medical training to enter research careers in molecular biology of the cardiovascular system. To clarify the program’s scientific focus, molecular biology was defined as “studies of cell biology that address the molecular basis of the structure and functions of genes, proteins, and cells.” As envisioned, the Center concept not only promoted the development of a focus of research work in the application of molecular biology to cardiovascular research but also encouraged the establishment of model training programs by which to develop a cadre of scientists with expertise in this area.
Origins of the Program
The AHA–Bugher Foundation program arose from the origins and goals of both organizations. In a letter to one of us (H.E.M.), D. Nelson Adams, Esquire, Senior Trustee, the Bugher Foundation, described the origins of the Foundation.
The Foundation was established many years ago during Fred Bugher’s lifetime with a token grant. The purpose, of course, was to create a vehicle that could be qualified as “charitable” for IRS purposes to which Fred, who had no family of his own, could leave the bulk of his not inconsiderable estate. Fred instructed me as his lawyer to provide that the purpose of the trust should be to support research in cardiovascular disease. Both his parents had suffered from heart ailments. Fred also had a fond yearning for the District of Columbia and, pursuant to his wishes, the trust initially was limited to research within the District. It was not easy to move Fred, but some years later I managed to persuade him that this geographical limitation was unreasonable and he agreed to an amendment which in a stroke expanded the boundaries of the District to the world at large.
In Fred’s lifetime the trustees consisted of Fred, Douglas Smith, his longtime friend and banker in Washington, and myself. On Fred’s death, we elected Bob Robinson, then president of the Episcopal Church Pension Fund and an old friend of mine, to take Fred’s place. Inasmuch as we were lacking in any medical knowledge, we recognized at the outset that we needed professional guidance. To his credit, Douglas Smith suggested that we talk to Dudley Hafner of AHA. A luncheon was arranged at the Metropolitan Club in Washington at which Dudley assured us that we had come to the right place. This in turn led promptly to a luncheon meeting at the Wall Street Club in [New York City] with the current leaders of AHA. At this meeting, Howard, you in your quiet but persuasive way told us that while much research had been done in recent years in the field of molecular biology, practically nothing had been done to bring molecular biology into the orbit of cardiovascular disease. Furthermore, you told us that in medicine generally there was a crying need for scientists who would devote their careers to medical research. Putting the two disparate factors together, you said that with adequate funding there was a compelling opportunity to create centers where molecular biology of the heart could be featured in conjunction with the training of young scientists who would be encouraged to devote their lives to medical research.
We agreed to provide the funding and you took it from there. I can only say that I have marveled at the efficiency of the AHA and the dedication of the many busy doctors who volunteer their services. The process by which six laboratories around the country have been selected to establish the Centers is a model of intelligent planning, thoroughness, and fairness.
Dudley H. Hafner, Executive Vice President of the AHA, described the origins of the program as follows.
[I received a] phone call from Doug Smith of Washington, DC, now deceased, in early August 1984 stating that he was one of three trustees of an estate that would distribute proceeds for cardiovascular disease research. He explained that he and the other two needed help in interacting with the research community. We set a date for me to meet with Mr Smith at his club in Washington at the end of August.
As the result of this meeting with Mr Smith, I believed that a program that would identify specifically with the Bugher Foundation and break new research ground would be exciting to the trustees. Funding of ongoing existing research programs would not likely be attractive.
On returning from Washington, I described the opportunity to Mary Jane Jesse. I understand that Mary Jane talked to Howard Morgan and Saul Winegrad individually and that both felt the greatest opportunities were in the “molecular biology–cardiovascular” arena.
Saul Winegrad, as chair of [the] Research [Committee], accepted the situation as one of offering help to the Foundation trustees to do something that was uniquely their own. It was Foundation money, Foundation mission, and trustees wanting help. Saul and Mary Jane formed a “team” of Morgan, Jesse, Bernadine Healy, and Winegrad to develop suggestions. The idea of molecular biology quickly moved to the top of that list.
In September, I arranged with Doug Smith to visit the three trustees, ie, Nelson Adams, Doug Smith, and Robert Robinson in New York City to explain peer review and project management and to also discuss making a major long-term commitment to a specific area that could become identified with the Bugher Foundation (like the Sarnoff). They wanted to know what AHA’s role would be, and I said to help the trustees any way we could to fund high-quality research. Throughout, one might say they never gave AHA money, but instead asked AHA to run a new research program they would pay for. It was under this banner that the Research Committee agreed to accept the responsibility.
The meeting between the trustees and the AHA team of Jesse, Winegrad, Morgan, and Healy took place December 7, 1984, in New York City. Molecular biology along with other possibilities were presented. The trustees wanted the molecular biology program, wanted to fund it, and wanted AHA to manage it. The trustees’ official decision was made in late March 1985.
The Research Committee agreed to authorize the creation of the appropriate structure to handle the center program—as long as it did not take money away from AHA’s existing award programs.
Mary Jane Jesse, MD, past president of the AHA and later senior vice president for scientific affairs at the National Center, managed the AHA–Bugher Foundation program. She described the events as follows in a letter to H.E.M.
At the time that I wrote the talk that I gave as the president’s address in November of 1982, the concept of a center for molecular biology was rattling around in my head. You may recall that I had talked about the exciting developments that were occurring in basic science—beginning with the very late recognition of what Barbara McClintock had contributed. At that point, I didn’t know that I was going to end up at AHA in a staff position—a new position at that time to address scientific affairs.
I believe that I even discussed the potential for AHA funding such a center or centers with Dudley not long after I arrived in Dallas.
Meanwhile, Dudley was working hard to find sponsors for AHA research, and the relationship with the Bugher Foundation developed from his pursuing it with vigor.
When it became apparent that the Bugher people were interested, . . . I suggested to Dudley that you and Saul Winegrad along with Bernadine Healy would make a good group to present the idea of a molecular biology center or centers to the trustees of the Foundation. Meanwhile, I had talked with Saul about the use of a chapter out of NHLBI’s [National Heart, Lung, and Blood Institute] book—ie, developing a special request for applications and having the applications reviewed by a special study group headed by you. As you may remember, the world wasn’t exactly overrun with molecular biologists at the time, and I was anxious that we have a study group that was well qualified. Saul had no objections to this plan, in his role as the chairman of the research committee.
So far as other alternatives for the Bugher monies [are concerned], there really weren’t any . . . nor, I confess, did I look for any.
Developing what amounted to an RFA for applications for the Centers was simple enough. I just lifted what I had done at NHLBI and we were off and running.
None of this would have happened if Dudley hadn’t been the prime mover in developing the funds. He was excited about the AHA being a leader in the molecular biology business.
The authors of this paper have been actively involved with the AHA–Bugher Foundation program since 1984. H.E.M. served as chairman of the peer review group for rounds one and two of the application and award process. Peer review was not managed directly by the Research Committee because many members of the Committee were affiliated with institutions that were applicants. Contacts with the Bugher Foundation trustees also have been maintained. S.R.P. is Director of Research Administration for the AHA and has been responsible for both rounds of peer review and day-to-day management of the AHA–Bugher Foundation program.
The Bugher Foundation’s continuing interest in and support of this innovative AHA research program led to two separate rounds of competitive applications, and two sets of AHA–Bugher Center awards were activated over the past 10 years (1986, 1991). Each institutional award provided 5 years of financial support in the following total amounts: round 1 (1986 Centers): $1 125 000 per award and round 2 (1991 Centers): $1 250 000 per award. Each award was given as one-time-only support. Center awardees were and continue to be excluded from competition for a second award at any subsequent time.
The bulk of Center funding (75% to 80%) was expected to be allocated for salaries of trainee/fellows. Fellowship slots were targeted to MDs (or MD/PhDs without relevant postdoctoral research training) who had, in whole or in part, completed a clinical residency program and who could devote at least 80% of their time to participation in the program. US citizens and permanent residents were eligible to receive Center funding; however, resident aliens who met all other trainee/fellow eligibility requirements were permitted, at the discretion of the Center director, to fully participate in the program without benefit of financial support. The remaining Center funds (20% to 25%) could be spent on research supplies, trainee/fellow seminars or travel, and other salaries. Up to 8% of the total award amount could be used to defray indirect costs. Support for project grants, equipment, capital purchases/improvements, patient care, tuition, and miscellaneous other trainee/fellow perquisites was not allowed.
Availability of the AHA–Bugher Foundation Center program was widely promoted to 126 US medical schools and other nonprofit academic institutions well in advance of the application deadline. Informational posters were distributed to institution-based faculty, and advertisements were placed in AHA scientific journals. Any institution that could demonstrate the existence of or a thoughtful plan to acquire (1) a program in molecular, cellular, and/or genetic biology, (2) a program for fundamental studies of cardiovascular function, and (3) access to clinical investigators with expertise in the analysis of cardiovascular function was urged to explore this innovative avenue for research training support.
The AHA adopted a two-phase application process. Phase 1 requested formulation of a one-page letter of intent outlining proposed areas of research and, in the event of planned collaborative arrangements, identification of other participating institutions. This process permitted early projection of the potential volume and identity of program applicants and, when multiple letters were submitted from a single institution, clearly identified the need for intrainstitutional coordination. A set of application forms was sent to all institutions that submitted letters of intent. Phase 2 required the completion and submission of a formal proposal in accordance with guidance provided by the AHA as to content, structure, and eligibility criteria. Only one application could be submitted by or accepted from a single institution.
The written proposal required six elements to be fully described: (1) a molecular biology program, (2) a program of basic research in the cardiovascular system, (3) expertise in clinical cardiovascular investigation, (4) qualifications of the nominated director, (5) a plan for integrating molecular biology with existing basic research programs, and (6) a fellow training plan.
The number of letters of intent submitted and formal proposals received in rounds 1 and 2 of competition for AHA–Bugher Foundation Center funding were as follows: round 1, 62 letters of intent submitted and 24 applications received (39%); round 2, 52 letters of intent submitted and 18 applications received (35%).
Responsibility for assessing scientific merit and establishing a rank-ordered list of submitted applications was assigned to a volunteer peer review group organized for that specific purpose. A minimum of 12 senior investigators of international stature was selected primarily on the basis of their science expertise and absence of institutional conflicts of interest. Secondary considerations included knowledge of AHA research policies, inclusiveness, and ability to fulfill all required duties. The committee, composed of relatively equal numbers of basic research and clinical training experts, conducted its work in compliance with established AHA research policies governing professional/personal conflict of interest avoidance, voting, scoring, and subsequent communications with applicants and other interested parties.
Peer review was conducted in two sessions: Session 1 consisted of a face-to-face meeting of the peer review group for the purpose of evaluating submitted proposals in accordance with publicized assessment criteria and identifying, on the basis of scientific merit, a number of finalists for funding consideration. Session 2 was organized on a reverse site visit model. Representatives from the finalist institutions were invited to meet and interact with the final selection committee and Bugher Foundation trustees. At the conclusion of this meeting, second-round scores were rank ordered and awards were recommended for the most meritorious proposals.
In both peer review sessions, Center applications were evaluated on the following items: (1) Center faculty’s capabilities (present/expected) in molecular biology and basic cardiovascular research, their capacity for direct interaction with clinicians in cardiovascular diagnosis and therapy, commitment, and time; (2) Center director’s qualifications, experience, and commitment; (3) integration plan for merging research capacities into a Center with a coordinated study program; (4) selection process and training program for fellows, including anticipated formal course work, qualifications of designated mentors, preceptors for each section of the training program, and resources available to and expected accomplishments of trainee/fellows; (5) resources, including institutional commitment to the program, adequacy of existing resources and plans for use of Center funds to augment training resources, and ability to administer a Center program; (6) scientific/administrative structure, including procedures for monitoring/evaluating proposed research, quality control, and scientific review mechanisms; and (7) budget. The number of applications reviewed, finalists selected, and awards approved for activation in rounds 1 and 2 of competition for AHA–Bugher Foundation Center funding were as follows: round 1, 24 applications received, 5 finalists selected (21%), and 3 awards made; round 2, 18 applications reviewed, 7 finalists selected (39%), and 3 awards made.
Six AHA–Bugher Foundation Centers for Molecular Biology in the Cardiovascular System have been awarded over $8 million through two discrete competitions, as follows: (1) 1986 Center Awards ($4 275 000): (a) Baylor College of Medicine (Houston, Tex), (b) Children’s Hospital (Boston, Mass), and (c) University of Texas Southwestern Medical Center (UTSW) (Dallas, Tex) and (2) 1991 Center Awards ($3 750 000): (a) Brigham and Women’s Hospital (Boston, Mass), (b) Stanford University (Stanford, Calif), and (c) University of California, San Diego (La Jolla, Calif).
The Centers that were established in 1986 were offered the opportunity to apply for two additional years of support at a maximum level of $200 000/y at the time of the round 2 decision-making process. Extension requests and funds were managed separately from the competition for new awards.
As of June 30, 1994, the six AHA–Bugher Foundation Centers have trained 110 MD fellows to conduct research related to the molecular biology of the cardiovascular system. Of that number, 72% have received direct salary support from Center awards. The remaining 28% have participated in the program in an honorary capacity, fulfilling all requirements and possessing the designation of trainee/fellow without benefit of Center funding. An enrollment summary is shown in Table 1⇓.
Productivity of the 1986 Centers
At the time of their appointment, the trainees were either cardiology or postdoctoral fellows or instructors (Tables 2 through 4⇓⇓⇓). In 1994, 53% of trainees (41 persons) had achieved the rank of assistant professor, and 1 trainee was a professor (Table 5⇓). Thirty-five percent remained as fellows or instructors, 8% were in practice, and 3% could not be contacted. Forty-seven percent of trainees were still located at their training sites, and 40% had moved to other research positions within the United States.
Sixty-one of the 77 trainees (79%) published a total of 817 scientific papers in the period between 1986 and 1993 (Table 6⇓). The range in number of publications was from 1 to 200 per trainee. The mean number of publications per trainee was 13.4, but the mean was distorted by two trainees with more than 100 publications each. As a result, the median numbers of publications are reported in Table 6⇓. A median number of 5 publications, with 3 as first author, was published by each trainee. Approximately the same percentage of trainees published at each site, but the median number of scientific publications per trainee was 2.4- to 3.6-fold greater at Children’s Hospital, Boston than at Baylor or UTSW, respectively.
Of the 817 publications, 316 papers were judged by the AHA scientific staff to contain subject matter in the molecular biology area. The range of number of molecular biology publications varied from 1 to 39. The mean number of publications was 6.2 per trainee, and the median number was 3 papers per trainee. The trainee was first author on 2 of these papers. Approximately 66% of trainees published molecular biology papers, and the median number of molecular biology papers published per trainee was approximately the same at each site.
Extramural funding awards to AHA–Bugher Fellows through 1994-1995 totalled $10 903 088 and were made up of 58 awards to 28 trainee/investigators (Table 7⇓). Approximately 70% of the funds were awarded by the National Institutes of Health and 30% by the AHA. The percentage of fellows who received awards varied from 14% at Baylor to 38% at UTSW to 62% at Children’s Hospital. Of the total funds, 81.8% was awarded to trainees of the Children’s Hospital program.
In our opinion, the 1986 training sites produced trainees who are well on their way to becoming successful academic cardiologists, because 88% remained in academic medicine and, as of 1994, 54% progressed to higher academic ranks, 66% published papers in molecular biology, 79% published papers in science, and 36% of the total group obtained extramural funding for their work. A longer-term follow-up of the group will be necessary to assess the final outcome.
Sufficient time has not elapsed to evaluate the 1991 Center trainees in terms of career progression and publication record. Thus far, 10 of the 33 trainees have attracted $1 432 501 of extramural funds through fiscal year 1994-1995. Seventy-one percent of the monies was awarded to trainees at University of California, San Diego. Sixty-nine percent of the monies awarded to all three sites was for stipends.
Growth of Molecular Biology in the Program of the AHA
The emphasis on studies at the molecular and cellular level that was a result of the AHA–Bugher Centers, together with rapid growth of knowledge and numbers of molecular/cell biologists in the scientific community and with funding of molecular studies by the National Institutes of Health, the AHA, and other volunteer health agencies, has increased the representation of molecular studies in the research awards of the AHA and in the programs of the annual Scientific Sessions. The total number of applications reviewed by the AHA increased 37% from 1983 to 1993, while the number of applications in molecular, cellular, and structural biology has increased 23-fold (Table 8⇓). In 1983, molecular studies accounted for 2.3% of applications but 7.7% of awards, because 95% were funded. By 1992, the number of awards for molecular studies had increased sixfold, but the percentage of applications that were funded had fallen to 25%, a success rate that was still somewhat higher than the total applicant pool (21%).
In regard to the AHA Scientific Sessions, the number of abstracts submitted and accepted in the areas of molecular and cell biology increased approximately sevenfold from 1986 to 1993 (Table 9⇓). Over this same period, the total number of abstracts submitted increased 1.85-fold. The percentage of molecular/cellular abstracts accepted has been higher throughout this period and reached a 22% more favorable acceptance rate in 1993. These results indicate that the community of cardiovascular scientists has adopted the approaches and methodology of cell and molecular biology and successfully applied these techniques to cardiovascular research problems.
The AHA–Bugher Foundation Centers for Molecular Biology in the Cardiovascular System represent an important achievement of the AHA and the Bugher Foundation. The foresight and energy of a group of AHA volunteers and staff conceived of the program and gained the continuing support of the Bugher Foundation trustees. The program was planned and implemented expeditiously. The result is a cadre of cardiovascular scientists who are applying molecular biology knowledge to both basic and clinical problems. Few other programs of the AHA have as great a potential to reduce premature death and disability due to heart disease and stroke, the mission of the AHA.
The authors wish to thank the following members of the AHA staff for their help in assembling the data and constructing the tables: Betty Mooz, PhD, Science Review Coordinator, Scientific Affairs; Patricia Hinton, Program and Evaluation Consultant, Research Administration; Stephanie Williams, Awards Specialist, Research Administration; Sandy Thomas, Research Administration Assistant; Sara Owens, Scientific Sessions Program Assistant, Scientific and Corporate Meetings; and Kay Johnson, Manager, Scientific Sessions Program, Scientific and Corporate Meetings. We wish to thank Donna Morgan, Administrative Aide for Research, Geisinger Clinic, for her help in editing the manuscript.
Reprint requests to Sheryl R. Paul, Director, Division of Research Administration, American Heart Association, Inc, 7272 Greenville Ave, Dallas, TX 75231.
- Copyright © 1995 by American Heart Association