Table Of Content

~}QUGHS WELLCOME FUND 1999 ANNUAL REPORT HUAI 22503548417 BURROUGHS WELLCOME FUND The Burroughs Wellcome Fund is an independent private foundation dedicated to advancing the medical sciences by supporting research and other scientific and educational activities. 1999 ANNUAL REPORT BURROUGHS WFEULNLDC OMFE e 1999 ANNUAL REPORT CONTENTS PND OI TATHE. DURROUGHS: VV ELEC OMENELIND g tree te ne te eee cote VRE te lene x ie aria till Gus aeRO aS 2 FECL TEs OWT ELEN Eei eF ESL E) EL ue eee no ame Pe | Re 9 Se aS Tile yee len RE Roh ig acd GRO SiR We 3 GENERATING NEW MEDICAL KNOWLEDGE: GMUNICAE SCIENTISINA WARDS INu) RANSLATIONALY RESEARCH tins Satu A. Sua Aaions ms ooh ke meen 526 1] MINDERSTUDIED INFECTIOUS DISEASES" HELP FROM GENOMICS @3¢.¢245 ao ssa ods obacesgecier se seneenes 19 |P USTUOa R TONS ES RNIN SS DA ous Cuetec aly We nth) on anaes eRe el ome ar ae ea ne ee i a BA| PN ONGIAIaS TATE MENTSOAND 2A DDITIONAL INPORMATIONGS cee ekaee trace eee tae sett athlec heads ose mead eods 22 CRATES SLND: ene ae ee ra eta ret Rh See tN LBW NARA dle king. Stine 30 PEE NEATION. EORGA PPL ICAINT S saneraee teeta Ty mn Ee ee Sea tn cries ares dene Soe bysle Oe > 68 PROGA AEA PEL LOAT IONS) SIDE LINELS steppe ae ieee te a tec TRON Prd AE eon NN it niea ais ie stern nw ee err Hle-e ies 74 PONS Ry CONNETelR EE S eee ete Oe re Re Be Fee CM Ry Boneh raat N Birkys Faroe, wieb n gale ys TB) GAC OR DIRECTOR Seas ee Be Rn ree ee ese ANAM rE Moon wes oa UbIR Nae OAL eR ene a 81 errr Ne a Mn at PD IO Wr Dae REE Ie AnD aeo tter Nac RU Ie aise mesa vais ne ocd ale we oe & Ses 83 RGONTACT INFORMATION. POR MAJOR PROGRAMS a3 cusieil fice canis ssa oo aid in Bid stile ehiens oe cha iees ele ee oes 86 Burroughs Wellcome Fund 21 T. W. Alexander Drive Post Office Box 13901 Research Triangle Park, NC 27709 Telephone (919) 991-5100 Depicted in BWF’s logo, the eye Fax (919) 991-5160 of the ancient god Horus is widely www.bwfund.org considered a symbol of health ABOUT THE BURROUGHS WELLCOME FUND The Burroughs Wellcome Fund was founded in 1955 as. the corporate foundation of Burroughs Wellcome Co., the U.S. branch of the Wellcome pharmaceutical enterprise, based in the United Kingdom. The Wellcome enterprise was started in 1880 by two young American pharmacists, Henry Wellcome and Silas Burroughs, who had moved to London to manufacture and sell “compressed medicines”—that is, pills—which the pair believed could replace the potions and powders of the day. Their firm prospered. After Burroughs died in 1895, Wellcome directed the growth of the company into an international network with subsidiaries in numerous countries on several continents. As the business grew, Wellcome held firm to his strong belief that research was fundamental to the development of excellent pharmaceutical products—a belief he put into practice by establishing the industry’s first research laboratories. When Wellcome died in 1936, his will vested all of the corporate shares in a new organization—the Wellcome Trust—devoted to supporting research in medicine and allied sciences and to maintaining museums and libraries dedicated to these fields. Over the decades, the Trust grew to become the world’s largest charitable foundation devoted exclusively to the biomedical sciences. In 1955, leaders at the Wellcome Trust and Burroughs Wellcome Co.-USA envisioned an extension of this effort in the United States—and so was born the Burroughs Wellcome Fund. After nearly four decades as a corporate foundation, BWFE in 1993 received from the Trust a $400 million gift that enabled us to become a completely independent foundation, with no direct ties to the founding company. (Nor is BWF affiliated in any way with Glaxo Wellcome Inc., which emerged in 1995 when that firm acquired all of the Wellcome commercial holdings.) With this increase in assets, BWF has been able to play a larger role in funding biomedical research, including extending our support into Canada. In carrying out this work, we are governed by a Board of Directors composed of distinguished scientists and business leaders, and our competitive award programs are directed by advisory committees composed of leading researchers and educators. The importance of curiosity-driven research, as endorsed by Henry Wellcome, continues as our guide. Thus, more than a century after two enterprising American pharmacists set in motion their pioneering partnership, the Burroughs Wellcome Fund remains committed to the belief that fostering research by the best and brightest scientists offers the fullest promise for improving human health. REPORT FROM THE PRESIDENT By Enriqueta C. Bond, Ph.D. The mission of the Burroughs Wellcome Private philanthropy provides such as hospitals and nursing homes; Fund is to advance the medical sciences venture capital that is essential to support of organizations addressing by supporting research and other the progress of medical research. general health issues or specific dis- scientific and educational activities. Investments could be directed to support eases; and a small portion of support Within this broad mandate, we place institutions, facilities or equipment, for medical research. primary emphasis on basic biomedical specific research projects, or the human Grantmaking foundations con- science—tesearch aimed at discovering capital of the biomedical enterprise—the tributed $19.46 billion to nonprofit fundamental knowledge that will individual researcher. In playing this organizations in 1998, representing underpin efforts to improve human catalytic role, private funders may a 22 percent increase over 1997. This health and well-being. find the most success by focusing explosive growth was fueled by the To carry out this mission, BWF’s their efforts—that is, by identifying prolonged bull market and the near- general strategy is to support the opportunities or riskier areas in need record levels of gifts and bequests from development of promising U.S. and of support and then targeting support donors, as well as by the formation Canadian scientists early in their careers within those areas. of new grantmaking organizations. and to support investigators working Since 1980, the number of foundations in or entering areas of science that are has doubled to 44,000. Foundations undervalued or underfunded. Our Private philanthropy currently spend 16.2 percent of total financial support is channeled primarily grant dollars, or $1.2 billion, on health. provides venture capital through competitive peer-reviewed The largest share of health giving, award programs, which encompass six that is essential 58 percent, goes to general and reha- major categories—career development to the progress bilitative services, including hospitals of scientists, emerging infectious and medical care; reproductive health; of medical research. diseases, therapeutic sciences, repro- public health; health policy; and man- ductive science, interfaces in science, agement. Of the health portion, only and science education. To complement Although philanthropic founda- about $265 million, or 22 percent, these competitive programs, we also tions are heterogeneous and provide goes to medical research. In contrast, award grants to nonprofit organizations only a small amount of support in government support for medical conducting activities to improve the comparison to governmental and research was roughly $17 billion and general environment for science. industrial support, they fill a crucial industry support was $18 billion. In this report, I’d like first to survey niche in medical research, and their Philanthropic organizations are the current landscape of philanthropic involvement in this area should be a diverse group, including not only support for health research, and then extended. Foundations, in hand with corporate and private foundations but to describe some of BWF’s activities the scientific community, should also voluntary health organizations and during our previous fiscal year. pursue policies augmenting private medical research organizations. More contributions, and they should recently, conversion health foundations Philanthropies and Health Research educate potential donors about the have emerged from the sale of non- For the past several years, BWF has nature of medical research, about the profit hospitals and private insurers. focused part of our effort on learning value of philanthropic dollars, and Many of the programs conducted by more about philanthropic contributions about ways to leverage such support. philanthropic organizations are small, for health research. Because we Total philanthropic giving for less than $1 million per organization believe so strongly in the value of 1998 came to $174.52 billion, with per year, according to a survey of supporting medical research, BWF $148.46 billion from individuals and 118 funders conducted by the Pew has been networking with other like- bequests, $17.09 billion from noncor- Charitable Trusts, the Burroughs minded foundations to explore oppor- porate foundations, and $8.97 billion Wellcome Fund, the American Cancer tunities and gaps in research funding from corporations. Almost $17 billion, Society, and the Howard Hughes and encouraging others to consider or 9.7 percent, was given for “health.” Medical Institute. Support for post- investing in this vital area. This segment included support of doctoral researchers and beginning health services and health facilities, investigators is especially popular. Graduate training in biomedical and health-related research also is supported. In fiscal 1999, BWF approved overhead or infrastructure; often Voluntary organizations target educa- more than $47.3 million in desire to model and then move on, tional programs for patients and health rather than to provide long-term sus- new grants and paid out professionals. Foundations and medical tained support; and have a tendency research organizations emphasize nearly $26.4 million in grants, to carry out their own programs K-12 and undergraduate life science instead of working collaboratively. both totals greater than in any education. In the current health research Individual giving amounted to year in our 44-year history. environment, funders will have to $134.84 billion in 1998. Given that partner and work more collaboratively about $13 billion more per year could because of the expense of research. be obtained if 10 percent of these programs, BWF is partnering with the Some of the opportunities for action individuals were encouraged to community foundation to establish new by foundations include: contribute to medical research, an programs to support medical students ¢ New paradigms for training institutional mechanism might be and early-career faculty investigators, M.D.s and Ph.D.s to respond to established to provide a “home” and as well as science mentoring. changes in the environment within administrative structure to manage Conversion foundations, estab- managed care organizations, industry, and direct such funds. BWF has lished as nonprofit health institutions and academic health centers. supported the Institute for Science when hospitals or insurers convert ¢ Emerging fields and interdisci- Philanthropy as such a tool, and both to profit-making organizations, offer plinary research (such as genomics the National Institutes of Health and another potential source of health and neuroscience), interfaces in science the U.S. Centers for Disease Control research support. In 1998, there were (such as between mathematics and and Prevention have successfully 109 conversion foundations in 32 states biology or between physics and established foundations that could and the District of Columbia, with biology), and biomedical ethics. be conduits for such funds. Many total combined assets of more than ¢ “Risky” or politically unpopular academic medical centers also are likely $13 billion. If these foundations donated research, such as that in reproductive candidates for individual donations 5 percent of their assets every year, biology and health, substance abuse, from alumni and grateful patients. as private foundations are required to do international health and disease, and Community foundations, which by the federal Internal Revenue Service, social/behavioral issues. derive their support from many donors they would contribute $650 million ¢ Translational clinical research and target their grantmaking within annually for charitable purposes. that speeds results from the research their communities, are likely to benefit Although surveys indicate that bench to the bedside and to other most from increased donor support 65 percent of the conversion foundations clinical research areas, including over the next several years, when a are dedicated principally to “health patient-oriented research, epidemiologic large intergenerational transfer of and health care,” targeted support for and behavioral studies, and outcomes wealth is expected. However, few medical and health research is actually and health services research. community foundations give grants quite limited. These foundations might ¢ Behavioral research, which is for medical research, nor are they direct a larger portion of their grants, essential for preventing and treating viewed as having expertise in this perhaps 5 percent to 25 percent, to disease. area. BWE has established two research yielding better approaches ¢ Public understanding of science health-related research award programs to care for their target populations. to help children and adults grasp its at our local Triangle Community importance. Foundation as models for community- Playing to Our Strengths ¢ New partnerships among acad- based support. These programs—the The strengths of private funders in emic health centers, industry, and George H. Hitchings Fund for Health supporting health research include managed care organizations through Research and Science Education, the ability to move quickly to fill a private-sector initiatives related to and the Gertrude B. Elion Fund for gap, to function as neutral conveners medical research. Health Research—honor pioneering for identification of priorities, to Charitable dollars for medical scientists who played influential roles model successful approaches, to dis- research, though modest, should be in making BWF what we are today. seminate approaches that work, and viewed as essential “risk capital” Dr. Hitchings, who died in 1998, to take risks that may have high for new ideas and new models. But served as BWF’s president from payoffs. On the other hand, private in order to capture more dollars from 1974 to 1990, and Dr. Elion, who funders have limited funds to commit private philanthropy, the scientific died in 1999, served on our Board to research; are less willing to support of Directors since 1991. In both community must make a stronger case in neuromuscular disease. Twenty-four since an important program goal is for the relevance of medical research; biomedical scientists early in their to help awardees achieve research underscore the critical, catalytic role careers received Career Awards in the independence and secure a faculty that even such modest support plays; Biomedical Sciences. Working across position. and support policies that foster chari- a range of disciplines, these researchers In another career-development table contributions. Members of the share a common goal: discovery of program, BWE awarded Hitchings- scientific community should work basic knowledge that ultimately will Elion Fellowships to five postdoctoral more closely with advocacy organiza- lead to improvements in human health scientists in the biomedical and tions, such as Research! America and and well-being. The awards, which behavioral sciences. The fellowships, Funding First; with their professional totaled approximately $12 million, named for the two Nobel Laureates societies, such as the American are intended to foster the development who were long associated with BWF, Association for the Advancement of and productivity of these promising enable U.S. and Canadian scientists Science (AAAS) and the Federation researchers and help them make the to train for up to three years in labo- of American Societies for Experimental critical transition to becoming inde- ratories in the United Kingdom or the Biology; with their universities and pendent investigators. It is expected Republic of Ireland and then return to academic medical centers; and with that by the end of the award period, a North American university to set up their honorary institutions, such as which ranges from four to six years, their own research programs. Beginning the National Academy of Sciences recipients will be engaged in productive with the 2001 award series, these fellow- and the Institute of Medicine, to make research programs and will be able ships will be merged with our Career a concerted case for greater philan- to compete effectively for support Awards in the Basic Medical Sciences, thropic support of medical research. from government and other extramural to enhance that program’s international From this look at what the future sources. training component. could bring, with proper nurturing and BWE also awarded Research Travel cooperation, let’s step back to review Grants to 57 U.S. and Canadian some of BWF’s recent activities. Working across a range researchers, including six researchers in the history of medicine, to enable of disciplines, BWF career Overview of BWF Programs them to visit colleagues in the United In fiscal 1999, BWE approved more award recipients share a Kingdom or Ireland for shorter periods than $47.3 million in new grants and common goal: discovery (2 weeks to 6 months) in order to paid out nearly $26.4 million in grants, participate in collaborative research of basic knowledge that will both totals greater than in any year projects or learn new research tech- in our 44-year history. We supported underpin broader efforts niques. These grants are intended approximately 600 active grants (new to facilitate the rapid exchange of to improve human health and continuing) at more than 200 knowledge and to promote collabora- academic and other nonprofit institu- and well-being. tion among scientists in the countries tions across the United States and involved. Canada. Some 90 percent of these A guiding principle of BWF’s grants were awarded through our BWE initiated this program in grantmaking is that fostering the specially designated competitive 1995, and we now have made a total careers of our awardees extends well award programs, with most of the of 101 awards—an investment of more beyond the grant support provided. awards earmarked for individual than $50 million in the careers of bio- At the 1999 convocation of career- scientists nominated by their institu- medical investigators. With the 1999 development awardees, the program tions. By program area, here are some awards, the program is essentially at was shaped to provide networking of the year’s highlights: steady state, and this increased critical opportunities and a chance to explore mass brings the opportunity to assess such critical career development CAREER DEVELOPMENT outcomes. Initial data—collected topics as how to negotiate a faculty OF SCIENTISTS through annual surveys, awardee position, lab management, academic- progress reports, and regular meetings industry collaboration, dual-career They are probing the signaling with awardees and members of the couples, and issues facing women in systems in neurons that might go awry program advisory committee—look science. BWF will be issuing a special in long-term depression, decoding favorable. For the 1995 and 1996 report on our career development rhythms in the nervous system, and awardees, 93 percent and 100 percent, programs by early summer of 2000. studying the role of muscle proteins respectively, have received tenured faculty appointments—good news, Since postdoctoral students and By supporting a cadre gravity” of these projects will be in junior faculty who hope to succeed of early- and midcareer the developing world, where bacterial, in science need to uncover the secrets viral, fungal, and parasitic diseases of funding, networking, and the peer- investigators, BWF hopes cause significant morbidity and mor- review process, BWE has helped to bring new thinking and tality. Initial plans call for two rounds support the launch of a new Career of awards. During the first round, com- research approaches to Development Center on the World pleted in the fall of 1999, seven awards Wide Web that will address many of the areas of molecular totaling approximately $18 million these mysteries. The center is part went to groups working in a variety parasitology and mycology. of Science’s Next Wave, which is of countries, including Peru, Egypt, and administered by the AAAS (and which Nigeria, and on a variety of maladies, BWE helped support in its early days). including tuberculosis, hepatitis C, Access is free, and the Web address Two scholar awards and four new leishmaniasis, and sexually transmitted is http://nextwave.sciencemag.org/ investigator awards went to scientists diseases. Competition for the next feature/careercenter.shtml. working in molecular parasitology, round of awards will be announced The center, which is cofunded and two scholar awards and six new in early 2000. by the Howard Hughes Medical investigator awards went to scientists Three ad hoc initiatives also Institute, includes features on such working in molecular pathogenic deserve special mention. The first is topics as grant writing and grant mycology. The awardees are designing an international effort begun in 1996 management, how to set up and inhibitors to thwart the parasite to sequence the genome—that is, to maintain a laboratory, how to nego- Trypanosoma brucei, which plagues identify the order of all the chemical tiate for space, and how to assemble Africa and South America and causes building blocks in the genetic code— a staff. It offers insight into what the disease trypanosomiasis, and they of Plasmodium falciparum, the most makes a good proposal and how goy- are exploring how the body’s sensi- dangerous form of the parasite that ernment agencies make funding deci- tive endothelial cells respond when causes malaria. (See the article begin- sions, and a “GrantDoctor” column infected by Candida albicans, a fungus ning on page 19 for more information.) addresses such issues as how to appeal that can prove deadly for individuals Initially, BWF joined with the a grant proposal that has been reviewed whose immune systems have been Wellcome Trust and, in the United unfavorably. The site also offers a damaged by disease or other factors, States, with the National Institute “reading list” of online reprints and among other projects. of Allergy and Infectious Diseases selected resources associated with Malaria, which annually claims and the Department of Defense in postdoctoral and junior faculty career more than 2 million lives worldwide, supporting the Malaria Genome development, and it includes a concise is targeted for special support through Project. Recently, the World Health bibliography of offline references. our New Initiatives in Malaria Research Organization, with its current “Roll program. This year’s awardees are Back Malaria Program,” signed on EMERGING INFECTIOUS DISEASES working to discover new drug targets, as a funding partner. The project’s developing a better understanding of researchers have completed the BWF’s award programs target what causes drug resistance, investi- sequencing of two of the parasite’s parasitic and fungal pathogens, which gating mosquitocidal toxins, and 14 chromosomes, or the thin strands of despite advances in knowledge of their building a database of genetic and DNA that form the genetic “roadmap,” basic pathology continue to claim biochemical information about malaria. and sequencing of the remaining millions of lives annually. By sup- Beyond BWF’s award programs, chromosomes is progressing well. porting a cadre of early- and midcareer we teamed with the Wellcome Trust The information being generated investigators, BWF hopes to bring new (our sister philanthropy in the United already is proving useful to the thinking and research approaches to the Kingdom) in sponsoring a new trilat- biological community in its search areas of molecular parasitology and eral program to support collaborative for new targets for drug and vaccine mycology. We believe that work on programs in infectious diseases of development, as well as for better these diseases is rich in opportunity for major health importance in the devel- understanding of the pathogenesis achieving fundamental advances, and oping world. The program is “trilateral” of this dreaded disease. that foundations may be able to apply in that it aims to foster existing or new A second BWF effort is jump- just enough support at certain critical collaborations among researchers in starting research efforts to sequence points to shift the balance toward a a developing country and researchers the genomes of several pathogenic positive payoff for human health. in the United States, Canada, or the fungi. This has provided an opportunity United Kingdom. The “center of