Circulation. 1995;91:487-493
(Circulation. 1995;91:487-493.)
© 1995 American Heart Association, Inc.
American Heart AssociationBugher Foundation Centers for Molecular Biology in the Cardiovascular System
Howard E. Morgan, MD;
Sheryl R. Paul, MSW
From the Sigfried and Janet Weis Center for Research, Geisinger Clinic,
Danville, Pa (H.E.M.), and the Division of Research Administration, American
Heart Association, Inc, Dallas, Tex (S.R.P.).
Correspondence to Howard E. Morgan, MD, Sigfried and Janet Weis Center
for Research, Geisinger Clinic, Danville, PA 17822-2601.
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Abstract
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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 AHABugher Foundation Center program has
produced a cadre of cardiovascular scientists who are applying
molecular biology knowledge to both basic and clinical problems.
Key Words: AHA Medical/Scientific Statements molecular biology cells cardiovascular diseases
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Introduction
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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 AHABugher 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.
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Origins of the Program
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The AHABugher 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 biologycardiovascular" 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 programas 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 AHABugher 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
sciencebeginning 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 positiona 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] bookie,
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
AHABugher 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 AHABugher Foundation
program.
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Award Characteristics
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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 AHABugher 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.
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Program Promotion
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Availability of the AHABugher 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.
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Application Process
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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 AHABugher 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%).
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Selection Process
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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 AHABugher 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.
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Outcomes
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Six AHABugher 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 AHABugher 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
.
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Productivity of the 1986 Centers
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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 AHABugher 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.
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Growth of Molecular Biology in the Program of the AHA
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The emphasis on studies at the molecular and cellular level
that
was a result of the AHABugher 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.
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Summary
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The AHABugher 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.
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Acknowledgments
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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.
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Footnotes
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Reprint requests to Sheryl R. Paul, Director, Division of Research
Administration,
American Heart Association, Inc, 7272 Greenville Ave, Dallas,
TX
75231.