Proceedings of a conference sponsored by the American Cancer Society, the Burroughs Wellcome Fund, and the Howard Hughes Medical Institute

February 2000

The Role

of the

Private

Sector in

Training

the Next

Generation

of Biomedical

Scientists

Biology in the postgenomic era will require individuals with new sets of skillswho can establish themselves successfully in rapidly moving fields of

research. Philanthropy has played and will continue to play an important part injump-starting the careers of new investigators, particularly during the transitionfrom postdoctoral fellow to faculty member, and in building bridges betweentraditional and emerging fields of research. The receipt of funding from aprestigious foundation, health agency, or medical research organization can bethe push that launches a research career. In addition, because the mission ofphilanthropy is often problem based, private funds can support inherentlyinterdisciplinary research and training that breaks new ground.

Although the magnitude of private contributions to biomedical researchtraining cannot match that of the federal government, philanthropy plays aspecial role. Foundations can complement public programs to realize a sub-stantial impact. In addition, they can support alliances that typically would notbe supported through public mechanisms. Private philanthropies, particularlyvoluntary health agencies with a disease focus, can provide critical help to fill the gap between the rate of advance in research and the translation of new knowledge into therapies for human disease. Private funders can use their resources to encourage beginning investigators to enter a research areacritical to the agency’s mission or to encourage midcareer investigators tochange course in their area of research focus.

We sponsored and convened this conference to explore in depth the uniquecontribution private funders can make to ensure that appropriate and adequatetraining programs are available for basic and clinical research. Two years ago,in February 1998, we convened a successful first meeting on this topic andsubsequently determined that an ongoing dialogue in the private fundingcommunity was a most useful step toward achieving an objective important toall those invited—ensuring that future biomedical research questions can beanswered by a well-prepared cadre of basic and clinical scientists.

We believe this gathering met our goals. Participants formed new relation-ships with other private funders and considered new directions in which theymight take their own organizations. The conference reinforced our belief thatprivate funds can change the culture and structures of research and education,not merely supplement the substantial investment made by the public sector.Because some of the most exciting work of the postgenomic era will occur atthe interface of disciplines, private funders can provide the “glue” needed tocompel faculty to work together toward research and educational goals.Importantly, the private sector can search for the right niche and experimentwith innovative approaches.

This report summarizes the meeting and is intended to provide similar stimulifor those who were unable to attend. It is our hope that the philanthropiccommunity will continue the many conversations that were initiated at this conference.

Thomas R. Cech, Ph.D.PresidentHoward Hughes Medical Institute

Enriqueta C. Bond, Ph.D.PresidentBurroughs Wellcome Fund

John Stevens, M.D.Vice President for Extramural GrantsAmerican Cancer Society

O

Letter

from the

Co-Sponsors

1

ExecutiveSummary

On February 14-16, 2000, the American Cancer Society, the Burroughs

Wellcome Fund, and the Howard Hughes Medical Institute convened

a meeting on private sector support for biomedical research training. The

goal of the meeting was to address the unique contribution that private

funders can make in ensuring that appropriate and adequate training

programs are available for basic and clinical research. Representatives from

government, academia, and nongovernmental funding agencies had the

opportunity to hear presentations and discuss current programs and plans

of public and private funders and to consider goals for the future.

The meeting focused on training two groups of future investigators: basic

biomedical and clinical scientists. In addition, cross-cutting topics were

addressed, such as the move toward electronic grantsmaking and ethical

issues facing future biomedical research.

Conclusions and Recommendations for Training of Basic Biomedical Scientists

Out of the sessions on training basic biomedical scientists emerged the

following conclusions and recommendations:

1. In the postgenomic era of research, multidisciplinary and interdis-

ciplinary research will command center stage, requiring team

approaches and the collaboration of many individuals from vastly differ-

ent fields, ranging from computational mathematics to clinical science.

2

2. The need for team approaches to scien-

tific research suggests that private fun-

ders can make a significant difference in

building expertise and collaborations by

providing support to clusters of faculty.

3. Support of postdoctoral students and

new faculty is important, but insufficient.

Philanthropy must also invest in the

development of scientists from under-

represented groups, provide appropri-

ate support for foreign students, and

recognize that with the globalization of

the research enterprise, it will be vital to

provide experiences for U.S. students

abroad.

4. The changing paradigm of research calls

for innovations and changes in the edu-

cation of scientists along the spectrum

of K-12, undergraduate, and graduate

education. The increasing need to value

teaching in all settings could be im-

proved by making grants that help

free the time of scholar/researchers for

teaching.

5. The private sector can facilitate some

areas or types of research more easily

than can public agencies. This would

include, for example, research with

embryonic stem cells or prehypothesis-

driven work to assemble and organize

information that can provide a platform

for hypothesis-driven work and infra-

structure support.

6. Partnerships among private funders

and between the public and private

sector will be valuable in moving the

postgenomic research and training

agenda forward and in leveraging the

investments of both private sector and

public sector groups.

Conclusions and Recommendations for Training of ClinicalResearchersThe genetic revolution and other scientific

advances are providing vast new and exciting

opportunities in clinical research. Investments

to advance the training of clinical researchers

were proposed in two major areas—human

capital and training programs.

1. The development of clinical scientists is a good target for private support. Aswith training basic scientists, it is critically important to support young clinical scientists, although other steps in the ladder also require attention.Research experiences during medicalschool, modeled after programs such as the Howard Hughes Medical Institute-National Institutes of Health (NIH) Cloister Program and the NIH-PfizerClinical Research Training Program, areexcellent examples of support of clini-cal investigators early in their careers.

2. The M.D.-Ph.D. is the most successfulmodel for the development of clinical scientists. This paradigm should be supported by the private sector in orderto expand the numbers of trainees atcurrently funded sites or to developnew programs at institutions that couldthen become eligible for NIH support.

3. Despite the predominance of the M.D.-Ph.D. scientist, there are other essentialtypes of physician-scientists, and thesescientists require different types of support.

• Numerous new master’s-level pro-grams are in development for clinicalresearch training. The private sectorcan make a contribution by assistingwith tuition support.

Executive Summary 3

• Ph.D.s, if trained in pathobiology or

other human disease constructs, can

provide an invaluable resource to the

clinical research team.

4. Transition support to assist individuals at

key points in their training and career

development, such as between thesis

work and the first independent faculty

position, can be essential to prevent

young scientists from leaving research.

In this respect, debt relief is crucial.

5. The development of multidisciplinary

and generic training programs in clini-

cal research is urgently needed, and

the collaboration of disease-oriented

groups could make a critical difference.

Such a consortium could provide funds

for junior faculty and graduate students

as they make key education and career

transitions.

6. The private sector could support innov-

ative mechanisms by which to develop

and support mentorship skills in new

and existing faculty.

At the meeting’s end, several private

funders agreed to pursue a joint project or

collaboration in some specific area where

organizations share a need and desired

outcome. Possible collaborations include

1) pilot programs to enhance the supply

of clinical investigators (Ph.D. or M.D.);

2) institutional training programs that break

down departmental barriers and promote

new models for training; 3) loan repayment

programs to entice M.D.s to continue in re-

search; and 4) career development programs.

4

Training BasicScientists for thePostgenomic Era

In a field moving as rapidly as biomedical science, it is difficult to predict which

skills are required of today’s scientists, let alone those that will be necessary for

the next generation. A survey of the existing landscape, however, provides a

sense of the directions in which science is headed.

In his keynote speech, David Botstein, Professor and Chairman in the Depart-

ment of Genetics at Stanford University, provided a perspective that is both invig-

orating and demanding. In the new world of genomics, scientists are at the

beginning of a journey that will lead to the eventual understanding of every human

protein and its role both in health and disease. As the Human Genome Project

reaches completion—resulting in a complete map of the human genetic code—

the next challenge will be to identify the functions of the genes that have been

mapped, the proteins for which they code, and the functions of those proteins in

the body.

Such information will move the practice of medicine in the direction of pre-

vention and treatment based on molecular makeups. Initially, discovering how

health depends on single mutations (genotypic features) and single proteins

(phenotypic features) will be relatively straightforward. For example, it may in-

volve understanding how single nucleotide polymorphisms (SNPs) are related to

how cancers develop and ways in which we can diagnose disease and tailor

medications. With time, however, more intricate relationships likely will be

discovered through population-based studies, entailing the generation,

storage, and analysis of enormous quantities of epidemiologic, genotypic, and

phenotypic data.

The immense amount of information generated by the Human Genome Project

is stimulating new collaborations between the traditional sciences of biology and

chemistry and the fields of bioinformatics, computer science, and mathematics.

In the words of Botstein, “When you are work-ing with 750 megabytes of biological informa-tion, computational power is not optional, it isnecessary. Without a computer we cannot doanything with the human genome.”

Botstein predicts that scientists will spendthe next 20 years figuring out the significanceand relationships of the human genome map.To understand the similarities and differencesamong organisms and between species,sophisticated comparisons must be con-ducted, and these comparisons cannot bedone by hand or by eye. Advanced bioinfor-matics, combined with well-designed data-bases and powerful computers, is providing aview of the relationships among organismsthat are sometimes separated in evolution bybillions of years, and computers can displaypatterns and periodicity that would never befound if searched for manually. Said Botstein,“Computers allow us to make discoveries onwhich we can base beautiful hypotheses thatcan then be tested.”

Molecular biologists and biochemists havedeveloped a variety of laboratory-basedassays that are powerful and readily adapt-able to large-scale efforts. Engineers havedeveloped innovative robotic and automationtechnologies that are capable of skyrocketingthe number and variety of laboratory experi-ments. Computer scientists have developedprogramming languages and database man-agement systems that have provided thebasic building blocks for improved environ-ments for scientific collaboration. And physi-cists (driven by the need to share the largeamounts of data generated in high-energy par-ticle physics) have catalyzed the development

of the Internet, which is literally transformingthe ways in which scientific and technical collaborations take place.

Never before have biologists been facedwith so much data, and never has the need toorganize the data been greater. Bioinformaticsprovides a common language for many disci-plines, an essential element for applying thewisdom of biology, chemistry, physics, andmathematics to a problem. The beauty of theintegration of biology and information science,claims Botstein, is the ability to make discov-eries ex post facto from the computer. “Wecannot get to where we need to go using afrontal assault based on biology alone,” saidBotstein. “We are in the genomic revolution, in

Training Basic Scientists for the Postgenomic Era 5

“Computers allow us to make discoveries onwhich we can base beautiful hypotheses thatcan then be tested.”

David BotsteinStanford University

Changing Paradigms in Basic Biology■ High-throughput technologies may be

regarded as an enabling technology for modern biology.

■ Databases and biological repositories areessential facilities.

■ Sequence databases are revolutionizing theway we study the structure and function ofbiomolecules and cells.

■ Sequence data provide powerful insights intoevolutionary relationships and biodiversity.

■ Genomic information will be essential for understanding biocomplexity in theenvironment.

Mary Clutter, National Science Foundation

6

which we must figure out a system that makessense, use bioinformatics to support the sys-tem, develop a clear language about the dataand the outcomes, produce a suitable displaysystem, and apply all this to clinical samplesthat were saved in a useful and informativeway.”

On the “digital” side, researchers havegrowing access to supercomputers that per-form millions of operations per second, Internetbackbones that transmit 109 bits of informationper second, and databases that contain 1015

bits of information. Thus, more than ever, newtools and technologies from engineering, com-puter science, mathematics, chemistry, andphysics hold great promise for tackling scien-tific challenges in medicine and biology.

So, How Do We Get Therefrom Here?In the postgenomic era of research, multidis-ciplinary and interdisciplinary research willcommand center stage, and some of the mostinteresting research will take place at theboundaries of disciplines and from combiningknowledge from various fields. This requiresteam approaches and the collaboration ofmultiple individuals from vastly different fields,such as computational mathematics andclinical research.

This is not to say that there is no longerroom for the specialist. In many cases, con-centrated work in a single discipline willremain the best way to advance the develop-ment of knowledge. However, basic scientistsworking together from more than one discipli-nary vantage point can advance fundamentalknowledge in important ways that cannot beattained without such collaboration. This meansthat providing opportunities for students to workcollaboratively will be an increasingly impor-tant part of an education in science.

Good Teaching, Rich Classroom and LaboratoryExperiences, Mentoring,and Hard WorkWhat is the best way to educate an individualso that he or she develops the skills needed toconduct science in the postgenomic era?There is no simple or single solution, agreedparticipants, but there are many good models.David Botstein talked about the importance ofgood teaching and the necessity of today’sseasoned scientists to return to the classroom.He believes that many leading scientists areactively involved in interdisciplinary researchand thus serve as the best examples foraspiring young scientists.

Freeman Hrabowski, President, Universityof Maryland, Baltimore County, credits oneperson in particular for sparking the excite-ment of countless minority students who havegone on to careers in science. “Mike Summers,a Professor of Chemistry and Biochemistryand Adjunct Professor of Biological Chemistry,brings joy to his teaching,” said Hrabowski.“He is a true mentor and is singularly respon-sible for my campus sending more minoritystudents on to graduate school in the sciencesthan any other institution.”

Hrabowski emphasized the need forpatience and said that many students, espe-cially those from minority populations, come to college unprepared. “This doesn’t mean it’sover for them,” he commented. “It just meanswe need to work with them, even if it meanstaking a course twice to get it right.” And, headded, educational institutions have to getbeyond what he calls the “deficit model” ofteaching. Not all minority students fall into thecategory of remediation, and some studentswho are superbly talented are not recog-nized because of the narrowness of our view.“How do you promote minority students in science education?” Hrabowksi challenged.“You find the best students, insist on a culture

that encourages the best faculty to beinvolved, get the students connected toresearch, provide environments for group workacross disciplines, and make them repeat theircourses until they are ready to move on.” Botstein noted that the entire educational system would be more effective if Hrabowski’sapproach were adopted for all students.

In terms of formal training, students musthave adequate breadth in both instruction and laboratory experiences, said NicholasCozzarelli, Professor in the Division of Bio-chemistry and Molecular Biology, University ofCalifornia-Berkeley. Cozzarelli routinely askshis students to be open-minded, to take

chances, and to be prepared for facing multiple options. There is nothing wrong withspecialization, added Botstein. Our academicstructures are quite good at producing spe-cialists, he noted, but these specialists musthave “sockets” so they can communicate withothers with different training and focus.Nonetheless, these specialists need sufficientexposure to a broad range of other specialties,or cross exposure, so that they are able to

Training Basic Scientists for the Postgenomic Era 7

“How do you promoteminority students in science education?”Hrabowksi challenged.“You find the best students, insist on a culture that encouragesthe best faculty to beinvolved, get the students connected to research, provideenvironments for groupwork across disciplines,and make them repeattheir courses until theyare ready to move on.”

Freeman HrabowskiUniversity of Maryland, Baltimore County

The David and Lucile Packard Foundation:Changing the Culture by Example

Historically Black Colleges and Universities Science ProgramTo improve the teaching of science at historicallyblack colleges and universities (HBCUs), the Packard Foundation invites proposals annually from a selected set of HBCUs and awards grants totalingapproximately $2 million. The goal of this program is to increase the number of young black graduatesqualified in science who can become leaders in theirfields and role models for the next generation of students. An advisory panel of eminent black educators assists Foundation staff members in setting guidelines and evaluating proposals.

Tribal Colleges Science Program Often overlooked by the general population, tribalcolleges are now being recognized as an importantpart of the educational landscape in America. Theseare mostly community colleges founded by AmericanIndians and located on or near reservations in mid-western and western states. The goal of the TribalColleges Science Program is to help tribal collegesbetter serve the needs of students studying science.Grants totaling approximately $2 million are awardedannually. An advisory panel of experts who areactively involved in tribal colleges assists Foundationstaff members in evaluating proposals and monitoringgrants in this area.

8

realize when they have reached their limita-tions and should seek help. To illustrate theneed for cross exposure, Thomas Cech, President, Howard Hughes Medical Institute,quoted biologist Lewis Thomas, who wrote

If you want a bee to make honey, you donot issue protocols on solar navigation orcarbohydrate chemistry, you put himtogether with other bees....And you dowhat you can to arrange the generalenvironment around the hive. If the air isright, the science will come in its ownseason, like pure honey.

Stephen Burley, Rockefeller University,described the Burroughs Wellcome FundInterfaces Training Program, which aims tocreate an environment in which “cross- pollination” can occur. The Program has aunique structure. It has no formal departmentsand 75 faculty in chemistry, physics, and biology who report to the president. Two centers—one in physics and biology and onein chemistry and biology—comprise collec-tions of faculty with common interests, whoconduct collaborative research and training.The long-term goal of this approach is to bringquantitative tools to bear on problems in biology. Burley admits that this strategy islikely to increase the training time of new scientists.

Cech suggested that to understand train-ing and career models that work, we shouldlook to the common denominators in the training of individuals who have successfulcareers as interdisciplinary scientists workingwith teams of diverse individuals. He citedHoward Hughes Medical Institute Investi-gators Sharon Long, Stanford University,Stephen L. Mayo, California Institute of Technology, and Roderick MacKinnon, Rockefeller University, as exemplars of individuals trained in multiple disciplines who conduct interdisciplinary research.

Overcoming Barriers toInterdisciplinary Researchand Training in the BasicSciencesMany panelists cited the traditional and per-sistent barriers to interdisciplinary researchand training that must be addressed if post-genomic biomedical research is to reach itsfull potential. These include attitudinal resis-tance; differing research methodologies andcommunication barriers among disciplines;the length and depth of training in a single fieldthat is needed to develop scientists who willbe successful in competing for funds; the difficulty in forging a successful career pathoutside of the single-discipline structure;impediments to obtaining research funding forinterdisciplinary research early in one’s career;the scarcity of interdisciplinary departments inacademe; and the perceived lack of outlets forthe publication and dissemination of interdis-ciplinary research results.

Cozzarelli noted that it takes certain inter-personal skills to conduct interdisciplinaryresearch and that laboratory training alonemight not be sufficient to develop those skills.Moreover, interdisciplinary research teamsmust be led by individuals who understand thechallenges of group dynamics and who canprovide appropriate leadership.

Academic departments create the environ-ment within which education and researchoccur and often perpetuate disciplinary identity through training and mentoring practices, said Howard Hughes Medical Insti-tute’s Cech. This can inhibit interdisciplinaryresearch, because investigators intrigued bythe same multifaceted problem are likely towork in different departments. Moreover, pro-motion and tenure policies and practices,which serve as tremendous motivators andcontrolling devices for academic scientists,also are driven by departmental cultures. Inaddition, the priority given to contributions in

Training Basic Scientists for the Postgenomic Era

Sharon R. Long, Ph.D. Dr. Long, a Howard Hughes Medical InstituteInvestigator, is also Professor of Biological Sciences at Stanford University and Adjunct Pro-fessor of Biochemistry at Stanford UniversitySchool of Medicine. She received her B.S. degreefrom the California Institute of Technology, in theIndependent Studies Program, and her Ph.D.degree in cell and developmental biology fromYale University. Dr. Long has been awarded aMacArthur Prize fellowship and is a member of the National Academy of Sciences. She is a fellow of the American Academy of Arts and Sciences and the American Academy of Micro-biology. Her laboratory combines a number ofapproaches—including genetics, biochemistry,and cell biology—in the study of a symbiotic bacterium-plant association to ask how new celldivision, growth, and gene expression arise ineach partner due to stimulation from the other.Dr. Long’s team has identified and cloned thegenes in the bacterium that cause it to stimulatenodule formation in its host and has found thatthese genes are only expressed in the bacteriumwhen in the presence of a signal from the planthost root. This signal is a small molecule in the chemical category known as flavonoids.Flavonoids and related compounds have beenproposed to have health benefits as componentsof human diets, but no specific mechanisms havebeen established.

Stephen L. Mayo, Ph.D.Dr. Mayo is Assistant Professor of Biology at the California Institute of Technology andAdjunct Assistant Professor of Biochemistry andMolecular Biology at the University of Southern California School of Medicine, Los Angeles. He isa Howard Hughes Medical Institute AssistantInvestigator. Dr. Mayo received a B.S. degree inchemistry from Pennsylvania State University anda Ph.D. degree in chemistry from the CaliforniaInstitute of Technology, where he studied bio-logical electron transfer. Dr. Mayo developed arule-based molecular mechanics force field as

a Miller Fellow at the University of California,Berkeley, and studied hydrogen/deuterium exchangereactions in proteins as a postdoctoral fellow withRobert Baldwin at Stanford University School ofMedicine. Dr. Mayo is also a Rita Allen FoundationScholar, a Searle Scholar, and a Packard Fellow.His laboratory focuses on the coupling of theoret-ical, computational, and experimental approachesfor the study of structural biology. In particular, hehas developed quantitative methods for proteindesign, with the goal of developing a systematicdesign strategy that is called protein designautomation.

Roderick MacKinnon, M.D.Dr. MacKinnon, a Howard Hughes Medical InstituteInvestigator, is also Professor of Molecular Neurobiology and Biophysics at Rockefeller University. He received a B.A. degree in biochemistry from Brandeis University and anM.D. degree from Tufts University School of Medicine. He completed a medical residency atBeth Israel Hospital, Harvard Medical School, andpostdoctoral work at Brandeis. Dr. MacKinnonhas received the Young Investigator Award fromthe Biophysical Society and the prestigious 1999Albert Lasker Medical Research Award. His workfocuses on ion channels, membrane-spanningproteins that form a pathway for the flow of inor-ganic ions across cell membranes. Ion channelsare extraordinarily simple physical systems, andyet they are responsible for all electrical signalingin biology. Among their many functions, ionchannels control the pace of the heart, regulatethe secretion of hormones into the bloodstream,and generate the electrical impulses underlyinginformation transfer in the nervous system. Dr. MacKinnon’s laboratory relied on molecularbiological and electrophysiological techniques,but when the lack of molecular structure limitedtheir progress, they embraced the distant field ofx-ray crystallography. The result was a much-heralded atomic-level photo of the potassium ionchannel.

9

The Face of Modern Biomedical Research: Interdisciplinary Investigation Conducted with Public and Private Support

10

areas recognized by departmental struc-tures may fail to nurture interdisciplinaryapproaches.

Departmental chairs are generally recruitedor appointed because they are outstandingexamples of the discipline that is representedby the department. It may be difficult, there-fore, for junior faculty whose interests rangebeyond the formal subject matter of a givendepartment to be viewed as either makingsubstantial contributions to the field or as meriting advancement in a given department.

The issues surrounding disciplinary identitycan spill over into training. Current depart-mental structures, particularly the lack ofmechanisms for mentoring in specific trainingprograms, may restrain the development of interdisciplinary researchers. With theincreased competition for research funds,many departments have developed modelsfor mentoring junior faculty, both in the grant-writing process and in obtaining hands-onresearch experience early in projects. But alltoo often, junior investigators in a departmentare limited to mentoring or training opportuni-ties provided by the faculty of that department.

Finally, a scientist’s research reputation isessential to obtaining research support, gain-ing employment, getting promotions, and win-ning grants. Authorship on papers is perhapsthe single most important predictor of one’ssuccess in these areas. In the past, the size of collaborative groups has posed problems for interdisciplinary researchers, particularlywhen it came to listing authors on publications.Fortunately, this trend is reversing. However,the important contributions of those who historically have been considered the “hand-maidens” or technical support in large in-terdisciplinary efforts (computer scientists,statisticians) are still often under-recognized.

Until more academic departments are will-ing to acknowledge individual contributions to an interdisciplinary research effort, ratherthan author position on a journal article, younginvestigators will be dissuaded from engagingin interdisciplinary research with multiple

collaborators. That “luxury” will be reserved for the tenured professor who has alreadyestablished a research career.

Private Funders Making a DifferenceWith the strong economy of the past decade,new philanthropic efforts have emerged. Totalannual giving by over 44,000 foundations is estimated to be more than $20 billion. Thescientific share of philanthropy, however, is notincreasing, reported Jaleh Daie, Director ofScience Programs at the David and LucilePackard Foundation, who noted that onlyabout 300 foundations regularly support science.

Even though the private contribution cannotmatch that of the federal government, saidDaie, philanthropy plays a special role. Foun-dations can leverage off of public programs to realize a substantial impact. Private giverscan catalyze innovation by jump-startingemerging fields, she added. In addition, theycan support alliances that typically would notbe supported through public mechanisms.Perhaps one of the most rewarding roles ofphilanthropy, said Daie, is to “prime the pump”by supporting young investigators at thebeginning of their careers.

Investing in the Future

Philanthropic organizations have long madecritical contributions to support the earlycareers of basic scientists. The importanceof private support of young investigatorswas emphasized by Donella Wilson,National Scientific Program Director for theAmerican Cancer Society, which spends$100 million annually on research awardprograms that are peer reviewed by externalcommittees. In recent years, an oversightgroup has recommended that the Societyrefocus its research awards on beginninginvestigators to help them become securelyestablished.

Similarly, the American Heart Associationhas carved an important niche in supportingthe development of beginning investigatorsand offering innovative funding mechanismsto stimulate research in promising scienceareas, reported Susan Barnett, Vice Presi-dent of Research Administration. Althoughthe federal government provides more moneyfor research through the National Heart,Lung, and Blood Institute, National Institutesof Health (NIH), the Association makes a sub-stantial contribution in a more focused way. In1999, it spent $130 million on research,received more than 3,000 applications, andfunded 1,000 awards. Of this, $64 million wasdedicated to beginning investigators (notmore than four years from first facultyappointment).

The Association also supports the careerdevelopment of highly promising clinician-scientists and Ph.D.s who have recentlyacquired independent status. This is done byencouraging and adequately funding high-quality, innovative research projects for whichfinancial support has not been previouslyobtained from any other agency.

The same is true for the W.M. Keck Foun-dation, through its Distinguished YoungScholars in Medical Research Program. ThisProgram is designed to promote the earlycareer development of a select group of thecountry’s brightest young biomedical scien-tists. It supports groundbreaking researchaddressing the fundamental mechanisms ofhuman disease by young investigators whoexhibit extraordinary promise for independentbasic biological and medical research andwho demonstrate a capacity for future acade-mic leadership.

According to Maria Pellegrini, Keck ProgramDirector for Science Engineering and the Lib-eral Arts, the Foundation invites 30 outstand-ing research universities and independentresearch institutes annually each to nominateone faculty member who is in the second to

Training Basic Scientists for the Postgenomic Era 11

The Keck Graduate Institute of Applied Life Sciences: Supporting“Good Human Protoplasm”

Launched in 1997 with a $50 million founding grant from the W.M. Keck Foundation, the KeckGraduate Institute of Applied Life Sciences is thefirst graduate school in the country solely dedicatedto the marriage of the life sciences and the subdis-ciplines of engineering. Reflecting the significance—and potential—of this endeavor, this is the secondlargest grant ever made by the Foundation for a single project.

The Keck Graduate Institute of Applied Life Sciences seeks to build on the profound insightsinto the understanding of biological processes nowemanating from corporate and government researchlaboratories and to play a central role in translatingthe vast potential of these discoveries into practicalapplications by preparing a uniquely qualified classof professionals for responsible and productivecareers in life science-based organizations. In thewords of Maria Pellegrini, Program Director, the goal is to support “good human protoplasm.”

Specifically, the Graduate Institute will focus initially on three or four “niches” where it can build distinctive competencies. These areas of concentration, which will be chosen from amongsuch fields as biochemical process engineering, bio-instrumentation, biomaterials, medical devices,bioinformatics, and biomechanics, will be comple-mentary to one another and will have strong cross-linkages with regard to research opportunities,industrial interests, and curricular requirements.

A particular feature of the Graduate Institute will be its emphasis on giving students a full understanding of the climate and culture in whichscientists and technologists in industry must func-tion. Accordingly, instruction in management,ethics, economics, systems, and policy issues, aswell as substantial team-based project work, will be central to the curriculum.

12

fourth year of his or her first tenure track posi-tion. Up to five recipient institutions receive a maximum of $1 million each. These grantssupport the research activities of the selectedcandidates for a period of up to five years andenable the institution to purchase necessaryequipment and resources to facilitate theinvestigative process.

The Keck Foundation’s goal is to providethese institutions and their young scientistswith the opportunity to investigate promisingand unproven new ideas for which fundingcan be difficult to obtain, even for establishedresearchers with steady funding streams.Pellegrini emphasized that these awards arenot intended to remove these scientists fromthe academic environment or to relieve themof their teaching responsibilities and the grant-writing and administrative burdens ofrunning a laboratory, all of which the Founda-tion believes are important parts of everyyoung scientist’s training.

Targeting Research

In addition to supporting new investigatorswhile they establish their research careers,philanthropy can target areas of research thatare not supported or that are underfunded.This is particularly true for voluntary healthagencies, which have targeted missions andtangible goals.

For example, the Juvenile Diabetes Foun-dation makes a crucial contribution by focus-ing on research that has the promise ofproducing a cure for Type I diabetes. A sec-ondary outcome of research support is thetraining of new investigators in research that is important to the Foundation’s mission. To

illustrate, since September 1998, the Founda-tion has funded nine new research centers—large-scale, multidisciplinary, high-priorityinitiatives that are focusing on solving spe-cific problems within the three priority goalareas: 1) restoration of normal blood sugarlevels; 2) avoidance of and improved treat-ment for complications; and 3) prevention ofdiabetes and its recurrence. Through the initi-ation of human clinical trials, the centers willuse the expanded diabetes knowledge baseto move research out of the laboratory and intothe lives of those with diabetes.

Robert Goldstein, the Foundation’s ChiefScientific Officer, emphasized that the goal ofthe Foundation, and of organizations like it, isto commission scientists to solve a problem,such as islet cell transplantation. “We recog-nize that training is a component of that goal, if not the primary goal," he added.

The American Heart Association’s Barnettalso commented on the targeted approach toresearch funding. For example, this year theAssociation set specific content goals for itsresearch program, including patient care andoutcomes research, brain blood vessel biol-ogy, functional genomics, and stem cellorganogenesis.

Many voluntary health agencies rely on layreviewers of research to help them meet theirgoals. The Juvenile Diabetes Foundation’sGoldstein noted that the lay review conductedafter scientific review adds a valuable compo-nent to research evaluation. He added that theFoundation adopts a proactive approach tothe scientific research community by introduc-ing early in the process the priority problems itwants to address using a flexible, fast-track

“There are times when the interests and goals of voluntary health groups and federalfunders overlap and collaboration is in order.” Robert Goldstein

Juvenile Diabetes Foundation

review of applications for research projects.Not all voluntary health agencies have theresources to conduct rigorous peer review of protocols. The Life Sciences ResearchFoundation supports an annual postdoctoralfellowship program, which provides built-inpeer review for funders, at no additional cost.Juried by a panel of Nobel laureates and otherdistinguished scientists, these fellowships arehighly competitive and have been offeredsince 1983. Dr. Donald Brown, Life SciencesResearch Foundation President, said the

Foundation provides a cost-effective way forfunders to support research training.

Collaborating with Public Funders

Although it is rare, some private funders haveentered into productive collaborations withfederal funders. For example, from 1986 to1998, the Alfred P. Sloan Foundation providedsupport for research in molecular evolution.Beginning in 1994, the Foundation operated ajointly sponsored program with the NationalScience Foundation in this area, consisting of

Training Basic Scientists for the Postgenomic Era 13

Progress in Electronic GrantsmakingDr. Joseph Perpich, Vice President for Grants and Special Programs, Howard Hughes MedicalInstitute, invited participants to share their ideas and views regarding the “new world of electronic grantsmaking” and introduced a panel of representatives of several funders of bio-medical research training that have undertaken the development of Web-based systems forelectronic grantsmaking. (See also Appendix A.)

Ellis Rubinstein of the American Association for the Advancement of Science discussednew enhancements that have been made to the Association’s successful online database andcareer development sites, GrantsNet and NextWave, and T. J. Koerner, Director of ResearchInformation Management at the American Cancer Society, Carolyn Miller, Director of the FastLane Project, the National Science Foundation, and George Stone, Chief of the Commons, Extramural Inventions and Technology Resources Branch, NIH, demonstratedtheir online grant application systems and talked about current and future challenges andopportunities in the area of electronic grantsmaking. Participants agreed that the four systems created by these funders clearly demonstrate the value of Web-based systems forhandling applications and grants online and the benefits of sharing data.

Dr. Perpich provided an overview of the Howard Hughes Medical Institute online physician-postdoctoral competition program and called participants’ attention to the Institute’s excitingnew virtual discussion forum (www.hhmi.org/grants/forums.htm). With a section devotedto topics in electronic grantsmaking, as well as one on general grantsmaking issues, the virtual forum will provide both public and private funders of biomedical research trainingwith an opportunity to explore a variety of issues, including the use of current and develop-ing technologies in data sharing among multiple systems that have not been built aroundcommon data fields.

In opening remarks, Enriqueta Bond, President of the Burroughs Wellcome Fund, alsofocused on the importance of sharing information, commenting that it is clear that privatefunders can be more strategic about their investments if they know what others are doingand have an understanding of current trends, challenges, and opportunities, including those for partnerships. John Stevens, interim Strategic Business Manager for the AmericanCancer Society’s Research and Health Professional Training Program and Vice President forExtramural Grants, added that the meeting is a critical component in spreading the wordabout what grants are available and ways in which individuals can apply for those awards.

14

two parts: a Postdoctoral Research Fellow-ship, which provided 18 awards per year fortwo-year postdoctoral fellowships, and aYoung Investigators Program, which providedawards of $100,000 to five applicants in thefirst few years of their independent researchcareers.

The Alfred P. Sloan Foundation also has collaborated with the U.S. Department ofEnergy (DOE), reported Program DirectorMichael Teitelbaum. In 1995, the Foundationapproved a Postdoctoral Fellowship Programin Computational Molecular Biology, jointlysponsored with the Office of Health and Environmental Research of DOE, to supportup to 10 postdoctoral fellowships each year.The Program is aimed at catalyzing career transitions into computational molecular biologyfrom physics, mathematics, computer science,chemistry, and related fields. Teitelbaum saidthe programs have worked well, as long as the funds contributed by each donor are keptseparate.

Programs of Federal FundersSeveral federal funders provide critical trainingsupport for basic biological and biomedicalscientists. Federal support tends to be broadbased rather than categorical, although sometraining grants can target specific areas ofresearch in which trainees can be supported.For example, the National Institute of GeneralMedical Science (NIGMS), NIH, providespredoctoral training grants in bioinformaticsand computational biology; biotechnology;cellular, biochemical, and molecular sciences;chemistry-biology interface; genetics; mole-cular biophysics; pharmacological sciences;

and systems and integrative biology, reportedMarvin Cassman, NIGMS Director.

The primary mechanism through which NIH supports predoctoral and postdoctoraltrainees and fellows is the National ResearchService Award. NIGMS and other NIH Institutesalso make awards to institutions for the train-ing of predoctoral students and postdoctoralresearchers. In addition, the NIH Medical Scientist Training Program (MSTP), leading tothe combined M.D.-Ph.D. degree, supportsthe integrated medical and graduate researchtraining that is required for the investigationof human diseases.

NIGMS’s goal in its predoctoral programs isto provide trainees with broad access toresearch opportunities across disciplinary anddepartmental lines while maintaining highstandards of depth and creativity. Cooperativeinvolvement of faculty members from severaldepartments or doctoral degree programs isone essential aspect of this multidisciplinaryemphasis. Another is breadth in researchtraining instruction, with regard to both the cur-riculum and laboratory rotations. Students aretypically supported by the NIGMS predoctoraltraining grant for one to three years of gradu-ate studies in Ph.D. programs or for two to sixyears in the M.D.-Ph.D. programs, and byother mechanisms in subsequent years. Therationale for this approach is that studentssupported by the training grant have greaterflexibility early in their studies in making crucialchoices about courses and research fields.However, the current stipend level for FY 2000for predoctoral trainees of $15,060 per year isfar too low, said Cassman.

The public sector historically has been animportant source of funds for training minorityscientists. For example, NIGMS participates in

The primary mechanism through which NIH supports predoctoral and postdoctoral trainees and

fellows is the National Research Service Award.

an NIH-wide program of individual predoctoralfellowship awards for minority students. Theseawards provide up to five years of support for research training leading to a Ph.D. orequivalent research degree, a combinedM.D.-Ph.D. degree, or another combined pro-fessional doctorate-research Ph.D. degree inthe biomedical or behavioral sciences. Eligiblefor this award are highly qualified studentswho are members of minority groups that are under-represented in the biomedical or behavioral sciences in the United States. Theintent of this fellowship program is to encour-age these students to seek graduate degrees,thus furthering the goal of increasing the number of minority scientists who are pre-pared to pursue careers in biomedical andbehavioral research.

John Ruffin, Associate Director for Researchon Minority Health, Office of the Director, NIH,noted that many programs aimed at minoritystudents are efforts to retain students who arealready interested in the sciences and that it isan important federal role to capture the interestof students who currently are not thinkingabout science. In response to these concerns,NIH offers its investigators supplements toattract under-represented minorities into bio-medical and behavioral research throughoutthe continuum from high school to the facultylevel. In addition, the Initiative for Minority Students: Bridges to the BaccalaureateDegree provides training that leads to the baccalaureate degree for selected studentsfrom under-represented minority groups. Theobjective is to encourage the development ofnew and innovative programs and the expan-sion of existing programs to improve the aca-demic competitiveness of under-representedminority students and to facilitate the transitionfrom two-year junior or community colleges tofour-year institutions.

Other NIH Institutes support training pro-grams of importance to their research portfolio.The National Human Genome Research Institute (NHGRI) has a small but targeted

program to support predoctoral and post-doctoral training in areas of importance to the NHGRI mission, such as the interfacesbetween biology and physics, reported ElkeJordan, NHGRI Deputy Director. NHGRI also supports numerous career developmentawards, such as the Genome Scholar Devel-opment and Faculty Transition Award, made topromising new genome researchers to estab-lish an independent research program ingenomic research and analysis and to securea tenure-track appointment in an academicinstitution in the United States.

Jordan also described NHGRI’s CurriculumDevelopment Award in Genomic Researchand Analysis, which supports the develop-ment of courses and curricula designed totrain interdisciplinary scientists who combineknowledge of genomics and geneticsresearch with expertise in computer sciences,mathematics, chemistry, physics, engineering,or closely related sciences. Jordan anticipatesthat these courses or curricula will be useful tostudents and scientists who wish to developnew conceptual approaches to genomeresearch and analysis or to organize, analyze,or interpret large data sets resulting fromgenomic and genetics research.

The National Science Foundation is anotherimportant supporter of training in the basicbiological sciences, but it also providesessential backing for education in mathe-matics, physics, and chemistry. Moreover, the Foundation historically has emphasizedthe integration of research and education,because, according to Assistant Director MaryClutter, “the best place to educate people is inthe discovery-rich environment of research.”

Training Basic Scientists for the Postgenomic Era 15

“The best place to educatepeople is in the discovery-richenvironment of research.”

Mary ClutterNational Science Foundation

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National Science Foundation programsinclude Research Experiences for Undergrad-uates, Collaborative Research at Under-graduate Institutions, Graduate Teaching Fellows in K-12 Education, Faculty EarlyCareer Development, and Postdoctoral Fellowships. An important new program, theIntegrative Graduate Education and ResearchTraineeship (IGERT) Program, was initiated in1997 to meet the challenges of educatingPh.D. scientists and engineers with the multi-disciplinary backgrounds and the technical,professional, and personal skills needed forthe career demands of the future.

The IGERT Program is intended to catalyzea cultural change in graduate education for students, faculty, and universities byestablishing new and innovative models forgraduate education in a fertile environmentfor collaborative research that transcends traditional disciplinary boundaries. It is alsointended to facilitate greater diversity in stu-dent participation and preparation and tocontribute to the development of a diverse,globally aware science and engineeringworkforce.

Goals for Private FundersBiology in the postgenomic era will requirenew sets of skills and individuals who canestablish themselves successfully in rapidlymoving fields of research. Clearly, philan-thropy has played and will continue to play animportant part in jump-starting the careers ofnew investigators, particularly during the transition from postdoctoral fellow to facultymember. The receipt of funding from an organ-ization such as the American Cancer Societyor the American Heart Association, for exam-ple, can be the push that launches a researchcareer. In addition, philanthropy, because itsmission is often problem based, can supportinherently interdisciplinary research and train-ing that breaks new ground.

Several meeting participants emphasizedthe value of private funds in trying to changethe culture and structures of research andeducation. Because some of the most excitingwork of the postgenomic era will occur at theinterface of disciplines, private funders canprovide the “glue” needed to force faculty towork together toward research and educa-tional goals. Private foundations can providefinancial incentives to institutions to changebehavior and to encourage scientists to teach.

Two currently funded American CancerSociety trainees, Anne Blackwood, M.D., andMichelle Tallquist, Ph.D., emphasized theneed for transitional training mechanisms toteach scientists how to move from being a student to becoming a successful facultymember; manage a laboratory; ensure contin-ued education; and receive departmentalcredit good toward professional promotionwhile engaging in interdisciplinary researchprojects. Also mentioned was a need for moregrant funding for junior faculty past the five-year faculty career mark, which should alsoprovide possible internship experiences foralternative career choices.

Unlike the public sector, because of its mission and more limited resources, privatefunders can be elitist, choosing the best stu-dents and developing them faster. Finally, theprivate sector frequently has the freedom totake chances and change directions quickly.

The following conclusions and recommen-dations emerged from the sessions on trainingbasic biomedical scientists:

1. In the postgenomic era of research, multidisciplinary and interdisciplinaryresearch will command center stage.Some of the most interesting researchwill take place at the boundaries of dis-ciplines and from combining knowledgefrom different disciplines, requiring teamapproaches and the collaboration ofmany individuals from vastly differentfields, ranging from computational math-ematics to clinical science.

2. The need for team approaches to scien-tific research raises questions about howto invest private dollars to support suchwork beyond the center or programgrant approaches. Several examples ofpossible approaches to meeting thisgoal were cited, including providinggrants to support clusters of faculty inorder to build expertise and collabora-tions and establishing programs thatforce collaborative research.

3. The development of human capital witha set of new skills is essential. Support of postdoctoral students and new fac-ulty is important, but more is needed.Philanthropy must also invest in thedevelopment of scientists from under-represented groups, provide appropri-ate support for foreign students, andrecognize that with the globalization ofthe research enterprise, it will be vital toprovide experiences for U.S. studentsabroad.

4. The changing paradigm of researchcalls for innovations and changes in edu-cation of scientists along the spectrum of K-12, undergraduate education, andgraduate education. Some examplesidentified ranged from such simple inno-vations as requiring biology courses forall engineering students, to the develop-ment of a valued terminal master’sdegree in bioinformatics, to wholesalechanges in undergraduate education.The increasing need to value teaching in all settings could be improved by making grants that free the time ofscholar/researchers for teaching.

5. The private sector can facilitate someareas or types of research more easilythan can public agencies, such asresearch with embryonic stem cells orprehypothesis-driven work to assembleand organize information that can pro-vide a platform for hypothesis-drivenwork and infrastructure support.

6. The unfolding of the postgenomic eraraises many ethical issues that deserveconsideration and study as well as theestablishment of guidelines if privatesector support is considered for areas inwhich controversy exists.

7. Partnerships among private funders andbetween the public and private sectorwill be valuable in moving the post-genomic research and training agendaforward and in leveraging the invest-ments of both private sector and publicsector groups.

Training Basic Scientists for the Postgenomic Era 17

Supporting Beginning Cancer ResearchInvestigatorsThe American Cancer Society, a community-basedvolunteer health organization, is the largest source ofprivate, not-for-profit cancer research funds in theUnited States. A major focus of its research programis the support of cancer investigators early in theircareers.

Research Scholar Grants for Beginning Investigatorsare awarded to support basic, preclinical, clinical, or epidemiologic research projects initiated by inves-tigators in the first eight years of their independentresearch careers. Initial awards are made for up tofour years and up to $250,000 per year, including 25 percent indirect costs.

Postdoctoral Fellowships support the training ofresearchers who have just received their doctorate.Awards are made for one to three years, with progres-sive stipends of $28,000, $30,000, and $32,000 peryear, plus a $2,000 per year institutional allowance.

Clinical Research Training Grants for Junior Facultysupport the training of junior faculty within the firstfour years of independent faculty appointment toconduct mentored clinical, epidemiological, or healthpolicy and outcomes research. Awards are made for up to three years for up to $150,000 per year,including 25 percent indirect costs.

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The Future ofClinical ResearchTraining

In his keynote speech, Richard Lifton, Howard Hughes Medical Institute Inves-

tigator and Director of the Program in Cardiovascular Genetics at the Boyer

Center for Molecular Medicine at Yale University, commented that we have moved

beyond relying on the “handshake test” to define clinical research. “No longer

does clinical research require that an investigator and patient be in the same

room,” he added. With the advent of molecular biology, extensive research now

can be done on the pathogenesis and pathophysiology of human disease by

working at the DNA level on stored samples.

This advance gives researchers the ability to identify the underlying causes of

disease based entirely on the genetic nature of the disorder, without prior knowl-

edge of its pathophysiology. Thus, the paradigm that has emerged of positional

cloning of disease genes has revolutionized our understanding of human disease,

affecting every medical discipline, stressed Lifton. He added that as of February 15

of this year, 990 diseases with an inherited component had been characterized

at the molecular level, most within the past five years.

Although the majority of these are single-gene disorders, the genetic under-

standing of these disorders is central to discerning the fundamental physiologic

pathways that may be relevant to more common forms of disease. In addition, gene

targets in rare diseases may provide opportunities for therapeutic intervention for

common disorders. Lifton cited the example of the groundbreaking research on

familial hypercholesterolemia, conducted by Michael Brown and Joe Goldstein.

Although hypercholesterolemia is a rare disease, the work of Brown and Goldstein

led to the eventual development of HMG CoA reductase inhibitors, which have

had a profound effect on reducing risk of coronary artery disease in the general

population.

The challenge for clinical research is thatmost common diseases are complex, multi-etiologic disorders in which a multiplicity ofgenes interact with each other and with envi-ronmental factors, revealing subtle variationsin DNA. Common genetic variations areattracting enormous interest because it is suspected that they may contain clues toinborn susceptibility to common diseases.Clinical research must find the resources andintellectual capital to locate large enoughcohorts of patients with good enough pheno-types to relate common variants in the popu-lation. The goal is to determine how manygenes are imparting an effect in any given disease and to evaluate the magnitude of the effect.

To illustrate, Lifton described recentresearch on Alzheimer’s disease, which wasonce thought to be multifactorial and complex,but which is now emerging as a nearly mono-genetic disease. The inheritance at a singlelocus of a particular allele of an apolipoproteincontributes about 50 percent of the risk ofdevelopment of Alzheimer’s disease. Thus, asingle gene has a relatively large effect.

In addition to genomics, other companiontechnologies will advance the goals of clinicalresearch, such as the use of chips to monitorexpression of genes. This tool has the poten-tial to identify pathways that are altered in disease physiology, and they can be used as diagnostic tests (molecular diagnostics).Eventually, this technology will allow clinicalscientists to tailor treatment to underlyingabnormalities. In addition, functional MRI andNMR spectroscopy provide new tools to investigate fundamental physiology in livingpatients, such as the study of glucose trans-port in patients with diabetes. The study of invivo biochemistry in humans can only be conducted with the participation of clinical scientists, particularly the physician-scientist,emphasized Lifton.

“With the advent of the Human GenomeProject we are going from an open-ended

problem to a closed biological problem,” saidLifton. “This will have profound effects on theunderstanding of clinical medicine. In a shortperiod of time we will know all of the commongenetic variants. It will take the clinical scien-tist to figure out how to tie all the variants toparticular diseases.”

Lifton argued that after the genome ismapped, science will have to rely on clinicalinvestigation to conduct gene-based studies,to redefine the biology and the phenotypes ofdisease, and to refine diagnostic classifica-tions. He added that clinical research is bydefinition interdisciplinary and that clinicalinvestigators are comfortable with that para-digm and noted that unlike the basic scientist,the clinical scientist routinely seeks consulta-tion from other specialists to understand a clinical problem.

Yet, the funding trend has been away fromthe physician-scientist, a phenomenon thathas been repeatedly noted with dismay overthe past decade. Lifton’s view is optimistic,however, because he believes clinical

The Future of Clinical Research Training 19

The challenge for clinical research is that most common diseases are complex,multi-etiologic disordersin which a multiplicity of genes interact witheach other and with environmental factors,revealing subtle variations in DNA.

Richard LiftonYale University

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advances cannot come from the humangenome without the participation of the trainedclinician. The opportunities will draw the intel-lect, as long as the environment is conduciveto the physician trained in basic biology. Hereferred to a number of model programs, suchas the NIH MSTP, that have been essentialmechanisms for training physician-scientists.Still, Lifton said, economic forces, such asmedical school indebtedness and pressuresfrom academic health centers to increasepatient revenues, continue to dissuade physi-cians from a research career.

Who Should Conduct Clinical Research?Edward Holmes, Dean of the School of Medi-cine at Duke University, posed a schema forcategorizing those who conduct clinicalresearch. He believes that the training andresearch pathways of each type of investigatorare unique and that the various categoriesreflect the need for diverse mechanisms ofsupport.

■ Professional clinical investigator – spends80 percent of his or her time conductingclinical research (conducts Phase IIIclinical trials, outcomes research, epi-demiology); often has advanced trainingobtained beyond the M.D. (for example,M.S., M.P.H.).

■ Clinician investigator – primary effort is inpatient care, but may work with a profes-sional clinical investigator; has no spe-cial training in research; is the hands-onteam member in terms of patient contactand therefore is a critical player.

■ Physician-scientist – spends 80 percentof his or her time conducting research,typically laboratory investigation explor-ing the pathogenesis of human disease;works at the interface between the laboratory and the clinic (may conduct

Ethical Issues Facing BiomedicalResearchR. Alta Charo, Professor of Law and MedicalEthics at the University of Wisconsin, provided abroad view of emerging ethical issues in biomed-ical research. In addition to highlighting substan-tive topics that are the focus of debate—such asstem cell research, reproductive technology, genepatenting, and international research—Charonoted the special concerns that arise whenresearch is conducted with human subjects.

In the area of protecting human subjects inresearch, clinical science must contend with■ The great divide between research that is

regulated and research that is not, because ofsource of funding.

■ The challenge of distinguishing between experimental therapy and research.

■ The determination of what defines a humansubject in research and the assurance of privacy protection.

■ The technological imperative and the drive toproduce versus the assurance of patient safety.

■ The changing paradigm of research participation,with patients now demanding access to clinicaltrials.

The private sector can play an important role in■ Extending protections to all human subjects

in research, regardless of funding source.■ Developing and enforcing a code of ethics for

supported investigators.■ Ensuring the protection of vulnerable populations.■ Not supporting research that masquerades as

care.■ Supporting responsible multicultural initiatives

in research.

Phase I and II clinical trials); hasadvanced research training.

■ Ph.D. translational scientist – conductsclinically oriented research, such as outcomes research, health servicesresearch, biostatistics, epidemiology,animal models of human disease, andmolecular analysis; nearly always worksas a member of a team.

It is the physician-scientist group that ismost threatened in major medical centers,said Holmes, because of the time, effort, andexpense of training. The most effective point of entry for these individuals is the medical

student level, and students must be enticedearly so they can make their career choice atan appropriate time. Holmes would like to beable to offer 40 percent of his students theopportunity to take advanced training in sci-ence during the time they are receiving theirmedical education.

Holmes believes that the issue is not somuch whether Ph.D.s go to medical school orwhether medical students should get Ph.D.s,but rather that both groups must work togetherto be successful. “A medical school cannot be successful if it only has a single category of researcher,” he added, and “awards thatencourage people from basic and clinical

The Future of Clinical Research Training 21

Burroughs Wellcome Fund: Targeting Clinical and Interdisciplinary ResearchThe Burroughs Wellcome Fund supports several programs designed tofoster clinical and interdisciplinary research. Clinical Scientist Awardsin Translational Research are intended to foster the development, pro-ductivity, and mentoring capabilities of established physician-scientistswho will strengthen translational research—the two-way transfer ofinformation from the laboratory bench to clinical medicine.

Career Awards in the Biomedical Sciences are available to bothPh.D.s and M.D.s and provide support during the critical transitionfrom training to gaining research independence. Approximately 24awards are made annually. Each award provides research and salarysupport for two to three years of postdoctoral training and three yearsat the faculty level. The awards are transportable, and preliminary evaluation data indicate awardees have been highly successful in securing faculty positions.

Through its Interfaces in Science Program, the Fund supports theinterdisciplinary training of promising graduate and postdoctoral stu-dents from the physical, chemical, and computational sciences so theycan better apply their unique knowledge and talents to biological prob-lems. Awards are made to institutions that promote interdisciplinarytraining. Degree-granting institutions in the United States and Canadaare invited to propose graduate or postdoctoral training programs, or acombination of both.

22

science to work together are the most efficientmeans to meet that goal.” Holmes believes thisapproach should be especially attractive toprivate philanthropy, because of its interest intranslational research, which cannot be doneby a single individual or through a singleapproach.

Models of Training:Building Bridges Between theBasic and Clinical SciencesIrwin Arias, Chairman and Professor in theDepartment of Physiology and Professor ofMedicine at the Tufts University School ofMedicine, provided another view of filling thegap between basic and clinical research. “Anygap you want to cross necessitates a bridge,”he said. “There are many components to abridge, and we should look at all of them tosee how they come together to facilitate theoverall structure.” Quoting German pathologistWerner Kollath, Arias said, “Much is known,but unfortunately in different heads.”

Arias described the Pathobiology Programat Tufts University, of which he is the director.For the past 13 years, the Program has beenconducted for Ph.D. students, fellows, andfaculty, based on the following principles:

■ Because they are interested in a careerthat bridges basic science with humanhealth, virtually all graduate studentsselect a basic science department in amedical school rather than in a university.

■ The progressive depletion in physician-scientists has created an increasingnumber of excellent academic opportu-nities for Ph.D. scientists to be “first–class citizens” in outstanding clinicaldepartments where they work “with”rather than “for” physicians.

■ Bridging the gap between advances inbiology and disease is the greatest chal-lenge facing academic medicine today.Training basic scientists in pathophysi-

ology is only one mechanism for bridgingthis gap and does not replace efforts to increase the number of well-trainedphysician-scientists and M.D.-Ph.D.graduates.

The Program involves a one-semestercourse for 15 students that meets twice weeklyfor 90 minutes. The clinical-pathologic andbasic mechanisms of the 20 major diseases ofman are considered. During the course, stu-dents see patients, handle pathology speci-mens, and become informed about everymajor diagnostic and therapeutic facility in amodern hospital.

From the results of an outcome survey com-pleted by 182 students and fellows who havetaken the pathobiology course, 78 have com-pleted postdoctoral fellowships. Of these, allbut 2 have a position in industry or academia,and 33 have positions in biotechnical andpharmaceutical companies, where they areengaged in research that affects humanhealth. Twenty-seven have tenure track posi-tions in basic science departments in excel-lent institutions, and most have obtained grantsupport. It is of considerable interest that theremaining 22 individuals hold tenure trackpositions in six clinical departments in differentmedical schools throughout the country.

In addition to student and fellow outcomeresults, various other evidence reveals the Program’s success. For example, substantialinterest has been expressed by more than 50 institutions to replicate the Program. TheLucille P. Markey Charitable Trust supportednine such centers in 1997. A number of foun-dations, NIH, and the National Academy of

“Much is known, butunfortunately in different heads.”

Werner Kollath

Sciences have developed an interest in furtherevaluating the theory that Ph.D. students andfellows have an important role in bridgingadvancements in basic sciences with medicine.

Arias believes that it is important to “demys-tify medicine,” saying that “it is far easier toteach basic pathophysiology to bright Ph.D.students than to take last year’s chief medicalresidents and turn them into bench scientists.”

Graduate Training in Clinical InvestigationN. Franklin Adkinson, Jr., Physician-in-Chargeat the Johns Hopkins University Asthma andAllergy Clinics, described a graduate trainingprogram in clinical investigation, which servesas one model of clinical research training. Thefirst of its kind in the United States, the pro-gram was created in 1992 to address thegrowing national concern over the shortage ofacademic clinical investigators by trainingclinical fellows to be more effective clinical scientists.

Participants in the program acquire thenecessary skills to design and conduct clinicalinvestigations into emerging medical treat-ments and technologies, new diagnostic tech-niques, and new approaches to the study ofpathophysiology.

The usual career track is a four-year pro-gram, which leads to both clinical board eligi-bility in a medical discipline and a Ph.D. inclinical investigation. One full year of didactic

instruction is ordinarily taken after an initialclinical year in a medical or surgical specialty,providing the scientific grounding for subse-quent original research. Faculty from the pro-gram and a preceptor from the fellow’s homedivision or department jointly mentor thisresearch effort.

Fellows already enrolled in a clinical fellow-ship program at Johns Hopkins may apply toenter the program during their last year of clin-ical training. Program fellows normally receivetuition and stipend support consistent with theusual level of postdoctoral support for theirclinical specialties.

Funding for students usually comes from avariety of sources. Stipends and tuition can be provided from some NIH training grants or from other external training funds. Somedepartments have used internal funds to sup-port students or have obtained special fellow-ships from pharmaceutical companies, saidAdkinson. Many career development awardsare suitable sources of support, but they maybe difficult to obtain before completing the firstyear of the program. Adkinson reported thatone of the program’s greatest challenges hasbeen gathering sufficient financial support for what is essentially an interdisciplinary program. In addition, many students cannotcontinue with the program because of thepressures of indebtedness. Adkinson believesthat there is a vital role for public-private part-nerships in addressing this very real concern.

The Future of Clinical Research Training 23

Arias believes that it is important to “demystifymedicine,” saying that “it is far easier to teach

basic pathophysiology to bright Ph.D. students thanto take last year’s chief medical residents and turn

them into bench scientists.”

24

Wanted: Team BuildersIn addition to the knowledge base required offuture clinical investigators, J. Claude Bennett,President and Chief Operating Officer ofBioCryst Pharmaceuticals, said that post-genomic medicine will need team builders.Because molecular biology and clinical medicine are converging, said Bennett, drugdevelopers are desperately seeking highlytrained individuals who are conversant inbench and bedside science. This is a bigchallenge, he acknowledged, because therequirements in basic science and clinicaltraining are greater than ever before.

“Being in the pharmaceutical industry, I see the real need for clinical scientists,”

said Bennett. “But we can’t just wait for it tohappen. We have to be proactive. Formal programs are a necessity.”

Bennett mentioned that the pharmaceu-tical industry spends $20 billion to $25 billion annually on research, of which 10 to 12 per-cent is for basic discovery. Yet, all the drugscurrently on the market are probably related to500 molecular targets. With the Human GenomeProject, there may be 10,000 good targets fordrug development. “We need to efficiently andquickly explore the therapeutic opportunitiesprovided by those data,” he added.

Clinical scientists must have the necessaryknowledge base to use modern-day tools,such as understanding molecular concepts,how to use databases, and pharmacokinetics.

American Heart Association:A Track Record of Supporting Promising New ScientistsWithout sufficient funding during their early training, many talented young peoplemay be unable to pursue careers in academic medicine or the biological sciences.Helping to develop promising young scientists is a priority of the American HeartAssociation, which offers, through many of its affiliates, postdoctoral fellowships toprovide beginning researchers with essential research experience under the guidanceof a mentor. Other affiliate and national programs targeted at scientists in their firstfaculty positions facilitate the move from a mentor’s research program to a fullyindependent research effort.

Association Affiliate Research Programs are critical to new investigators. Most affiliates offer programs aimed at investigators who need postdoctoral training or initial project support before they can successfully compete for national awards, andaffiliate research committees—because of their familiarity with local universities,medical schools and hospitals—have a unique opportunity to cultivate the researchpotential of less experienced scientists.

National research programs focus on bridging the time between the postdoctoralfellowship and the time when a beginning investigator is prepared to independentlycompete for federal research funds. Scientist development awards and assistance for newly established investigators provide assistance to individuals beginning withtheir first faculty position and continuing through the next 9 to 13 years, while alsosupporting important research projects.

“Medical students are not being taught theseskills,” said Bennett. “There have to be mech-anisms to provide these proficiencies to indi-viduals who have a knowledge of humanbiology.”

Efforts of Private Funders toSupport the Development ofClinical InvestigatorsPrivate philanthropies, particularly voluntaryhealth agencies with a disease focus, histori-cally have played a significant role in filling thegap between the rate of advance in researchand the translation of new knowledge into therapies for human disease. Importantly, theprivate sector can search for the right nicheand experiment with innovative approaches.Private funders can use their funds to en-courage beginning investigators to enter aresearch area critical to the agency’s missionor encourage midcareer investigators tochange course in their direction.

For example, the Leukemia & LymphomaSociety provides support for individuals pur-suing careers in basic, clinical, or translationalresearch in leukemia, lymphoma, Hodgkin'sdisease, and myeloma. Likewise, the CancerResearch Fund of the Damon Runyon-WalterWinchell Foundation is a nonprofit organiza-tion dedicated to advancing cancer research.Sometimes the bequest of a foundation’sfounder requires that the organization spendits money in a particular area of research. TheDoris Duke Charitable Foundation is one suchorganization.

Foundations can target areas that are tradi-tionally underfunded. The Robert Wood John-son Foundation, for example, has supporteddevelopment of clinical investigators for 28 years, but has “built the fields that we feelhave been neglected that could improve thehealth of the population,” said Lewis Sandy,the Foundation’s Executive Vice President.

Organizations have used a variety ofapproaches to support training and havedeveloped new models in recent years asneeds have changed, including postdoctoralsupport, early career awards, and midcareerawards. Most are focused on the physicianseeking a career in clinical research.

Postdoctoral support is a common mecha-nism employed by many organizations. It istypically seen as a traditional approach to providing stable support for beginning inves-tigators to establish their laboratories.

This type of support has been a focus of theDamon Runyon-Walter Winchell Foundationsince 1946, reported Sarah Caddick, Directorof Award Programs for the Foundation’s Cancer Research Fund. It encourages thenation’s most promising young investigators topursue careers in cancer research by fundinginitial postdoctoral fellowships and DamonRunyon Scholar Awards. The Damon RunyonScholar Award was established to support thedevelopment of outstanding biomedical andbiochemical scientists as independent inves-tigators in the cancer field by ensuring the continuity of their research productivity at thecritical transition from research training to firstfaculty position.

Similarly, the Leukemia & Lymphoma Societyawards fellowships to promising investigatorswith less than two years of postdoctoralresearch training at the time of review. Fellowsare encouraged to embark on an academiccareer involving clinical or fundamental re-search in or related to leukemia, lymphoma,Hodgkin’s disease, and myeloma. Fellowshipsare $33,250 per year for three years.

The Future of Clinical Research Training 25

Importantly, the private sector can search for the right niche

and experiment with innovativeapproaches.

26

Private philanthropy also provides supportfor physicians who want to be trained inresearch. Since 1972, the Robert Wood John-son Foundation’s Clinical Scholars Programhas provided a two-year fellowship for phy-sicians interested in broad nonbiologicalaspects of health and health care, such as epidemiology, health economics, ethics, andhealth services research. Fellowships areavailable at seven sites around the country

that also receive support for institutional infra-structure and administration.

Elaine Gallin, Program Director for MedicalResearch at the Doris Duke Charitable Foun-dation, provided an example of midcareerawards for clinical investigators. The DorisDuke Distinguished Scientist Award targetsphysician-scientists who are midcareer level(associate level or full professor for no more than five years). The Award provides

Doris Duke Charitable Foundation:Targeting Clinical Training in Specific Disease Areas

The Clinical Scientist Award Program of the Doris Duke Charitable Foundation supports new investigators at the Assistant Professor level as they begin their careersas independent clinical researchers. The program is limited to the development ofresearchers in the areas of heart disease, AIDS, cancer, and sickle-cell anemia andother blood disorders.

The Foundation, which was formed in 1996, is specifically interested in ■ Studies on the etiology and pathogenesis of these diseases in man. ■ Therapeutic interventions. ■ Clinical trials. ■ Disease control research that investigates how scientifically obtained information

on prevention, early detection, and early diagnosis can be efficiently applied. ■ Epidemiological studies.■ Health outcomes research that either attempts to systematically determine the

risk/benefits and costs of various medical practices or attempts to utilize theseresults in defining more effective medical practice guidelines.

Candidates must have received an M.D. or equivalent degree from an accreditedinstitution within the past 10 years, must have completed 2 or more years of clinicaltraining and 2 years of postdoctoral experience, and must hold a full-time universityfaculty appointment.

Each three- to five-year award is for $100,000 per year. Should the applicantrequire additional training in order to meet the Foundation’s educational demands,an additional $25,000 will be awarded for six months of formal course work in theareas of bioethics, protection of human subjects, informed consent, study design,clinical trial record-keeping, quality assurance and control, and biostatistics.

stable research funding for investigators con-ducting translational research—five years at$600,000 per year.

Relieving Medical School Debt“One in four medical school graduates hasover $100,000 in debt after completing his or her degree,” said Caddick of the DamonRunyon-Walter Winchell Foundation. “In thisage of endless opportunity,” she remarked,“the Cancer Research Fund is delighted toannounce a new program to help rescue anendangered species—physicians willing todevote their careers to the development andapplication of new diagnostic approaches andtherapeutic strategies for cancer and cancerprevention through clinical investigation.” TheFund’s Clinical Investigator Award is ear-marked for young physicians willing to committhemselves to substantive and innovative clinical research; the Award bridges the gapbetween the research laboratory and patientcare.

The Cancer Research Fund created theprogram because of its belief that althoughthere has never been a more promising timefor clinical cancer research, fewer youngphysicians are entering this area of investiga-tion every year. Often, a major deterrent tophysicians making a commitment to clinicalinvestigation is their need to address majordebts that they acquired during medicaltraining.

The Fund’s new Award offers solutions tothis reality. The awardee and his or her seniormentor receive financial support for up to fiveyears, as well as assistance for certainresearch costs, such as the purchase ofequipment. Upon successful completion ofthe Clinical Investigator Award program, theFund will also retire up to $100,000 of anymedical school debt still owed by theawardee.

Applicants may apply during the final yearof their subspecialty training or within the first

two years of their junior faculty appointment.Each applicant must be nominated by his orher mentor and institution, and the institution is expected to guarantee the allocation of suf-ficient research and office space to ensure theproper start-up of the awardee. In addition, theinstitution must provide the difference in salarybetween the amount allocated by the Awardand the level appropriate for the position theapplicant holds at that institution.

The applicant is required to apply in con-junction with a mentor who is established inthe field of clinical translational cancerresearch or cancer prevention and epidemiol-ogy and who can provide the critical guidanceneeded during the Award period. The mentorwill receive partial salary support to be usedspecifically to foster the education of theawardee. A letter of commitment from the in-stitution is required defining the position thatthe applicant will occupy and outlining how the institution will enable the mentor to commita sufficient amount of time to the applicant’straining and development.

Caddick estimates that the cost to the Fundof a single award package is $1,125,000. Shereported that her phone has “been ringing offthe hook since the program was announced inNovember 1999.”

An Alternative to the CareerLadder ApproachRay Vento, Assistant Vice President for Scien-tific Program Administration, American LungAssociation, noted that his association, whichis the oldest voluntary health agency in thecountry, must constantly compete with othersimilar groups for support. The American Lung Association is a fundraising organizationrather than an endowed organization, and assuch it must balance national goals with localprograms. In addition, it spends most of itsfunds every year. Supporting the academicenterprise is not a primary goal.

The Future of Clinical Research Training 27

28

The Association has supported investigator-initiated research since 1915. In 1980, itswitched to the “career ladder approach,”said Vento, a strategy that was aimed at bring-ing young people into pulmonary medicineand allowing them to establish their independ-ence. Other modifications were made in theprogram in the ensuing years, changing someof the “steps” of the ladder and placing it in“different places,” added Vento. For example,doctoral awards were granted, and efforts weremade to reach out to minority communities.

In the 1990s, it became clear that to raisefunds as well as to support research, the Asso-ciation would have to change its strategy. In1991, the Association Council voted to focuson asthma, an approach that was important for advancing research but also for raising revenue. Since then, the Association has supported Asthma Research Centers thatcombine research and training.

Public Sector ProgramsHow to revitalize the nation’s clinical researchenterprise has been a popular topic in recentyears. Since 1996, NIH has focused efforts on how to stem the precipitous decline in thenumbers of physician-scientists. NIH becamealarmed when between 1994 and 1997 thenumber of first-time M.D. applicants plum-meted 31 percent, from 838 to 575 appli-cants. With only a 22 percent success rate in1997 among M.D. applicants, only 126 M.D.sserved as first-time principal investigators on NIH research project grants. NIH statisticsshowed a similar situation among M.D. post-doctoral trainees supported by NIH throughindividual fellowships and training grants. Thetotal number of M.D. postdoctoral traineesplateaued at around 2,300 in the 1980s. Butbetween 1992 and 1997, that pool shrank to1,261 such trainees.

In recent years, NIH has followed up on recommendations of the “Nathan Report”through such efforts as establishing the K23

and K24 training awards for young andmidlevel career faculty and expanding thenumber of medical students invited to take a year off from school to do research at NIH, reported Wendy Baldwin, NIH’s DeputyDirector for Extramural Research.

The purpose of the Mentored Patient-Oriented Research Career DevelopmentAward (K23) is to support the career develop-ment of investigators who have made a com-mitment to focus their research endeavors onpatient-oriented research, said Baldwin. Thismechanism provides support for three to fiveyears of supervised study and research forclinically trained professionals who have thepotential to develop into productive clinicalinvestigators focusing on patient-orientedresearch. In 1999, 139 awards were made.With a view towards stabilizing clinical re-search settings and preventing an interruptionin trainee mentoring, NIH has chosen to es-tablish the Midcareer Investigator Award inPatient-Oriented Research (K24). This awardis intended to relieve clinical investigators frompatient care duties and administrative respon-sibilities in order to increase the opportunitiesfor midcareer clinicians to become wellgrounded in patient-oriented research. In1999, 81 such awards were made, reportedBaldwin.

Baldwin said that NIH supports loan repay-ment programs in its intramural and extramuralprograms and would like to increase theamount of repayment awarded, a change thatwould require new congressional legislation.

Development and Supportof Clinical Training on theNIH CampusNIH also has undertaken new clinical trainingprograms in its own clinical setting, reportedJohn Gallin, Director of the NIH Warren GrantMagnuson Clinical Center. “Adequate trainingand the infrastructure to support principal

investigators conducting clinical research areessential to patient safety, protocol implemen-tation, and quality assurance,” said Gallin,“especially in interventional clinical trials.”Indeed, even in natural history studies, suchinfrastructure can only enhance the quality ofand access to the research by ensuring thatdata are collected as required by the protocoland are stored in a way that allows access tothe information without depending on any individual clinical researcher.

Training and education are first-orderrequirements to ensure that clinical trial inves-tigators have a consistent and completeunderstanding of their responsibilities, addedGallin. Clinical protocol design requires aworking knowledge of clinical trials method-ology, biostatistics, and regulatory medicine.Similarly, monitoring the trial during its execu-tion involves many distinct responsibilities,including reviewing each study subject’srecord to confirm his or her protocol eligibility,reviewing each study subject’s record todetermine compliance with the protocol,reporting adverse events to the InstitutionalReview Board (IRB), determining necessarychanges in the protocol and the informed consent documents and submitting them asprotocol amendments to the IRB, monitoringaccrual to the study, and stopping the studywhen the requirements of the study designhave been fulfilled or when it is clear that therate of accrual fails to meet expectations.

Under Gallin’s direction, all clinical principalinvestigators on the NIH campus are requiredto take an overview training course, or theequivalent, on the roles and responsibilities ofclinical investigators.

In recent years, this approach has beenextended beyond the NIH campus andbeyond the M.D. The NIH-Duke Training Pro-gram in Clinical Research leads to a Master of Health Sciences in Clinical Research, a professional degree awarded by the DukeUniversity School of Medicine. There is also anondegree option for qualified students whowant to pursue specific areas of interest. The

The Future of Clinical Research Training 29

Warren Grant Magnuson ClinicalCenter, National Institutes ofHealth: Introduction to the Principles and Practice of Clinical Research

Introduction to the Principles and Practice of Clinical Research is a studycurriculum on how to effectively conductclinical research that was established at the Warren G. Magnuson Clinical Center—the clinical research hospital of NIH. This curriculum is designed toteach researchers how to design a clinical trial. It covers epidemiologicmethods and focuses on study design and development, protocol preparation,patient monitoring, quality assurance,and regulatory issues and also includesdata management and legal and ethicalissues, including protection of humansubjects.

Course objectives are to become familiar with the basic epidemiologicmethods involved in clinical research; to be able to discuss the principlesinvolved in the ethics of clinicalresearch, the legal issues involved inclinical research, and the regulationsinvolved in human subjects research,including the role of IRBs in clinicalresearch; to become familiar with theprinciples and issues involved in moni-toring patient-oriented research; and to be able to discuss the infrastructurerequired in performing clinical researchand to understand the steps involved indeveloping and funding research studies.

30

Duke program, established in 1986, is one ofthe nation’s first training programs in clinicalresearch. This collaboration between the NIHWarren G. Magnuson Clinical Center and theDuke University School of Medicine marks thefirst time that the program has been madeavailable for long-distance learners, saidGallin. In addition, students at NIH can attendclasses at Duke by way of video conferencing.The curriculum covers the principles of clinicalresearch, including research design, statisticalanalysis, health economics, research ethics,and research management. The availability ofteleconferencing and telemedicine providesunprecedented opportunities for reaching outto clinical centers that have been “islands,”said Gallin.

Finally, Gallin mentioned a program offeredto medical students between their third andfourth year of training. Like the HowardHughes Medical Institute-NIH Cloister Program,students spend a year working with a researchmentor on campus to gain exposure to labo-ratory investigation. The program is funded by Pfizer, Inc., which committed $1.6 millionover two years to the National Foundation forBiomedical Research to sponsor 16 clinicalresearch training fellows at NIH.

The program focuses on third-year medicaland dental students and brings them to theNIH campus for a year of didactic and practi-cal hands-on experience. The students areselected in a competitive process by an advi-sory committee of experts in clinical research.Students work in NIH laboratories and clinicsand are mentored by senior clinical investiga-tors. They also take a core course in clinicalresearch and receive a stipend for livingexpenses and other support.

The Medical Scientist Training ProgramThe NIH MSTP, administered by Bert Shapiro, supports the integrated medical and gradu-ate research training that is required for the

investigation of human diseases. It is widelybelieved to be a model that works, as 85 per-cent of the individuals who participate in theProgram remain actively involved in academicmedicine.

The MSTP assures highly selected traineesa choice of a wide range of pertinent graduateprograms in the biological, chemical, andphysical sciences, which, when combinedwith training in medicine, lead to the M.D.-Ph.D. degree. Programs are encouraged toprovide a breadth of doctoral research trainingopportunities consistent with individual institu-tional strengths. In addition to the above dis-ciplines, support of trainees in other disci-plines, such as computer sciences, social andbehavioral sciences, economics, epidemiol-ogy, public health, bioengineering, biostatis-tics, and bioethics, is appropriate. Accordingto Shapiro, MSTP programs should be flexibleand adaptable in providing each trainee withthe appropriate background in the sciencesrelevant to medicine, yet they should be suffi-ciently rigorous to enable graduates to func-tion independently in both basic research andclinical investigation. In 1999, the Programawarded $26 million to 40 participating insti-tutions. This type of program provides “the perfect model” for collaboration between thepublic sector and the private sector, com-mented Shapiro, who added that despite thesuccess of the Program, the participating insti-tutions are chronically underfunded. Clinicalresearch training is expensive, he concluded,and public-private sector partnerships areessential in bridging the gap.

Goals for Private FundersThere are many new and exciting opportunitiesin clinical research that have been provided bythe genetic revolution and other scientificadvances. “We are seeing increasing demandfor clinical research as we enter into this much-heralded postgenomic era,” concludedRichard Lifton. “But we have to overcomeenormous institutional challenges as the

traditional streams of revenue are redirected or dry up.” Two major investment areas haveemerged to advance clinical research—human capital and training programs. Bothrequire innovative approaches as we enterthe realm of molecular medicine.

Human Capital

1. The development of clinical scientists isa good target for private support. How-ever, as with training basic scientists, it is critically important to support youngclinical scientists, although other steps in the ladder also require attention.Research experiences during medicalschool, such as the Howard HughesMedical Institute-NIH Cloister Programand the NIH-Pfizer Clinical ResearchTraining Program, are excellent exam-ples of programs that support clinicalinvestigators early in their careers,before receiving the doctorate.

2. The M.D.-Ph.D. is the most successfulmodel for the development of clinical scientists. This model should be sup-ported by the private sector in order toexpand the current numbers of traineesat currently funded sites or to developnew programs at institutions that couldthen become eligible for NIH support.The NIH program currently supports onlysix years of training, leaving institutionsto fill the gap for what is an eight-yearprogram.

3. Despite the predominance of the M.D.-Ph.D. scientist, there are other essentialtypes of physician-scientists, and thesescientists require different types of support.

• Numerous new master’s-level pro-grams are in development for clinicalresearch training. The private sectorcan make a contribution by assistingwith tuition support.

• Ph.D.s, if trained in pathobiology orother human disease constructs, canprovide an invaluable resource to theclinical research team.

4. Transition support to assist individuals atkey points in their training and careerdevelopment, such as between thesiswork and the first independent facultyposition, can be essential to preventyoung scientists from leaving research.In this respect, debt relief is crucial.Because it is difficult for governmentagencies to provide adequate funds inthis area, private philanthropy can makea valuable contribution.

Training Programs

1. The development of multidisciplinaryand generic training programs in clinicalresearch is urgently needed, and thecollaboration of disease-oriented groupsto provide such support could make acritical difference. Such a consortiumcould provide funds for junior faculty andgraduate students as they make impor-tant education and career transitions.

2. There are a number of possible modelsfor Ph.D. training for clinical researchthat could be targets of private support.

3. The private sector could support inno-vative mechanisms by which to developand support mentorship skills in new andexisting faculty.

4. Although a number of master’s-level programs for clinical research have been funded, innovation in trainingapproaches is needed to meet emergingneeds in academic and industrial science.

The Future of Clinical Research Training 31

American Association for the Advancement of ScienceGrantsNet and NextWaveEllis Rubinstein, Editor of Science magazine, traced the progress of theAmerican Association for the Advancement of Science Websites, GrantsNet(www.grantsnet.org) and NextWave (www.nextwave.org) (developedthrough collaborations with the Howard Hughes Medical Institute and the Burroughs Wellcome Fund), both of which represent unusual partner-ships for a science magazine that has been produced as a sole venture for most of its 120 years. GrantsNet, part of the Association’s NextWave Website, is a free, searchable online database of funding options for biomedical scientists in the training phases of their careers. The site wasfunded by a three-year, $900,000 grant from the Howard Hughes MedicalInstitute and has been in operation for two years. Currently, it has 250 par-ticipating organizations, 52,000 registered users, and 604 programs in its database.

NextWave, established through support from the Burroughs WellcomeFund, is the parent of GrantsNet. In operation since 1995, NextWave targetsgraduate and postdoctoral students and provides career advice and theopportunity for online exchanges among young scientists and betweenyoung scientists and experts. The site currently features a career develop-ment center that was initiated through a grant from the Burroughs WellcomeFund and the Howard Hughes Medical Institute, and, in addition to supportthrough a number of professional societies and government agencies,NextWave has a number of international collaborators.

Current plans include the redesign of the GrantsNet homepage, thedevelopment of a database for undergraduates in search of research opportunities, and expanded international scientific collaborations. BothGrantsNet and NextWave, said Mr. Rubinstein, demonstrate what can beaccomplished by combining Web-based technologies for electronic grants-making with effective partnerships with organizations that have been at theforefront of the use of these technologies.

Howard Hughes Medical InstituteGraduate Competition SystemJoseph Perpich, Vice President for Grants and Special Programs, focusedon the online application system the Institute has developed for its graduatefellowship programs—the Graduate Competition System. Prospective appli-cants access the system by going to the graduate program’s home page,where they are linked to program announcements, eligibility criteria, appli-cation forms, and instructions and tips. An applicant registers and is given a personal identification number (PIN) and password for the application, as well as PINs and passwords for third parties, such as mentors and references, who also use the Web system to submit information.

Several features of the system are particularly useful. An applicationchecklist, for example, tells applicants which third-party materials—transcripts, references, mentor materials—have been received by the Insti-tute. This relieves staff from having to field many telephone calls and e-mailsfrom applicants. Data entry is handled in two ways: Some fields use free-form entry (for example, current position), while others are selected from

Appendix A:

The New

World of

Electronic

Grantsmaking

32

standardized lists (for example, institutional affiliation,research field). Essay material on the application ishandled by uploading a Rich Text Format file.

Applicants and mentors must complete the formsonline and submit them to the Institute via the Web.After the application is submitted, the data are trans-ferred to the non-Web component of the GraduateCompetition System for management during the reviewand award process. For most Institute grants pro-grams, the review process is handled almost entirelyonline. The Graduate Competition System is viewed bythe Institute as "shareware" that can be made availableto other funders at no cost (although funders would haveto assume costs associated with any adaptations).

In addition, the Institute has undertaken significantstandardization efforts. As a result, staff can analyzeprograms in terms of an array of variables and can alsoconduct a variety of cross-program analyses (for exam-ple, educational origins of graduate fellows, number ofunder-represented minorities participating in Institute-supported programs).

American Cancer Society Foundation CommonsThe American Cancer Society has established theFoundation Commons Consortium, which provides ashared online application system for voluntary healthagencies (www.foundationcommons.org). The Societycoordinates this system, explained Dr. T.J. Koerner,Director of Research Information Management, with anumber of other voluntary health agencies, includingthe Alzheimer’s Association, the Cystic Fibrosis Foun-dation, and the Juvenile Diabetes Foundation. Science-Wise, the vendor that developed the system, isexperienced with e-commerce applications and grantprocesses and serves as the point of contact for themember organizations, each of which has differentneeds for data and services.

At this time, Foundation Commons is not sharinggrant results and is instead focusing on the applicationprocess. The system does not attempt to alter internalinstitutional review processes, but rather frees appli-cants from the burden of updating multiple profiles bycreating one common profile for each applicant. Afterselecting the consortium member to which they wish toapply, users register by filling out and submitting a per-sonal profile information form. They then download theapplication in Portable Document Format (PDF), com-plete the application offline, and submit the applicationin electronic and paper format per the consortium

member’s instructions. The information goes to theFoundation Commons’ central database and is trans-ferred electronically to the consortium member’s ownsystem. Because the technology allows the use of bothspecialized and standardized fields, data standardiza-tion is used where it makes sense. For example,through this system, an application can be submittedto any organization that uses the federal government194 Data Set standard.

To save completed forms in PDF, applicants arerequired to have access to Adobe Acrobat Exchange4.0, which, unlike Adobe Acrobat Reader, is not free,although this is the system’s only limiting technologicalrequirement. In discussion, participants noted the lackof inexpensive, nonproprietary software as a commonobstacle to use and standardization of online applica-tion systems and emphasized the need to think care-fully about how the proliferation and use of thesesystems may affect those who are submitting researchapplications, where overhead and indirect costs areinvolved.

National Science FoundationFastLane ProjectThe National Science Foundation developed this Web-based system for the submission and review ofgrant proposals (www.fastlane.nsf.gov) and currentlyreceives approximately 22,000 applications a yearthrough the site. In addition, approximately 80,000reviews and 99 percent of project reports have beenreceived through FastLane. Carolyn Miller, BranchChief, External Systems, stressed the importance ofhaving appropriate external and internal functions inplace in order for this kind of system to work. Externalfunctions that need to be in place at agencies includeproposal preparation and submission; referencepreparation and submission; proposal review; paneltravel; and organizational management. The Founda-tion provides a number of internal functions to its staffthrough FastLane, such as an electronic jacket thatincludes all available information; a review manage-ment utility that allows staff to manage reviewers andpanels; functions that provide the ability to generatereports and track progress; and the ability to transferinformation to and from internal processing systems.

From the perspective of proposal processing, animportant advantage to this system is that parts of thereview process can be initiated before the actualreview begins. Overall, Ms. Miller noted, processesthat involve mainly straightforward data transactions

Appendix A: The New World of Electronic Grantsmaking 33

have worked well; in the area of awards management,for example, the system has significantly reduced thetime it takes to apply and receive approval for a no-costextension. The most complicated process to imple-ment electronically has been proposal preparation.

FastLane’s vision for the future, one that will helpmeet the challenges of Internet accessibility and serverperformance (especially when deadlines are involved),is one of a connection-free process for all FastLanefunctions. Through a connection-free process, forexample, reviewers can download a function and workoff-line and then submit their work either through e-mailor the Web. Another important challenge is the need forsoftware that can be used with any word processor andthat can support scientific images. Currently, FastLaneuses PDF files for documents that include scientificillustrations; however, a promising competitor, calledGoScript 6.0, is now available and is supported onUnix, PC, and Mac platforms.

National Institutes of HealthNIH Electronic Research Administration Commons Project (NIH Commons)George Stone, Chief, Commons, Extramural Inven-tions, and Technology Resources Branch at theNational Institutes of Health (NIH), noted that the fed-eral government’s mandate to reduce the amount ofpaperwork within the next 18 months will significantlyaffect how the government processes applications andawards. Through its NIH Electronic Research Adminis-tration Commons (www-commons.cit.nih.gov), NIH isworking to accomplish this transition from paper toelectronic processes throughout the grants lifecycleand to make its systems more applicable and less pro-prietary in a thoughtful way, despite the speed withwhich the new technology is advancing and the challenges that are presented in replacing the 30- to 50-year-old legacy systems. The NIH Commons is implementing Internet processes for informationexchange through two main strategies: The first is todisseminate unrestricted information, which does notrequire a user log-in. The second is to provide for theexchange of confidential information, which requiresregistration and log-in.

NIH Commons uses a system of controlled deploy-ment in which the system is first offered to a small number of organizations that have expressed interestin it, and then, after the system is refined based onfeedback from these organizations, it is offered more

widely. Currently about 125 schools are using the sys-tem, which is now considered to be in expandeddeployment. "To be successful, we must take intoaccount the diversity of the grantee population andaccommodate the differences through a combinationof structure and flexibility," remarked Dr. Stone, whoadded that NIH Commons employs a common stan-dard, the 194 Data Set, which serves as a commondata dictionary that is used by both the governmentand the private sector.

NIH Commons supports an online electronic pro-filing system and provides a secure and confidentialenvironment within which users can conduct their business. Because the goal is to be flexible in the useof technological approaches, NIH Commons tries toavoid the use of proprietary software, such as PDF;however, no nonproprietary method currently is avail-able that can be used for the scientific illustrations thatare often included in applications. NIH Commons willsupport Extensible Markup Language technology,which, once a tool is available to support it, could render PDF obsolete. At this time, the system adheresto standard syntax formats, such as Interactive Web, Electronic Data Interchange, HyperText Markup Language, and Adobe forms filling.

Recent developments at NIH Commons include theuse of e-Snap for the submission of noncompetingapplication data into a streamlined awards processand the use of e-Fellowships for the preparation andsubmission of fellowship applications via InteractiveWeb. X-train, for electronic trainee activities, is a secureinteractive Website for statement of appointments andtermination notices of extramural trainees. NIH Com-mons also supports a profiling system and a system forchecking the status of pending applications. In addi-tion, an application viewer is available that allows anapplicant to see how the application will look beforesubmitting it.

Discussion focused on whether the Web couldmake it easier for those who are not serious applicantsto apply for awards and in the process disrupt grants-making sites. Dr. Stone noted that because NIH Com-mons uses a strong authorization protocol, such usewould be unlikely. Registration includes a faxed author-izing signature, and all information that is provided bythe applicant is validated. In addition, affiliation isrequired in order to submit an application, except forfellowship applications, which must be submitted by asponsor in order to be accepted.

34

Appendix B:

Meeting

Agenda

35

Monday, February 14, 2000

Welcome and Opening Remarks■ Thomas R. Cech, Ph.D., President, Howard Hughes Medical Institute■ Enriqueta Bond, Ph.D., Burroughs Wellcome Fund■ John Stevens, M.D., American Cancer Society

Forum on the New World of Electronic GrantsmakingModerator: Joseph G. Perpich, M.D., J.D., Howard Hughes Medical Institute■ Ellis Rubinstein, “GrantsNet,” “NextWave,” Science magazine■ T. J. Koerner, Ph.D., “Foundation Commons,” American Cancer Society■ Carolyn Miller, “FastLane,” National Science Foundation■ George Stone, Ph.D., “NIH Commons,” National Institutes of Health

Tuesday, February 15, 2000Basic Biomedical Research Training

WelcomeThomas R. Cech, Ph.D., President, Howard Hughes Medical Institute

Perspectives on the Future of Basic Biomedical ResearchDavid Botstein, Ph.D., Stanford University

Competencies Required of the Next Generation of Basic ScientistsThomas R. Cech, Ph.D., Howard Hughes Medical Institute

Challenges and Opportunities in Training Basic Biomedical ScientistsModerator: Thomas R. Cech, Ph.D., Howard Hughes Medical Institute■ Stephen Burley, M.D., D.Phil., Howard Hughes Medical Institute,

Rockefeller University■ Nicholas R. Cozzarelli, Ph.D., University of California-Berkeley■ Freeman A. Hrabowski, Ph.D., University of Maryland, Baltimore County■ David Botstein, Ph.D., Stanford University

Current Programs and Plans of Private FundersModerator: Donella Wilson, Ph.D., American Cancer Society■ Jaleh Daie, Ph.D., The David and Lucile Packard Foundation■ Susan Barnett, M.A., American Heart Association■ Robert Goldstein, M.D., Ph.D., Juvenile Diabetes Foundation■ Maria Pellegrini, Ph.D., W.M. Keck Foundation

Current Programs and Plans of Federal FundersModerator: Michael Teitelbaum, Ph.D., Alfred P. Sloan Foundation■ Marvin Cassman, Ph.D., National Institute of General Medical Sciences■ Mary Clutter, Ph.D., National Science Foundation■ Elke Jordan, Ph.D., National Human Genome Research Institute■ John Ruffin, Ph.D., National Institutes of Health

Summary of the DayDavid Botstein, Ph.D., Stanford University

Evening SpeakerEthical Issues Associated with Future Biomedical ResearchR. Alta Charo, J.D., University of Wisconsin-Madison

Wednesday, February 16, 2000Clinical Research Training

WelcomeEnriqueta Bond, Ph.D., President, Burroughs Wellcome Fund

The Future of Clinical ResearchRichard P. Lifton, M.D., Ph.D., Howard Hughes Medical Institute,

Yale University School of Medicine

Challenges and Opportunities in Training Clinical ResearchersModerator: John Stevens, M.D., American Cancer Society■ Edward Holmes, M.D., Duke University Medical Center■ Irwin M. Arias, M.D., Tufts University■ N. Franklin Adkinson, Jr., M.D., Johns Hopkins University■ J. Claude Bennett, M.D., BioCryst Pharmaceuticals

Current Programs and Plans of Private FundersModerator: Lewis G. Sandy, M.D., Robert Wood Johnson Foundation■ Elaine Gallin, Ph.D., Doris Duke Charitable Foundation■ Sarah Caddick, Ph.D., Damon Runyon-Walter Winchell Foundation ■ Marshall Lichtman, M.D., The Leukemia & Lymphoma Society■ Ray Vento, American Lung Association

Current Programs and Plans of Federal Funders of ResearchModerator: Myrl Weinberg, CAE, National Health Council■ John I. Gallin, M.D., Warren G. Magnuson Clinical Center ■ Bert Shapiro, Ph.D., National Institute of General Medical Sciences■ Wendy Baldwin, Ph.D., National Institutes of Health

Summary of the DayRichard P. Lifton, M.D., Ph.D., Howard Hughes Medical Institute,

Yale University School of Medicine

Closing Remarks and AdjournmentJohn Stevens, M.D., American Cancer SocietyEnriqueta Bond, Ph.D., Burroughs Wellcome FundThomas R. Cech, Ph.D., Howard Hughes Medical Institute

36

Appendix C:

Participants

37

Adkinson, N. Franklin, Jr. (M.D.)Professor of Medicine and

Program DirectorJohns Hopkins Graduate Training

Program in Clinical InvestigationJohns Hopkins School of Medicine5501 Hopkins Bayview CircleBaltimore, MD 21224-6801Tel: (410) 550-2051Fax: (410) 550-2055fadkinso@welch.jhu.edu

Agyapong, CarrSenior Program and

Communications OfficerBurroughs Wellcome Fund21 T.W. Alexander DriveP.O. Box 13901Research Triangle Park,

NC 27709Tel: (919) 991-5103Fax: (919) 991-5163www.bwfund.org

Alexander, JamesAlexander Associates2129 Central Park Ave.Evanston, IL 60201Tel: (847) 475-0034Fax: (847) 475-6780alexassocs@aol.com

Alexander, Linda (Ph.D.)American Social Health

AssociationP.O. Box 13827Research Triangle Park, NC 27709Tel: (919) 361-8400Fax: (919) 361-8425

Arias, Irwin M. (M.D.)Professor and Chairman,

Department of PhysiologyProfessor of MedicineTufts University School of

Medicine136 Harrison Ave.Boston, MA 02111Tel: (617) 636-6739Fax: (617) 636-0445iarias@infonet.tufts.edu

Bachman, RobertPresidentAmerican Foundation for

Pharmaceutical EducationOne Church Street, Suite 202Rockville, MD 20850Tel: (301) 738-2160Fax: (301) 738-2161afpe@wprldnet.att.net

Baldwin, Wendy (Ph.D.)Deputy Director for Extramural

ResearchNational Institutes of HealthBldg. 1, Room 1449000 Rockville PikeBethesda, MD 20892Tel: (301) 496-1096Fax: (301) 402-3469baldwinw@od1tm1.od.nih.gov

Barlin, Wayne A. (B.S., J.D.)Vice President and General

CounselThe Wallace H. Coulter

Foundation790 N.W. 107th Ave, Suite 215Miami, FL 33172Tel: (305) 559-2991Fax: (305) 559-5490waynebarlin@whcf.org

Barnett, Susan (M.A.)Vice President of Research

Administration American Heart Association7272 Greenville Ave.Dallas, TX 75231Tel: (214) 373-6300susanb@heart.org

Battle, Constance U. (M.D.)Executive DirectorFoundation for the National

Institutes of Health, Inc.1 Cloister Court, Suite 152Bethesda, MD 20814-1460Tel: (301) 402-5311Fax: (301) 480-2752cubattle@fnih.org

Bellermann, Peter (M.P.A.)PresidentNational Neurofibromatosis

Foundation (New York)Chairman, International

Neurofibromatosis Association(Luxemberg)

Member, American Society ofHuman Genetics

Member, New York Academy of Sciences

95 Pine Street, 16th floorNew York, NY 10005Tel: (212) 344-6633 ext.29Fax: (212) 747-0004pbellermann@nf.org

Bennett, J. Claude (M.D.)President and Chief Operating

OfficerBioCryst Pharmaceuticals, Inc.2190 Parkway Lake DriveBirmingham, AL 35244Tel: (205) 444-4600Fax: (205) 444-4640cbennett@biocryst.com

Blackwood, M. Anne (M.D.)Senior Scholar/Assistant ProfessorCenter for Clinical Epidemiology

and BiostatisticsUniversity of Pennsylvania School

of Medicine937 Blockley Hall423 Guardian Dr.Philadelphia, PA 19104-6021Tel: (215) 573-6261Fax: (215) 573-2265ablackwo@cceb.med.upenn.edu

Bond, Enriqueta C. (Ph.D.)PresidentBurroughs Wellcome Fund21 T.W. Alexander Dr.P.O. Box 13901Research Triangle Park,

NC 27709-3901 Tel: (919) 991-5100Fax: (919) 991-5160qbond@bwfund.org

Botstein, David (Ph.D.)Professor and ChairmanDepartment of Genetics, L329Stanford University School of

MedicineStanford, CA 94305-5120Tel: (650) 723-3488Fax: (650) 723-7016botstein@genome.stanford.edu

Boyd, Dana (M.S.)Executive DirectorThe Stanley J. Sarnoff Endow-

ment for Cardiovascular Science731 Walker Rd., Suite G2Great Falls, VA 22066Tel: (703) 759-7600Fax: (703) 759-7838dboyd@cais.com

Brown, Donald D. (M.D.)PresidentLife Sciences Research

Foundation115 W. University PkwyBaltimore, MD 21210Tel: (410) 467-2597Fax: (410) 243-6311brown@mail1.ciwemb.edu

Burley, Stephen L. (M.D., D. Phil., F.R.S.C.)ProfessorRockefeller University1230 York Ave., Box 55New York, NY 10021Tel: (212) 327-8336Fax: (212) 327-8337burley@rockvax.rockefeller.edu

Caddick, Sarah J. (Ph.D.)Director of Award ProgramsCancer Research Fund of the

Damon Runyon – WalterWinchell Foundation

675 Third Ave., 25th floorNew York, NY 10017Tel: (212) 697-9588Fax: (212) 697-4950sarah.caddick@cancerresearch-

fund.org

Carlson, Heather A. (Ph.D.)American Cancer Society

Postdoctoral FellowLa Jolla Interfaces in ScienceBurroughs Wellcome Postdoctoral

FellowDepartment of Chemistry and

BiochemistryDepartment of PharmacologyUniversity of California,

San Diego9500 Gilman Drive,

4202 Urey HallLa Jolla, CA 92093-0365Tel: (858) 822-1469Fax: (858) 534-7042hcarlson@mccammon.ucsd.edu

Cassman, Marvin (Ph.D.)DirectorNational Institute of General

Medical SciencesNatcher Building, Room 2An.1245 Center Drive, MSC 6200Bethesda, MD 20892-6200Tel: (301) 594-2172Fax: (301) 402-0156cassmanm@gm1.nigms.nih.gov

Cates, Joan R. (MPH)Vice President of Development

and PolicyAmerican Social Health

AssociationP.O. Box 13827Research Triangle Park, NC 27709Tel: (919) 361-8417Fax: (919) 361-8425joacat@ashastd.org

Cech, Thomas R. (Ph.D.)President Howard Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789

Charo, R. Alta (J.D.)Professor of Law and Medical

EthicsUniversity of Wisconsin Law and

Medical Schools7111 Law Building975 Bascom MallMadison, WI 53706Tel: (608) 262-5015Fax: (608) 262-5485racharo@facstaff.wisc.edu

38

Choppin, Purnell W. (M.D.)President EmeritusHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789

Clayton, David A. (Ph.D.)Vice President for Science

DevelopmentHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8553Fax: (301) 215-8558clayton@hhmi.org

Clutter, Mary E. (Ph.D.)Assistant DirectorNational Science Foundation4201 Wilson Boulevard, Room 605Arlington, VA 22230Tel: (703) 306-1400Fax: (703) 306-0343

Coffman, Thomas M.President/CEOOrthopaedic Research and

Education Foundation6300 N. River Road, Suite 700Rosemont, IL 60018Tel: (847) 698-9980Fax: (847) 698-7806coffman@oref.org

Cohen, RobertThe Marcus Foundation, Inc.2455 Paces Ferry Rd., Bldg. C,

22nd floorAtlanta, GA 30338-4024

Cox, CarolManager, Research ProgramsCrohn’s & Colitis Foundation of

America386 Park Ave. South, 17th floorNew York, NY 10016-8804Tel: (212) 685-3440 ext.218 or

(800) 932-2423Fax: (212) 778-4098ccox@ccfa.org

Cozzarelli, Nicholas R. (Ph.D.)ProfessorDepartment of Molecular and Cell

BiologyUniversity of California, Berkeley401 Barker Hall #3204Berkeley, CA 94720-3204Tel: (510) 642-5266Fax: (510) 643-1079ncozzare@socrates.berkeley.edu

Daie, Jaleh (Ph.D.)Director, Science ProgramThe David and Lucile Packard

Foundation300 Second St., Suite 200Los Altos, CA 94022Tel: (650) 917-7291Fax: (650) 941-7320

Dhodapkar, Madhav (M.D.)Clinical Scholar/Assistant

ProfessorLaboratory of Cellular Physiology

and ImmunologyRockefeller University1230 York AvenueNew York, NY 10021

Dorrance, JacquelineExecutive DirectorArnold and Mabel Beckman

Foundation100 Academy DriveIrvine, CA 92612Tel: (949) 721-2222Fax: (949) 721-2225jdorrance@beckman-

foundation.com

Dukes, AmyRockefeller Brothers Fund437 Madison Avenue, 37th floorNew York, NY 10022-7001Tel: (212) 812-4200Fax: (212) 812-4299rock@rbf.org

Dumelle, FranAmerican Lung Association1740 BroadwayNew York, NY 10019-4374Tel: (212) 315-8793

Eckardt, Robert (Dr.P.H.)Cleveland Foundation1422 Euclid Avenue, Suite 1400Cleveland, OH 44115Tel: (216) 861-3810Fax: (216) 861-1729

Fambrough, Douglas M. (Ph.D.)Professor of BiologyScientific Director, Searle

Scholars ProgramDepartment of BiologyJohns Hopkins University3400 N. Charles St.Baltimore, MD 21218Tel: (410) 516-5174Fax: (410) 516-6157fambro@jhu.edu or ssp@jhu.edu

Filner, Barbara (Ph.D.)Senior Program Officer for

Analysis and AssessmentOffice of Grants and Special

ProgramsHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8885Fax: (301) 215-8888filnerb@hhmi.org

Fitzpatrick, Susan M. (Ph.D.)Program DirectorJames S. McDonnell Foundation1034 South Brentwood,

Suite 1850St. Louis, MO 63117Tel: (314) 721-1532Fax: (314) 721-7421susan@jsmf.org

Flescher, Dianne C.Senior Director, Research and

Professional EducationEpilepsy Foundation4531 Garden City DriveLandover, MD 20785Tel: (301) 459-3700Fax: (301) 577-2684

Appendix C: Participants 39

Ford, Roxanne M. (B.S.)Program DirectorW.M. Keck Foundation555 South Flower St., Suite 3230Los Angeles, CA 90071Tel: (213) 612-2021Fax: (213) 614-0934rford@wmkeck.org

Foster, StephenS. A. Foster Associates299 W. 12th St., 6FNew York, NY 10014Tel: (212) 727-0775Fax: (212) 727-0775safoster@bellatlantic.net

Franko, Maryrose (Ph.D.)Senior Predoctoral Program

Analyst and GrantsNet ProjectManager

Howard Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8880Fax: (301) 215-8888frankom@hhmi.org

Gallin, Elaine K. (Ph.D.)Program Director for Medical

ResearchDoris Duke Charitable Foundation650 Fifth Ave., 19th floorNew York, NY 10019Tel: (212) 974-7104Fax: (212) 974-7590egallin@ddcf.org

Gallin, John I. (M.D.)Director, Warren G. Magnuson

Clinical CenterNational Institutes of HealthBldg. 10, Room C148Bethesda, MD 20892-1504Tel: (301) 496-4114Fax: (301) 402-0166jgallin@cc.nih.gov

Gold, StevenDavid B. Gold FoundationSustainable Grantmaking Partners4 Embarcadero #3610San Francisco, CA 94111Tel: (415) 288-9535Fax: (415) 288-9549sgold1280@aol.com

Goldstein, Robert A. (M.D., Ph.D.)Chief Scientific OfficerJuvenile Diabetes Foundation

International120 Wall Street, 19th floorNew York, NY 10005-4001Tel: (212) 785-9500Fax: (212) 785-9595rgoldstein@jdfcure.org

Goodman, David M. (Ph.D.)Director of Foundation RelationsFox Chase Cancer Center7701 Burholme Ave.Philadelphia, PA 19111Tel: (215) 728-3165 Fax: (215) 728-4799dm_goodman@fccc.edu

Gruman, Jessie C.Executive DirectorCenter for the Advancement of

Health2000 Florida Ave. N.W., Suite 210Washington, DC 20009Tel: (202) 387-2829Fax: (202) 387-2857jgruman@cfah.org

Hanna, Kathi E. (Ph.D.)Science and Health Policy

Consultant745 Barstow RoadPrince Frederick, MD 20678Tel: (301) 494-0900Fax. (410) 414-2618khanna@chesapeake.net

Hans, Sherrie L. (Ph.D.)Program Officer, Health and

Human ServicesThe Pew Charitable Trusts2005 Market St., Suite 1700Philadelphia, PA 19103Tel: (215) 575-4850Fax: (215) 575-4888shans@pewtrusts.com

Hirschhorn, Kurt (M.D.)Professor of Pedicatrics, Human

Genetics and MedicineMount Sinai School of Medicine –

Representing March of DimesOne Gustave L. Levy Place –

Box 1497New York, NY 10029-6574Tel: (212) 241-4305Fax: (212) 289-8569kurt.hirschhorn@mssm.edu

Holden, AlisonSenior Manager, Corporate and

Pharmaceutical RelationsCrohn’s and Colitis Foundation

of America386 Park Avenue South,

17th floorNew York, NY 10016Tel: (212) 685-3440 ext.247Fax: (212) 779-4098aholden@ccfa.org

Holmes, Edward (M.D.)Dean, School of MedicineDuke University Medical CenterBox 3701Durham, NC 27710Tel: (919) 684-2455Fax: (919) 684-0208holme023@mc.duke.edu

Horn, Mark (M.D.)Pfizer, Inc.235 East 42nd StreetNew York, NY 10017-5755Tel: (212) 573-1307Fax: (212) 573-2965

Houston, Clifford (Ph.D.)University of Texas Medical

Branch-Galveston528 Administration BuildingGalveston, TX 77555Tel: (713) 772-4777

Hoyer, LeonAmerican Red Cross430 17th Street, N.W.Washington, DC 20006Tel: (202) 639-3468Fax: (202) 639-3193

40

Hrabowski, Freeman A., III (Ph.D., M.A., B.A.)PresidentUniversity of Maryland,

Baltimore County1000 Hilltop CircleBaltimore, MD 21250Tel: (410) 455-3880Fax: (410) 455-1210hrabowski@umbc.edu

Hunt, Neen (Ed.D.)Executive DirectorAlbert and Mary Lasker

Foundation110 East 42nd Street, Suite 1300New York, NY 10017Tel: (212) 286-0222Fax: (212) 286-0924nhunt@laskerfoundation.org

Ionescu-Pioggia, Martin (Ph.D.)Program OfficerBurroughs Wellcome Fund21 T.W. Alexander DriveResearch Triangle Park,

NC 27709Tel: (919) 991-5115Fax: (919) 991-0695mionescu@bwfund.org

Jacobs, LindaRockefeller Brothers Fund437 Madison Avenue, 37th floorNew York, NY 10022-7001Tel: (212) 812-4200Fax: (212) 812-4299rock@rbf.org

Jarmul, DavidDeputy Director of

CommunicationsHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8857Fax: (301) 215-8863jarmuld@hhmi.org

Jordan, Elke (Ph.D.)Deputy DirectorNational Human Genome

Research Institute31 Center Dr., Building 31,

Room 4B09Bethesda, MD 20892-2152Tel: (301) 496-0844Fax: (301) 402-0837ej10d@nih.gov

Kahn, RichardAmerican Diabetes Association1701 N. Beauregard St.Alexandria, VA 22311Tel: (703) 549-1500Fax: (703) 836-7439

Karlin, TrishElizabeth Glaser Aids Foundation2950 32nd Street, Suite 125Santa Monica, CA 90405Tel: (310) 314-1459Fax: (310) 314-1469trish@pedaids.org

Katona, Peter G. (Sc.D.)President, Biomedical

EngineeringThe Whitaker Foundation1700 N. Moore St., Suite 2200Rosslyn, VA 22209Tel: (703) 528-2430Fax: (703) 528-2431katona@whitaker.org

Kelly, Melinda (Ph.D.)Paralyzed Veterans of America801 18th Street, N.W.Washington, DC 20006Tel: (202) 416-7652Fax: (202) 416-7641

Klippel, JohnArthritis Foundation1330 West Peachtree StreetAtlanta, GA 30309

Koerner, T.J. (Ph.D.) Director of Research Information

ManagementAmerican Cancer Society1599 Clifton Rd.Atlanta, GA 30329Tel: (404) 329-7702Fax: (404) 321-4669

Korn, David (M.D.)Senior Vice PresidentAssociation of American Medical

Colleges2450 N. Street, N.W.Washington, DC 20037Tel: (202) 828-0509Fax: (202) 828-1125dkorn@aamc.org

Levi-Pearl, SueDirector, Medical and Scientific

ProgramsTourette Syndrome Association, Inc.42-40 Bell BoulevardBayside, NY 11361-2820Tel: (718) 224-2999Fax: (718) 279-9596tourette@ix.netcom.com

Lichtman, Marshall A., (M.D.)Executive Vice President for

Research and Medical AffairsThe Leukemia & Lymphoma SocietyProfessor of Medicine and of

Biophysics and BiochemistryUniversity of Rochester School of

Medicine and DentistryUniversity of Rochester Medical

Center601 Elmwood Ave., Box 610Rochester, NY 14642Tel: (716) 275-2205Fax: (716) 271-1876mal@urmc.rochester.edu

Lifton, Richard P. (M.D., Ph.D.)Associate Investigator, Howard

Hughes Medical InstituteYale University School of Medicine295 Congress Avenue,

BCMM 154DNew Haven, CT 06519Tel: (203) 737-4420Fax: (203) 737-1761

Liu, Dennis WC. (Ph.D.)Program DirectorHoward Hughes Medical Institute4000 Jones Bridge Rd.Chevy Chase, MD 20815-6789Tel: (301) 215-8734Fax: (301) 215-8888dliu@hhmi.org

Appendix C: Participants 41

Marcus, RobertThe Marcus Foundation, Inc.2455 Paces Ferry Rd., Bldg. C,

22nd floorAtlanta, GA 30338-4024

McCormick, Mary (Ph.D.)Senior Program AnalystPostdoctoral Research Fellow-

ships for PhysiciansHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8882Fax: (301) 215-8888mccormic@hhmi.org

McGovern, Victoria (Ph.D.)Program OfficerBurroughs Wellcome FundP.O. Box 1390121 T.W. Alexander DriveResearch Triangle Park, NC 27709Tel: (919) 991-5112vmcgovern@bwfund.org

McNally, Len (M.S., M.P.H.)Program DirectorNew York Community Trust2 Park AvenueNew York, NY 10016Tel: (212) 686-0010 Ext. 556Fax: (212) 532-8528lm@nyct-cfi.org

Mertle, MelissaAmerican Association for the

Advancement of Science1200 New York Avenue, N.W.Washington, DC 20005Tel: (202) 326-6400

Miller, Carolyn Branch Chief, External Systems

BranchNational Science Foundation4201 Wilson Blvd. - DIS, Room

455Arlington, VA 22230Tel: (703) 306-1145 ext.4659Fax: (703) 306-0243

Moore, SuzanneAmerican Association for the

Advancement of Science1200 New York Avenue, N.W.Washington, DC 20005Tel: (202) 326-6400

Nochumson, Howard (M.A.)Executive Director Washington Square Health

Foundation, Inc.875 North Michigan Ave., Suite 3516Chicago, IL 60611Tel: (312) 664-6488Fax: (312) 664-7787nochumson@wshf.org

O’Donnell-Tormey, Jill (Ph.D.)Executive DirectorCancer Research Institute681 Fifth AvenueNew York, NY 10022Tel: (212) 688-7515 ext.223Fax: (212) 832-9376jillotcri@aol.com

Osborn, June E. (M.D.)PresidentJosiah Macy, Jr. Foundation44 East 64th St.New York, NY 10021Tel: (212) 486-2424Fax: (212) 644-0765jeosborn@aol.com

Peck, Martha (M.Sc.)Vice President, Programs and

CommunicationsBurroughs Wellcome Fund21 T.W. Alexander DriveP.O. Box 13901Research Triangle Park,

NC 27709-3901Tel: (919) 991-5102Fax: (919) 991-5160mpeck@bwfund.org

Pellegrini, Maria (Ph.D.)Program DirectorW.M. Keck Foundation555 South Flower Street,

Suite 3230Los Angeles, CA 90071Tel: (213) 680-3833Fax: (213) 614-0934mpelligrini@wmkeck.org

Perpich, Joseph G. (M.D., J.D.)Vice President for Grants and

Special ProgramsHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8890Fax: (301) 215-8888perpichj@hhmi.org

Preston, Lorri J. (M.P.H.)Director, Medical and Scientific

CommunicationsAmerican Cancer Society1599 Clifton Rd.Atlanta, GA 30329Tel: (404) 329-7775Fax: (404) 329-5787lpreston@cancer.org

Probert, Edward W. (LL.B.)President and CEOFannie E. Rippel Foundation180 Mount Airy Rd., Suite 200Basking Ridge, NJ 07920-2021Tel: (908) 766-0404Fax: (908) 766-0527rippel@gti.net

Racher, Susan M. (M.B.A.)Chief Financial OfficerThe Wallace H. Coulter Foundation790 NW 107th Ave., Suite 215Miami, FL 33172Tel: (305) 559-2991Fax: (305) 559-5490susanracher@whcf.org

Read, WilliamFlinn Foundation3300 North Central AvenueSuite 2300Phoenix, AZ 85012-2513

Robertson, Rose Marie (M.D.)Professor of MedicineAssociate Director of CardiologyVice Chair for Academic AffairsVanderbilt University Medical

Center1211 22nd Ave. SouthNashville, TN 37232

42

Rubinstein, EllisEditor, Science1200 New York Avenue, N.W.Washington, DC 20005Tel: (202) 326-6596

Ruffin, John (Ph.D.)Associate Director for Research

on Minority HealthNational Institutes of Health1 Center Drive, MSC 0164Bethesda, MD 20892-0164Tel: (301) 402-1366Fax: (301) 402-7040ruffinj@od.nih.gov

Sandy, Lewis G. (M.D.)Executive Vice PresidentThe Robert Wood Johnson

FoundationP.O. Box 2316Princeton, NJ 08540Tel: (609) 243-5940Fax: (609) 243-5894lsandy@rwjf.org

Schaffer, Walter T. (Ph.D.)Research Training OfficerNational Institutes of Health6701 Rockledge Drive, Room 6184Bethesda, MD 20892-7911Tel: (301) 435-2687Fax: (301) 480-0146ws11q@nih.gov

Schwartz, AnneVice PresidentGrantmakers In Health,1100 Connecticut Avenue, N.W.

Suite 1200Washington, DC 20036Tel: (202) 452-8331Fax: (202) 452-8340

Scott, MelanieProgram and Database SpecialistBurroughs Wellcome FundP.O. Box 1390121 T.W. Alexander DriveResearch Triangle Park, NC 27709Tel: (919) 991-5107Fax: (919) 991-5167mscott@bwfund.org

Sewer, Marion (Ph.D.)Department of BiochemistryVanderbilt UniversityLight Hall, Room 606Nashville, TN 37232-0146Tel: (615) 343-0146marion@toxicology.mc.vanderbilt

Shapiro, Bert (Ph.D.)National Institute of General

Medical SciencesNational Institutes of Health45 Center Drive, MSC 6200Building 45-Room 2AS.13ABethesda, MD 20892-6200Tel: (301) 594-3830Fax: (301) 480-2004shapirob@gml.nigms.nih.gov

Sharpe, Richard S.Senior Program OfficerDonald W. Reynolds Foundation1701 Village Center CircleLas Vegas, NV 89134Tel: (702) 804-6023Fax: (702) 804-6035richard.sharpe@dwrf.org

Shimamura, Akiko (M.D., Ph.D.)Instructor in PediatricsDana Farber Cancer Institute,

Pediatric OncologyChildren’s Hospital, Pediatric

Hematology/OncologyHarvard Medical School,

Department of Cell BiologyHarvard Medical School240 Longwood Ave.Boston, MA 02115Tel: (617) 632-5284 Fax: (617) 432-1144ashimamura@hms.harvard.edu

Shoemaker, JohnPrevent Blindness America500 East Remington RoadSchaumberg, IL 60173

Silverstein, Samuel C. (M.D.)Board Member, Cancer Research

FundJohn C. Dalton Professor and

ChairmanDepartment of Physiology and

Cellular BiophysicsColumbia University630 West 168th StreetNew York, NY 10032Tel: (212) 305-3546Fax: (212) 305-5775scs3@columbia.edu

Simchowitz, Louis (M.D., M.B.A.)Senior Program OfficerGraduate Science Education

ProgramOffice of Grants and Special

ProgramsHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8590 or 8884 Fax: (301) 215-8888simchowitz@hhmi.org

Steele, Tara (B.A.)President and CEOGlaucoma Research Foundation200 Pine Street, Suite 200San Francisco, CA 94115Tel: (415) 986-3162Fax: (415) 986-3763tsteele@glaucoma.org

Stevens, John (M.D.)Vice President for Extramural

GrantsAmerican Cancer SocietyResearch Department1599 Clifton Road, N.E.Atlanta, GA 30329Tel: (404) 329-7550Fax: (404) 321-4669jstevens@cancer.org

Appendix C: Participants 43

Stone, George (Ph.D.)Chief, Commons, Extramural

Inventions, and TechnologyResources Branch

National Institutes of Health6705 Rockledge Drive, Room 1136,

MSC 7980Bethesda, MD 20892-7980Tel: (301) 435-1986Fax: (301) 480-0272

Sturman, Lawrence S. (M.D., Ph.D.)Program Advisor The Aaron Diamond Foundation

& The Irene Diamond FundWadsworth Center – New York

State Department of HealthEmpire State Plaza, P.O. Box 509Albany, NY 12201-0509Tel: (518) 474-7592Fax: (518) 474-3439lawrence.sturman@wadsworth.org

Sumilas, Michele (M.P.H.)Washington RepresentativeAmerican Federation for Medical

Research227 Massachusetts Ave, N.E.,

Suite 303Washington, DC 20002Tel: (202) 543-7032Fax: (202) 543-7062msumilas@afmr.org

Sung, Nancy (Ph.D.)Program OfficerBurroughs Wellcome FundP.O. Box 13901Research Triangle Park,

NC 27709-3901Tel: (919) 991-5100Fax: (919) 991-5160nsung@bwfund.org

Tallquist, Michelle (Ph.D.)Senior Research FellowFred Hutchinson Cancer

Research Center1100 Fairview Ave. N. P.O. Box 19024, A2-025Seattle, WA 98109Tel: (206) 667-6826Fax: (206) 667-6522mtallqui@fhcrc.org

Taylor, Timothy C. (Ph.D.)Fellowship AdministratorGraduate Science EducationHoward Hughes Medical Institute4000 Jones Bridge RoadChevy Chase, MD 20815-6789Tel: (301) 215-8879Fax: (301) 215-8888taylort@hhmi.org

Teitelbaum, Michael S. (Ph.D.)Program DirectorAlfred P. Sloan Foundation630 Fifth Avenue, Suite 2550New York, NY 10111-0242Tel: (212) 649-1649Fax: (212) 757-5117teitelbaum@sloan.org

Tomatis, Luis (M.D.)President and CEOVan Andel Institute201 Monroe N.W., Suite 400Grand Rapids, MI 49503Tel: (616) 235-8242Fax: (616) 235-8245luis.tomatis@vai.org

Tso, DanielThe Melanoma Research Foundation23705-5 El Toro Road #206Lake Forest, CA 92630Tel: (800) 673-1290

Van, Susan (M.A.)PresidentThe Wallace H. Coulter Foundation790 NW 107th Ave., Suite 215Miami, FL 33172Tel: (305) 559-2991Fax: (305) 559-5490

van der Willik, OdetteDirector, Grant ProgramAmerican Federation for Aging

Research 1414 Avenue of the AmericasNew York, NY 10019Tel: (212) 752-2327Fax: (212) 832-2298owillik@aol.com or www.afar.org

Vento, RayAmerican Lung Association1740 BroadwayNew York, NY 10019Tel: (212) 315-8788rvento@lungusa.org

Weinberg, Myrl (CAE)PresidentNational Health Council1730 M Street, N.W., Suite 500Washington, DC 20036Tel: (202) 785-3910Fax: (202) 785-5923weinberg@nhcouncil.org

Whittemore, Vicky Holets (Ph.D.)Executive DirectorNational Tuberous Sclerosis

Association8181 Professional Place, Suite 110Landover, MD 20785-2226Tel: (301) 459-9888 or

(800) 225-6872Fax: (301) 459-0394vicky.whittemore@ntsa.org

Wilson, Donella J. (Ph.D.)Scientific Program DirectorAmerican Cancer Society1599 Clifton Rd.Atlanta, GA 30329Tel: (404) 329-7717Fax: (404) 321-4669dwilson@cancer.org

44

American Cancer Society1599 Clifton Road, N.E. • Atlanta, GA 30329

Phone: (800) ACS-2345 • For research grants information: (404) 329-7558www.cancer.org

The American Cancer Society is a nationwide, community-based health organizationdedicated to eliminating cancer as a major health problem by preventing cancer, saving lives from cancer, and diminishing suffering from cancer through research, education, advocacy, and service. It is one of the oldest and largest voluntary healthagencies in the United States, with over two million volunteers working to conquer cancer through balanced programs of research, education, patient service, and rehabilitation. The American Cancer Society, Inc., consists of a National Society withchartered Divisions throughout the country and over 3,400 local Units.

Burroughs Wellcome FundP.O. Box 13901 • 21 T.W. Alexander Drive • Research Triangle Park, NC 27709

Phone: (919) 991-5100 • Fax: (919) 991-5160www.bwfund.org

The Burroughs Wellcome Fund is an independent private foundation dedicated toadvancing the medical sciences by supporting research and other scientific and educational activities. The Fund’s general strategy is to help outstanding scientists earlyin their careers develop as independent investigators and to support investigators whoare working in or entering undervalued or underfunded fields in the basic medical sciences. With its endowment of approximately $670 million, the Burroughs WellcomeFund makes some $35 million in grants annually in the United States and Canada.Based in Research Triangle Park, North Carolina, the Fund was founded in 1955 as thecorporate foundation of the pharmaceutical firm Burroughs Wellcome Co. In 1993, theBurroughs Wellcome Fund became independent from the company, which wasacquired by Glaxo in 1995. The Burroughs Wellcome Fund has no affiliation with the firmnow known as Glaxo Wellcome or with any other corporation.

Howard Hughes Medical Institute4000 Jones Bridge Road • Chevy Chase, Maryland 20815-6789

(301) 215-8500 • www.hhmi.org

The Howard Hughes Medical Institute, the nation's largest private philanthropy, is amedical research organization whose scientists include many of the world's leaders inthe fields of cell biology, genetics, immunology, neuroscience, and structural biology.Howard Hughes Medical Institute Investigators carry out research at universities andacademic medical centers across the United States. In addition, the Institute has agrants program that is the largest private initiative in U.S. history to enhance scienceeducation at all levels from preschool through postgraduate training. Through its grantsprogram, the Institute also supports the research of outstanding biomedical scientistsoutside the United States and provides funding to help medical schools sustain theircommitment to research. The endowment of the Institute by late 1999 was approxi-mately $13 billion. The Institute’s headquarters is located in Chevy Chase, Maryland,just outside Washington, D.C.