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OCR for page 24
Closing the Bed-Bench Gap
Against this background the Markey Trust began to dedicate some
of its grants to programs offering innovative ways of training
physicians to enable them to engage in basic biomedical and
translational research and to expose Ph.D. scientists to disease-oriented
research. Through the General Organizational Grants program the Trust
requested proposals for two types of grants from selected institutions for
training programs: (1) programs that offered significant clinical exposure
for Ph.D.s during their student years and (2) programs that permitted
M.D.s to engage in research during their years in medical school and
residency.
The Trust's support of organizational grants began with two large
awards to the University of California, San Francisco, and Rockefeller
University that were intended to stimulate organizational change. A law-
suit interrupted dispersal of funds (see Introduction). When the Trust
resumed its grant malting the intention of Me grants had changed from
stimulating organizational change to supporting the training of physi-
cian-scientists. Grants changed from supporting He training of Ph.D. stu-
dents to training both types of students.
The Trust funded a wide variety of training programs for M.D.s.
These programs provided for intense research integrated into medical
school curricula, offered protected time for research during residency,
and developed refresher courses in basic science for M.D.s. In addition)
the Trust funded several programs to provide basic clinical training for
Ph.D.s. For both physician and scientist training programs the Markey
24
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CLOSING THE BED-BENCH GAP
25
trustees wanted to aim for the best candidates at the best institutions, but
institutions differed in how they selected trainees.
General Organizational Grants programs were funded for approxi-
mately five years, although many grant recipients were able to extend the
grant's duration. This section describes the kinds of programs supported
by the Trust to enhance the workforce needed to address bed-bench gaps.
TRAINING PROGRAMS FOR PHYSICIANS
The Markey Trust provided funding to seven institutions that pro-
vided training in basic research to medical students or young physicians.
These programs identified physicians at various stages of medical train-
ing and provided opportunities for them to receive intensive training in
a 1 ~ 1
basic research.
The eight programs provided training and support to 132 physician-
scientists during the 1990s. The total cost of these eight programs was
$14.9 million and the average cost per program per year was about
$317,000. There was a great deal of variation among the programs. One
provided five years of protected time. Other programs provided stipends
for a two- or three-year postdoctoral fellowship. One program offered an
intensive summer program. Programs also varied in terms of the career
stage of participants, duration of funding, and training strategies. The
average cost was about $113, 000 per physician-scientist.
Descriptions of programs that provided training in basic science to
physicians are presented below.
· Children's Hospital Boston/Harvard University ($2,250,000 ~
1993-1998~. The Markey Child Health Research Center program, co-
directed by Philip Pizzo and Stephen Harrison, was aimed at providing
research training for pediatricians. Pizzo believed that pediatricians were
the most endangered group of physician-scientists. A total of 17 young
pediatric investigators received fellowships for one or two years, depend-
ing on the availability of independent funding after the first year. Each
fellow was assigned to a senior faculty mentor to assist in the training
process. The focus of the program was on providing protected tune for
immersion into research.
· The Rockefeller University ($2,500,000 · 1993-1998~. This grant,
developed by Jules Hirsch, provided support for the Clinical Scholars
program in molecular medicine to allow research experiences for physi-
cian faculty. The program established independent laboratories and train-
ing opportunities in research techniques and concepts of modern biology.
Salaries and startup costs for two assistant professors and two medical
fellows were funded.
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26
BRIDGING THE BED-BENCH GAP
· College of Physicians and Surgeons of Columbia University ($2
million · 1993-1998~. The Career Tracks Program in Postgraduate Medi-
cal Education, codirected by Sharon War~llaw and Christopher Schindler,
received a $2 million award. The program was modeled after the success-
ful Johns Hopkins National Research Service Awards program. Its goal
was to provide research training and experience to talented medical school
graduates early in their residency training. Fifteen fellows were selected
for the two-year program after the second or third year of their house staff
residency. During the research-training period residents continued to fol-
low their own patients in the general medicine outpatient clinic in order
to maintain their clinical skills.
· Four Schools' Physician-Scientists Program in Internal Medicine
($3.5 million · 1991-2001~. Alfred Fishman was the coordinator of this
program to develop physician-scientists in the departments of internal
medicine at the University of Pennsylvania, Duke University, Washing-
ton University, and Johns Hopkins University. The four schools program
introduced physicians to basic research in three phases. Phase 1 was a
year of research following the third year of medical education. Phase 2
consisted of clinical research experience during residency. Phase 3 was
two years of postgraduate research experience. Forty-six physicians com-
pleted the program.
· Yale University ($2.1 million · 1993-19981. This grant supported
the physician-scientist training program in which physicians retooled over
a three-year period. Training consisted of a six-month period of labora-
tory courses and 2.5 years of in-depth research supervised by mentors
from both clinical and basic research departments. Developed by I. D.
Jamison, the program provided exposure to basic research for 12 practic-
ing physicians. Each summer the program conducted a two-week inte-
grated lecture and laboratory program in molecular and cellular biology
designed to reacquaint physicians with the basic science necessary to
submit grant applications. This program attracted 20 to 30 participants
annually.
· University of California, San Francisco ($2.5 million · 1992-1999~.
The Molecular Medicine program, directed by Marc Shuman, enabled 31
physicians who were just completing their residency to spend three years
in laboratories of molecular medicine in the university's Program in Bio-
medical Sciences. In addition to research experience fellows also received
extensive coursework in biochemistry, cell biology, and molecular genet-
ics, ensuring that the fellows had a theoretical background comparable to
that of graduate students in biochemistry.
· Brigham and Woman's Hospital ($50,000 · 1994-1995~. Under the
direction of Thomas Stossel this grant supported development of a sum-
mer training program for physicians who were beginning laboratory re-
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CLOSING THE BED-BENCH GAP
27
search training. The program focused on three two-week blocks consist-
ing of biochemistry, molecular biology, and cell biology. Seven students
participated full-time, all day for six weeks through lectures, journal clubs,
and hands-on laboratory experience
To gain a better understanding of how these programs worked and
their impact on biomedical science training, the Markey Evaluation Com-
mittee chose to visit three programs that were representative of this type
of General Organizational Grant: University of California, San Francisco;
College of Physicians and Surgeons of Columbia University; and Chil-
dren's Hospital, Boston/Harvard University. Detailed site visit reports
for these programs are presented in Appendix F. Unfortunately lack of
outcome data on the trainees prevented a deeper evaluation although the
Committee believes the support of such training programs is worthy of
philanthropic attention. Future funders of graduate training programs
should ensure that a comprehensive program evaluation and prospective
monitoring of outcomes is an integral part of the overall design of project.
The approaches taken in many of the training programs, especially those
that provided an extended and in-depth experience in research, are still in
use in many academic centers. The value of flexible and generous dollars
in resource-constrained times was noted by leaders of these programs
during site visits. Summaries of these site visits are in Appendix F.
TRAINING PROGRAMS FOR PH.D. SCIENTISTS
The Markey trustees funded 12 programs that provided clinical expe-
rience to basic scientists. These are listed below. These new experiments
attempted to determine whether Ph.D.s with a better understanding of
clinical problems could better alleviate the ongoing decline of physician-
scientists. One program, at Stanford University, subsequently changed its
focus from clinical to basic research. Of the remaining 11 programs the
programs at Tufts University and Rockefeller University were already
under way when they received Markey grants, having been started in
1986 and the 1970s, respectively. The remaining programs were newly
created with Markey Trust funds.
These 12 programs provided training in patient-oriented pathobiol-
ogy to 430 basic scientists during the 1990s. These programs varied greatly
in form and content, ranging from highly structured four-year programs
to single summer courses. 1h addition, programs offered training to a
wide variety of scientists including undergraduate and graduate students,
postdoctoral fellows, and young faculty. The total cost for the 12 pro-
grams was $39.2 million. The average cost was about $552,000 per pro-
gram per year and about $60,000 per participant.
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28
BRIDGING THE BED-BENCH GAP
A brief description of each of these programs is presented below.
.
Tufts University School of Medicine ($400,000 · 1989-1996~. This
program, built around coursework in pathobiology, has basic scientists at
the graduate school and postdoctoral level analyzing 20 major human
diseases. The students study gross and microscopic pathology, observe
major diagnostic procedures, witness specialized patient care such as re-
nal dialysis and transplantation, and participate in clinical rounds. The
Trust provided funding for 105 students. The program at Tufts is ongoing
and continues to produce scientists versed in disease-oriented research.
Outcome data provided by Arias (2003) show that trainees are working in
research jobs, many in clinical departments.
· Washington University School of Medicine ($4 million · 1992-
19991. This grant, directed by Alan Schwartz and Jeffrey Saffitz, provided
support for the establishment of the Special Emphasis Pathway in Human
Pathobiology. The program provided clinical exposure to 33 predoctoral
and 18 postdoctoral scientists through a series of courses that focused on
a specific disease. In addition to participating in three courses each gradu-
ate student or postdoctoral fellow had dual mentors. The clinical mentor
had the role of integrating students into the culture and practice of the
hospital. This program has been maintained through the combined ef-
forts of the 19 departments in the biological sciences that provide support
amounting to about $200,000 per year.
· Harvard Medical School ($4 million · 1992-1996~. This project,
directed by Franklin Bunn, emphasized the concept of "New Pathways"
and the restructuring of biomedical scientist training. Interaction between
biomedical scientists and student physicians was stressed. Ph.D.s received
a master's degree in medical science. In addition, the program was con-
cerned with career outcomes of Ph.D.s and focused on placing Ph.D.s into
clinical departments. A total of 57 students participated in the program.
· University of California, San Diego ($2.5 million · 1992-1997~.
This program, developed by George Palade, supported the development
of graduate studies in cellular and molecular biology. The program fo-
cused on inter-institutional training at the UCSD School of Medicine, the
Research Institute of Scripps Clinic, the Salk Institute, and the La Jolla
Cancer Center (Burnham Institute) for 89 UCSD graduate students.
· University of Virginia ($800,000 · 1993-1997~. This program, di-
rected by Michael Webber, was designed to prepare scientists to study the
molecular basis of human diseases and to facilitate the interaction be-
tween clinical and basic scientist researchers. The program, which used a
dual-mentor approach for four students per year (a total of 20 students),
consisted of one year of course work followed by two years of blended
clinical and laboratory experience.
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CLOSING THE BED-BENCH GAP
29
· Stanford University ($900,000 · 1993-20011. This grant was in-
tended to enable medical school faculty to develop a new Ph.D. program
in molecular mechanisms of disease under the direction of Michael Lieber,
a Markey scholar. Because of changes by which graduate student tuition
could no longer be reimbursed at universities and He financial difficulties
common to all private medical schools, the program as intended became
financially untenable. Consequently Stanford received permission from
the Markey trustees to use the award to support Ph.D. students in existing
interdepartmental programs whose work focused on the studies of hu-
man disease. These students were under the direction of Joseph Lipsick
and Michael Cleary. Ten students were funded for two years each.
· University of Chicago ($3.2 million · 1993-1998~. The grant, di-
rected by Nancy Schwartz, provided support for a new Ph.D. program in
molecular medicine. The program recruited graduate students to focus on
the biology of human disease using a dual mentor approach. The pro-
gram was part of a new interdisciplinary biological science complex with
clinical and basic science components. Thirteen scientists participated in
the program that bridged the gap between basic science research and its
relevance to human biology and disease processes.
· Johns Hopkins University ($3.2 million · 1994-2000~. This grant,
directed by Thomas Pollard and Peter Agre, developed a cross-depart-
mental program in cellular and molecular medicine. Students took course
work in biochemistry, cellular and molecular biology, neuroscience, hu-
man genetics, and physiological and pathological basis for human dis-
ease. Trainees had access to research opportunities in basic science and
access to clinical faculty with joint appointments. There were over 450
applicants to the program and 43 graduate students participated. The
Johns Hopkins program was able to redefine its orientation so that it
received a training grant from the National Institute of General Medical
Sciences of the NIH.
· Carnegie Mellon University ($1.4 million · 1994-1999~. This grant
supplemented National Science Foundation-funded support for the Sci-
ence and Technology Center. The program provides training in advanced
technology and equipment for nine young faculty members in basic sci-
ences, five postdoctoral scientists, four graduate students, one computer
engineer, and two technicians. This program anticipated the interdepen-
dence of modern medicine and technology. The primary areas of empha-
sis included structural and developmental biology, computational biology
and chemistry, microscopy and imaging technology, and in viva imaging.
Lansing Taylor was the program director.
· University of Cincinnati ($50,000 · 1995-19961. The program on
pathobiology and molecular medicine was developed to encourage and
foster the performance of translational biomedical research by graduate
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30
BRIDGING THE BED-BENCH GAP
students and was modeled after Irwin Arias's program at Tufts. Gregory
Retzinger, a Markey scholar, used funding from the Markey Trust to
develop the course in pathobiology of disease taught by the departments
of pathology and laboratory medicine (taken by eight graduate students).
Intramural funding has allowed this approach to translational research to
continue.
· University of California, San Francisco ($13,750,000 · 1988-1995~.
Under the leadership of Michael Bishop, the Markey award, combined
with funds from other sources, was used to fund an extensive reorganiza-
tion of the graduate programs in biomedical sciences. Under this proposal
the programs in biochemistry and molecular biology, cell biology, immu-
nology, neurobiology, and genetics were merged into a new program in
biological sciences. Unlike the other General Organizational Grants this
award was used primarily to restructure the programs in biomedical re-
search and included a component to provide medical experience for
graduate and postdoctoral students. Most of the funds were used for
equipment, supplies, and construction.
· Rockefeller University ($5 million · 1989-1993~. Markey Trust
funds supplemented the University Fellows program, originally devel-
oped in the 1970s. University fellows were mature scientists with at least
three years of postdoctoral experience and established research agendas.
Thorsten Wiesel directed the program. Markey Trust funds supported 13
university fellows as assistant professors and included salary support,
equipment, supplies, and renovation. Four of the university scholars were
also Markey scholars and seven subsequently became Howard Hughes
Medical Institute investigators.
The directors of six of these programs participated in the National
Research Council-sponsored Workshop on Training Programs in Patient-
Oriented Pathobiology for Basic Scientists in October 1999. These direc-
tors presented detailed information on the overall description and history
of their program, the program's efforts to bridge the bed-bench gap,
characteristics of applicants and students in the program, and a summary
of program finances. Summaries of the presentations of each of the six
programs are presented in Appendix E.
TRAINING PROGRAMS FOR BOTH PH.D. SCIENTISTS
AND PHYSICIANS
The Markey Trust funded three programs that provided training in
translational research for both physicians and scientists. A wide variety of
predoctoral, postdoctoral, and young faculty received funding from these
hybrid programs. A total of $6.4 million was expended to cover the sti-
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CLOSING THE BED-BENCH GAP
31
Fends of 55 scholars. The cost was $320,000 per program per year, or
about $116,000 per fellow. A brief description of these programs follows.
· University of Utah ($2 million · 1994-1999~. This grant supported
an expansion of the program in human molecular biology and genetics,
an interdepartmental effort to strengthen the interface between clinical
and basic investigators. The goal was to provide protected time, a five-
year research experience without interruption for six M.D. and Ph.D.
young faculty. While the majority of funding was restricted to faculty
salaries, a significant proportion of funding (about 30 percent) was for
equipment. Stephen Prescott and Raymond White were the co-principal
investigators.
· Cornell University Medical College and Memorial Sloan-Ketter-
ing ($2.4 million · 1994-2000~. This grant supported multidisciplinary
training in both institutions. Trainees included 10 Ph.D. candidates, 10
M.D. postdoctoral fellows, and 6 M.D./Ph.D. physician-scientists. The
goals of the program were (1) to train a new generation of scientists to be
competent to perform modern molecular and cell research and possess
the knowledge to identify and address questions related to human dis-
ease and (2) to create an environment that enabled laboratory scientists
with expertise in basic biology to interact regularly with investigators
who approach research from a disease-oriented perspective. This pro-
gram was delayed due to external factors; the initial cohort of students
arrived in 1995. The majority of funding was directed toward salaries.
Marvin Gershengorn and Richard Rifkind were the principal investiga-
tors and, because of the flexibility of funding, were able to extend the
program several years.
· Emory University ($2 million · 1994-2000~. This program estab-
lished a new department in neurosciences. While it was more research
oriented than the other General Organizational Grants, the focus of fund-
ing was on the development of the Center for Neurological Sciences. The
grant provided stipend support for M.D. /Ph.D., M.D., and Ph.D. postdoc-
toral fellows, junior faculty, and visiting scientists in neurodegenerative
diseases, movement disorders, psychiatric syndromes, and epilepsy and
stroke through shared courses, seminars, and grand rounds. Eighteen
postdoctoral and two predoctoral fellows, three junior faculty, and one
visiting faculty was supported by Markey Trust funds. The co-principal
investigators were Donald Humphrey and Jeffrey Houpt.
Representative terms from entire chapter:
provided training
