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Summary of Site Visits to
Markey-Funded Programs
That Provided Training in Basic
Research to Physicians
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
MOLECULAR MEDICINE PROGRAM
The University of California, San Francisco, Molecular Medicine pro-
gram was developed to address the problem of declining numbers of
M.D. investigators just as biomedical science stood on the threshold of a
new era. Currently most physician-scientists start their training in re-
search only after four years of medical school and a minimum of four
years of clinical trairung. Their initial research experience occurs when
they are in their late twenties or early thirties. There is typically no re-
quirement for formal coursework in the biological sciences or for contact
with the preclinical faculty. These factors make it nearly impossible for
promising physician-scientists to assimilate a new language and a new
way of Winking that integrates the biomedical sciences. Training has gen-
erally been limited to clinical departments and is critically inbred. Most
physician-scientist faculty train their students in exactly the same ways
they were trained. This system favors short-term over open-ended inves-
tigations and its isolation deters the assimilation of new ideas and tech-
nologies.
The Molecular Medicine program (MMP) overcomes these problems
in training physician-scientists by integrating their training with the Pro-
gram in Biomedical Sciences (FIBS), an umbrella organization of biologi-
cal science disciplines. Fellowship positions are available at different
stages of clinical training: in conjunction with residency training or post-
109
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0
APPENDIX F
clinical fellowshi ?. At the time of acceptance into the program MMP
fellows are guaranteed access to three years of training positions in labo-
ratories of molecular medicine or other appropriate faculty either in the
Program in Biomedical Sciences or the Biomedical Sciences program. A1-
though funding for three years of research is guaranteed, the fellows can
accept alternative sources of funding, which may provide greater finan-
cial support and national prestige. Participating faculty are members of
interdisciplinary programs, including Biochemistry and Molecular Biol-
ogy, Immunology, Microbiology, Cell Biology, Developmental Biology,
Genetics, and Neuroscience.
The MMP is designed primarily for individuals who have completed
medical school and are entering internship. Candidates are expected to
have a strong science background and a demonstrated commitment to
laboratory investigation. Candidates are screened by both clinical and
research faculty, and the candidates must meet the academic rigor ex-
pected of the basic scientists in the Program in Biomedical Sciences. Fel-
lows take rigorous coursework in biochemistry, cell biology, and molec-
ular genetics. This assures that fellows have a theoretical background
comparable to those with graduate degrees in biochemistry. To date, 35
individuals have participated in the MMP, which began accepting fellows
in 1992.
MEETING WITH DAN GANEM, ORIGINAL PROGRAM
DIRECTOR
The site visit team met with Don Ganem, the originator of the MMP,
who described its history and evolution. The program was designed to
attract M.D. candidates who were finishing a UCSF residency or the clini-
cal portion of a fellowship. Candidates were not expected to have an
extensive research background, as the idea was to identify and develop
talented trainees for careers as physician-scientists who might not other-
wise have had this opportunity.
Originally the mission was to develop a new program in the Markey
Program in Biological Sciences (P1BS), called the Program in Biomedical
Sciences (BMS) that would focus on disease-related research. However,
there were very few physician-scientist faculty in this program and fur-
thermore, their research was not always valued by the more traditional
Ph.D. scientists. The clinical departments did not relate well to the PIES
and had not been encouraged to cooperate. The clinical faculty either did
not have the pedagogical skills or did not appreciate the structure of
graduate education. This lack of cooperation was perhaps due to the fact
that the clinical faculty was not involved in the initial planning of the
program to develop the BMS.
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APPENDIX F
111
Early in the BMS's development the fellows were required to take
PIBS basic science courses. These courses were selective and very labor
intensive for both faculty and students, which resulted in very high qual-
ity, but put clinical faculty and students at a disadvantage. The PIBS
faculty viewed disease-related science as an enrichment activity and did
not initially appreciate the depth of curricula necessary for training clini-
cally oriented scientists.
Because of the faculty tensions, the lack of depth in disease-related
research, and the disadvantage of clinical students in the PIBS and EMS,
Dr. Ganem proposed that Markey funding be used to develop a parallel
Molecular Medicine program (MMP) that allowed off-campus instruction
and modified entry criteria for clinical faculty. This new development
reduced resistance from clinical faculty. Existing course work in cell biol-
ogy and genetics was used, but the new program also introduced course
work in tissues and organs.
By 1996 when Marc Shuman became director of the program, it be-
came apparent that changes were required in the admissions procedure.
Previously fellows were recruited primarily from UCSF. In an attempt to
attract more and better-qualified candidates the program administrators
decided to focus on a national recruiting effort of M.D./Ph.D. fellows.
Before 1996, 21 fellows were admitted and only one was an M.D./Ph.D.
Between 1996 and the current time 14 fellows were admitted all with
M.D./Ph.D. degrees. Currently about two-thirds of the fellows are sup-
ported by research grants. About three-fourths of the fellows in the initial
cohorts work in academic medical centers. Part of the focus on recruiting
M.D./Ph.D. fellows was a consequence of the realization that the struc-
ture of teaching hospitals has changed. With the emergence of managed
care the focus is on getting patients out of the hospital as quickly as
possible. Attending physicians cannot spend their time on teaching the
science of the patient's illness, efficiency in medicine, or outcomes re-
search.
Recruiting for fellows who would enter into the program in 2001 was
begun. The applicant pool was about 65 candidates, of whom two-thirds
were M.D./Ph.D.s. Four candidates had been accepted for the 2001 class.
MEETING WITH PROGRAM FACULTY AND MENTORS
Faculty attending this portion of the site visit were Art Weiss, Shaun
Coughlin, Mark Goldsmith, Don Ganem, and Marc Shuman. The faculty
emphasized the changing nature of academic medical centers. Because of
managed care, hospitals are required to release patients sooner than be-
fore. Attending physicians do not have the opportunity to observe and
study disease processes. Outcomes research has practically vanished from
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112
APPENDIX F
the teaching hospital. Those residents on the primary care track receive a
good amount of sunnort while medical track residents often seem to
flounder.
--r r ~~ ~'
The faculty stressed the importance of the organizational culture of
the institution. For example, the faculty believes that the PIES would not
succeed at institutions like Harvard because of their exclusively depart-
mental focus.
Mentorship, a clear pathway for the physician-scientist, and an un-
derstanding of the value of disease-related research are the most impor-
tant contributions of the MMP. The faculty also stated that disease-ori-
ented research is the domain of the M.D./Ph.D., while patient-oriented
research may be more effectively done by an M.D. with some scientific
. .
trammg.
MEETING WITH MMP FELLOWS
Fellows attending this portion of the visit were Dan Lerner, Joshua
Reddy, Robin Shaw, Michelle Herrington, Andrai Goga, Chris Haqq, Al
Fisher, Tony Gerber, and Mary Beth Humphrey. These fellows over-
whelmingly stated that the main attraction of UCSF and the MMP was the
guaranteed funding for research. Not only was funding secure but the
stipend was about 25 percent greater than NIH stipends. The fellows also
take advantage of short-tracking (exchanging one year of residency for
one year of research) their training. The fellows found that Markey has
enabled them to collect pilot data, which helped them obtain initial grants.
They reported that they felt supported by He clinical faculty while doing
their research and that the MMP status gave them access to labs that they
might otherwise not have had.
The fellows also reported a few disadvantages of the MMP. There is a
lack of protected time while an intern or resident, which hinders them
from starting their research; sometimes the lab director's interest and the
fellow's interest are not compatible; and there is no formalized mentor-
ship. Marc Shuman does most of the mentoring, and while he does a very
good job (the fellows spoke very highly of him), the program is getting
too large for him to effectively continue in this capacity.
FINANCIAL DATA
Because many fellows obtain funding through multiple sources, Mar-
key funds have been shepherded. Consequently Markey funding will end
in three years; UCSF administration is committed to continuing the MMP.
Fellows for the 2001 academic year are actively being recruited, and they
will require funding beyond that provided by the Markey award.
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APPENDIX F
113
SUMMARY
The Molecular Medicine program is a highly organized training pro-
gram that takes advantage of the resources available at UCSF. The leaders
of the FIBS recognized that they had a medical mission, and the MMP
emerged as a way to fulfill that mission. The organizational culture at
UCSF that led to the development of the PIBS was an essential element in
the development of the MMP.
The site visit team came to three major conclusions about the pro-
gram.
1. To replicate this program, a critical mass of physician-scientists
who are externally motivated (not just interested in their particular field)
is needed. There would have to be a minimum of six faculty and their labs
along with support from the chair or dean.
2. The residents need stronger mentorship to keep them in touch
with science. Marc Shuman, who currently serves as program director
and mentor to all the fellows, will soon become overwhelmed. The fel-
lows are concerned about mentoring, especially while they are residents.
3. The MMP fellows know in general what they want to do when
they arrive at UCSF. They know the subspecialty and the direction of
research, even to the point of knowing the lab they want to work in. These
are highly motivated students who will probably do well wherever they
decide to train.
COLLEGE OF PHYSICIANS AND SURGEONS
OF COLUMBIA UNIVERSITY
CAREER TRACKS PROGRAM IN
POSTGRADUATE MEDICAL EDUCATION
Myron Weisfeldt, the program director, described the purpose and
mission of the Career Tracks program at the College of Physicians and
Surgeons at Columbia University (Columbia-P&S). Before coming to Co-
lumbia P&S Dr. Weisfeldt directed the Johns Hopkins National Research
Service Awards training program. It was very successful in producing a
number of academic physicians in national and university leadership po-
sitions. He decided to implement a similar model of training physicians in
research at Columbia-P&S. With the support from both the medical school
administration and basic science faculty the Career Tracks program was
developed. The goals of the program are to facilitate the clinical and
research training and career development of talented medical school
graduates who enter residency-training programs at Columbia-P&S with
an M.D. /Ph.D. degree or other evidence of a strong research background.
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114
APPENDIX F
The typical training pattern for physician-scientists is believed to be
too clinically intense (up to six years following the M.D.) before any train-
ing in research is introduced. In the Career Tracks program research train-
~ng begins following the second or third year of house staff training. The
program provides two years of training in biomedical research, with sub-
specialty training following the Career Tracks program. Because Dr. Weis-
feldt felt strongly that exposure to basic research must take place early in
the training period, Markey funds were not available to persons with
more advanced clinical training, or to those who wanted to return to the
research lab after subspecialty training.
There are four tracks in the Career Tracks program at Columbia-P&S:
(1-) basic research, which is the Markey-funded track; (2) clinical research;
(3) traditional internal medicine; and (4) general medicine. These tracks
are offered following the first two years of residency. At the conclusion of
their clinical training period residents interested in either research track
will have the opportunity to identify a research mentor and laboratory in
which to conduct research. Research in the chosen basic or clinical labora-
tories begins after the second or third years of residency, and the period
of support is usually two to three years. Thus, residents selected for the
research tracks after two years of residency training will be eligible for
certification in internal medicine after a combined total of five years of
training. If the research is performed in connection with a subspecialty
training program, the resident will become eligible for combined certifi-
cation in internal medicine and the subspecialty after six or seven years,
depending on the subspecialty area. During the research-tra~ning period
residents will continue to follow their own patients in the general medi-
cine outpatient clinic to maintain their clinical skills. Each year the Co-
lumbia-P&S house staff comprises about 40 persons. From this cohort
approximately eight persons indicate some interest in the basic research
career track and three or four are admitted to the program.
A key component of the program is career planning and guidance.
House staff who are interested in the basic science track notify program
directors by the end of their first or begnuung of their second year. Indi-
vidual meetings with the program directors are arranged to discuss spe-
cific plans, including career plans, laboratory possibilities, and timetables.
In the months that follow the interested house staff meet with laboratory
heads to make a final decision as to lab choice. House staff then submit a
letter of intent, which includes overall career plans, a CV, general re-
search interests, and their chosen laboratory. A committee consisting of
program directors and Dr. Weisfeldt make program acceptance decisions.
Progress is monitored throughout the year by program directors, labo-
ratory heads, and the fellows. Fellows are asked to present their research
findings at several informal meetings. All the fellows are invited to present
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APPENDIX F
115
findings at periodic formal dinners. Fellows are encouraged to apply for
research grants during their first year to fund future years of fellowship
research.
MEETING WITH PROGRAM MENTORS
The site visit team met with the laboratory mentors of the program:
David Hirsh, acting dean and chair, biochemistry and molecular biophys-
ics; Andrew Marks, director, Molecular Cardiology program; Lloyd
Greene, professor of pathology; Henry Ginsberg, director, Irving Center
for Clinical Research; Rudolph Leibel, chief, Division of Molecular Genet-
ics; Ira Tabas, professor of medicine; and Stephen Canfield, assistant pro-
fessor of medicine and former fellow.
Career Tracks fellows work very closely with a faculty mentor. The
mentor may be either basic science faculty or from a clinical department.
During the initial six months to one year the mentor may meet with the
fellow on a daily basis. Labs have typically six postdocs and a few gradu-
ate students and technicians, all of whom are resources for the fellow.
Fellows work on a wide range of projects in order to develop skills before
deciding on their particular research project. In some cases fellows take
on very ambitious projects, requiring substantial funding for equipment
and supplies, such as computers and mice.
The mentors agreed that training someone in basic research is like an
apprenticeship and that the mentor/fellow relationship is very impor-
tant. The mentors stressed that because it is a training program and that
because the mentor is not paying for the training, the fellows are not
expected to produce results, as some externally funded grants require.
Finally, the mentors stated that because the Career Tracks program guar-
antees up to two years of funding, there is less anxiety about transition
into the next phase of the fellows' career.
MEETING WITH MARKEY FELLOWS
Fellows who attended this meeting were Anthony Ferrante, Yi-Hao
Yu, Yi-ming Yang, and Stephen Canfield. The first three are current fel-
lows, and Dr. Canfield was a fellow in 1996-1997. The fellows overwhelm-
ingly felt that the program allowed them to pursue their research interests
rather than searching for a lab that had an open funding slot. All the
fellows attending the meeting plan to develop a career in academic medi-
cine and research.
The fellows all took different pathways to the basic research career
track. Three fellows had gone through an M.D. /Ph.D. program, although
one of them took off a year to serve as chief resident. One fellow had an
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6
APPENDIX F
undergraduate degree in physics and used that background to dovetail
his experience with his mentor's interest in development of quantitative
assays. This fellow's work was highly successful and culminated in the
development of a microarray facility at Columbia-P&S.
The fellows pointed out that the Markey award let them investigate
new and more interesting areas of research and blend their interests with
the resources at Columbia-P&S. This blending resulted from frequent
interaction between fellows and the program directors, who counseled
the fellows on potential mentors and directed the fellows to the mentors
who would best complement their interests and abilities.
FINANCIAL DATA
The original award was for $2 million. Markey funding for fellows
will continue through 2003. To date there has been a total of 25 years of
support for 15 fellows. The original cost per fellow was budgeted at
$47,520, including fringe, travel, and indirect costs. Because many of the
fellows have been able to obtain supplemental funding, the program has
actually spent less per fellow on average. University and program admin-
istration are fully committed to the continuation of the program.
SUMMARY
Although the Career Tracks program at Columbia-P&S is not the only
Markey program that offers research fellowships during the clinical house
staff experience—UCSF's Molecular Medicine program occurs at the same
point in training~olumbia-P&S is unique in its emphasis on career
counseling. Much time is spent on finding the right match of fellows and
lab directors so that the fellows feel confident in being able to further their
career in their chosen areas of research. A few of the fellows were placed
in non-Columbia labs because these labs were deemed the most appropri-
ate match for the fellow. Despite the excellent career counseling provided
by the program's codirectors, the level of mentorship was varied among
lab directors. Some fellows reported daily personal contact with their
mentors, while others reported sporadic contact, such as "when he needs
me, which is not that often." More emphasis on mentoring is an area
where the program could be strengthened.
The site visit team was impressed with the high quality of the struc-
ture and organization of Career Tracks program at Columbia-P&S. It was
clear that career counseling and placement of fellows in labs received
priority and the results have paid off. The level of sophistication of sev-
eral of the research projects has led to the acquisition of new equipment
that is currently used by several departments. At least one new patent
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APPENDIX F
117
application has resulted from the research of Markey fellows. Columbia-
P&S hired at least two fellows at the conclusion of their fellowships. A few
returned to clinical practice, which may be an indication of the burden-
some financial obligations facing young physician-scientists.
CHILDREN'S HOSPITAL BOSTON/HARVARD UNIVERSITY
THE MARKEY CHILD HEALTH RESEARCH CENTER
Philip Pizzo, the program director, stated that the most crucial period
in the development of the physician-scientist is the research fellowship
years. Those four years represent the "make or break" in the continuum.
Rapid, indeed, logarithmic growth must occur during this phase if the
physician-scientist is to put roots down firmly in biomedical science and
discover its application to relevant clinical problems.
This growth can occur only when aspiring physician-scientists have
the firm mentorship of more senior physician-scientists who have been
through the process, and will either guide the young persons in their own
laboratories or arrange a superb laboratory experience in the laboratory
of a close and cooperative colleague. It is this vital nexus between the
mentor and the aspiring physician-scientist that underlies this program.
The task of training program directors is to make the long road of training
financially feasible for young persons who are devoted to family as well
as to their profession. Above all, the scientific environment during those
crucial early years must be exceptional, requiring the cooperation of Ph.D.-
holding scientists and senior physician-scientists to create an ambiance
that will lead to success.
The pediatrician-scientist is perhaps more at risk than those in other
specialties. The number of students entering pediatric training has
dropped from 30 percent to 20 percent. Additionally, because women,
who make up about 80 percent of the pediatric workforce, have addi-
tional challenges that hinder them from pursuing a research career the
pediatric scientist enterprise must receive special consideration.
The mission of the Markey Child Health Research Center is to encour-
age, train, and develop the careers of young pediatrician investigators
through research development. The Markey award helped support young
pediatric investigators during a critical and vulnerable period in their
career development. Markey fellowships were awarded for one or two
years, with the goal being to obtain outside funding for research. If a
fellow was able to obtain adequate funding after the first year, Markey
funds were stopped.
A total of 17 fellows have rotated through the center. Most of these
fellows have M.D. degrees; only 3 have M.D./Ph.D. degrees. Eleven of
the fellows were funded for only one year, five fellows received two years
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118
APPENDIX F
of funding, and one fellow received three years of funding. Most fellows
were able to obtain grants or other fellowships, such as K-08 awards,
awards from Burroughs Wellcome, Howard Hughes Medical Institute, or
R-01 awards from He NIH.
MEETING WITH PROGRAM FACULTY AND CLINICAL
MENTORS
The site visit team met with the program's lab directors and mentors:
David Nathan, the originator of the Markey Child Health Research Cen-
ter; Steve Harrison, codirector of the program; Allen Walker; Joseph
Majzow; Lou Kunkel; and Merton Benfield. These mentors emphasized
that time for training and research is critical and that the Markey award
gave these young faculty members that protected time. Generally, for
M.D.s the greater the amount of protected time for research, the higher
the probability of that M.D. receiving an NIH R-01 grant. If the young
scientists are cast off too early, their careers never fully develop. Longer
training in one place is better than multiple, shorter periods of training.
Longer time in training enhances the ability to complete research projects
and to publish based on this bottom-line research productivity. This is the
typical model of graduate education in U.S. institutions. In comparison,
graduate students in Great Britain tend to publish whatever findings they
may have at the end of their three to four years in the lab. This is why, the
mentors believe, there is a need for four or more years of protected re-
search time. A critical mass is important to generate good research. De-
partments or labs that are too small may have a greater difficulty in achiev-
ing success.
The mentors agreed that one of the strengths of Markey was its ap-
proach of identifying programs and institutions with a proven track rec-
ord and providing them with substantial funding, generally without re-
strictions. The mentors believed that by allowing the institution to
determine who received a grant the mentors were able to choose indi-
viduals who they knew would do well. The selection process allowed the
mentors to use intangible criteria to identify fellows based on prediction
of success. Markey's flexibility in funding the program instead of indi-
viduals was very important. The Markey approach could only succeed
with private foundations; in fact, the Doris Duke Foundation is probably
going to follow this same principle. The K-08 award process is more risky
because it funds individuals rather than awarding funds to the program
and letting the program staff identify candidates. The mentors believed
that this approach might fund those who are less likely to be successful.
One solution, the mentors believed, was increasing national funding for
training programs in biomedical research for young physicians.
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APPENDIX F
119
The mentors agreed that the Markey fellows probably would have
done well without the Markey funding but that many of them would
probably have had to leave Harvard because of the high cost of living in
the Harvard and Boston area. Additionally, the Markey funds allowed
other resources to be directed to the so-called second-tier scholars who
provide support in the labs.
MEETING WITH MARKEY FELLOWS
Fellows attending the site visit were Maureen Jonas, Jordan Kreidberg,
Athos Bousvarios, Christina Luedke, Ellis Neufield, Garey Silverman, Dan
Nigrin, and Robert Husson. Most of the fellows reported that Markey
funds allowed them to concentrate their time and effort on obtaining
external funding. For example, Maureen Jonas was a full-time clinical
physician in hepatitis. She had been out of training for quite a while and
may have been less competitive in a grant proposal. Markey provided
time to develop a large, multicentered trial for which she received an NIH
grant. Dan Nigrin conducts research in bioinformatics, which does not fit
into regular NIH funding categories; the Markey funds gave him time to
craft a successful NIH grant proposal. Robert Husson had been develop-
ing new techniques for a new knockout mouse; therefore he did not have
much to show for his time in fellowship. The Markey funds provided a
bridge year so that he could publish and then obtain a K-08 grant.
The fellows had a limited awareness of the Markey Trust and its
mission. They never met as a group and had little awareness of other
Markey fellows in their program. They did express the desire to have
more of a Markey cohort for exchange of ideas and fellowship.
FINANCIAL DATA
The site visit team met with Bill New, who is the financial administra-
tor for Children's Hospital, Boston. The total research budget for Chil-
dren's Hospital is $100 million, including indirect costs. Because much of
the research funding floes not include overhead, 30-40 percent of actual
funding is lost. He reported that the $2 million Markey program resulted
in a $750,000 loss to Children's Hospital. The hospital is freestanding and
receives no support for graduate medical education. The hospital lost $61
million last year.
Perhaps most importantly, the Markey funds have been exhausted.
Children's Hospital set aside a portion of a $25 million endowment so
that the program could continue. Because of other budget priorities, that
set-aside is now being used to recruit new senior faculty.
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APPENDIX F
SUMMARY
The Markey Child Health Research Center is a powerful resource for
young investigators who need assistance in obtaining external research
funding. The site visit team was impressed with the caliber of the Markey
fellows and their research at Children's Hospital, Boston. The team found
five emerging themes during its visit.
1. The funding of institutional programs is much more valuable than
funding individuals.
2. The interdisciplinary culture of the institution is very important.
Much credit is given to Dr. Stephen Harrison and his vision for his lab.
3. Time spent on research is critical. Four or more years in the same
place are needed for successful research career development.
4. The K-08 award process is not very reliable or a good predictor of
success. Consistent programmatic funding allows for better planning.
5. Children's teaching hospitals face special fiscal constraints, as they
do not fully participate in Medicare funding for physician training.
Representative terms from entire chapter:
site visit
