2
Where Are We Now?

As noted in many other studies and reports, academic biomedical research is changing (e.g., NRC, 1998; COSEPUP, 2004). What was once the exclusive domain of individual scientists is being supplemented by large teams of scientists. Where there once was collaboration between individual research groups, now networks and consortia include scientists spread around the world. What was once exclusively the realm of biologists and biochemists now includes physicists, mathematicians, computer scientists, and engineers working together in interdisciplinary teams. Where basic and clinical research were once separate domains, they are now integrated into single research programs. Where there was once a well-defined academic career path and plenty of research positions, there is now a complex network of multiple careers paths and career transitions. Each of these changes has relevance for the issues confronting new investigators.

The effect of “big science” on traditional investigator-initiated “small science” in the biomedical sciences has been discussed for over 20 years (e.g., Alberts, 1985). With more collaborative research projects involving tens or hundreds of scientists, often at multiple locations, crediting individual researchers for their contributions to the team effort has become a challenge. In fact, growth in NIH funding for research centers has out-stripped that for research project grants by over 30 percent between 1998 and 2005 (Check, 2004). This trend toward research center funding is especially important for new investigators who are unlikely to serve as principal investigator (PI) or even leader of a collaborating team.



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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research 2 Where Are We Now? As noted in many other studies and reports, academic biomedical research is changing (e.g., NRC, 1998; COSEPUP, 2004). What was once the exclusive domain of individual scientists is being supplemented by large teams of scientists. Where there once was collaboration between individual research groups, now networks and consortia include scientists spread around the world. What was once exclusively the realm of biologists and biochemists now includes physicists, mathematicians, computer scientists, and engineers working together in interdisciplinary teams. Where basic and clinical research were once separate domains, they are now integrated into single research programs. Where there was once a well-defined academic career path and plenty of research positions, there is now a complex network of multiple careers paths and career transitions. Each of these changes has relevance for the issues confronting new investigators. The effect of “big science” on traditional investigator-initiated “small science” in the biomedical sciences has been discussed for over 20 years (e.g., Alberts, 1985). With more collaborative research projects involving tens or hundreds of scientists, often at multiple locations, crediting individual researchers for their contributions to the team effort has become a challenge. In fact, growth in NIH funding for research centers has out-stripped that for research project grants by over 30 percent between 1998 and 2005 (Check, 2004). This trend toward research center funding is especially important for new investigators who are unlikely to serve as principal investigator (PI) or even leader of a collaborating team.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research There is growing interdisciplinarity in biomedical research with physical scientists, computer scientists, and engineers working with biologists in research areas traditionally the exclusive domains of biology. As suggested by Dr. Zerhouni in his remarks at the committee’s June 2004 workshop, pathways are needed to move physical scientists into biomedical research and to provide opportunities for building interdisciplinary research teams. Moreover, opportunities for moving between and among increasingly overlapping disciplines need to be available to early-career scientists as well as those who have already established their independent disciplinary research program. Biomedical career pathways have traditionally been viewed as linear progressions with individuals moving directly from graduate school to postdoctoral positions to assistant professorships, then obtaining funding and tenure. Regardless of how accurate this view was in the past, clearly this linear pathway is far less common today. The system by which established scientists “clone themselves” through their postdocs and graduate students is increasingly challenged by new, different directions and objectives. Many people who receive PhDs in biomedical sciences opt to pursue careers outside of academic research: in industry, biotechnology, investment, policy, teaching, writing, or any number of other sectors. And there is significantly more movement in and out of the research career track; individual scientists move between disciplines; they take time out for family or to work outside scientific research. Figure 2-1 shows the complexity of the current network of career trajectories in biomedical research. The figure illustrates the many pathways to achieve independence; focusing on only a single pathway puts artificial limits on who may become an independent investigator. Therefore, research funding and training opportunities now need to fit the needs of a variety of careers and allow for transitions among different areas of research. The availability of research funding drives not only the specific research questions investigated, but also the scientific workforce available to carry out that research. NIH grant programs can stimulate the creation of new research positions by providing partial or full salary support. While non-tenure-track “soft-money” positions especially depend on external sources for salary support, a significant number of tenure-track faculty also depend upon grant funding. For instance, a study of the Association of American Medical Colleges (AAMC) indicated that tenure does not carry any financial guarantee for basic science appointments at 30.8 percent of medical schools in 2002, up from 24.4 percent just 3 years earlier. And the percentage of medical schools indicating that tenure guarantees total institutional salary for basic sciences faculty dropped from 38.6 percent in 1999 to 21.7 percent in 2002 (Liu and Mallon, 2004).

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research FIGURE 2-1 Complex network of current career pathways to independent investigator. The former linear pathway from undergraduate to PhD student in the biomedical sciences to postdoc to assistant professor to independent investigator has been replaced by a complex network with many paths to multiples types of independent research.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research GRANT SUCCESS BY AGE Each year, both new and experienced investigators compete in a Darwinian-like system (Freeman et al., 2001) for the portion of the NIH extramural budget not already committed to continuing awards. According to Norka Ruiz Bravo, NIH associate director for extramural research, the youngest investigators (ages 35 or younger) have the highest R01 and R29 success rates (Figure 2-2), though it may take a resubmission and more than one study section round for success. That is, of the age cohorts applying for NIH research awards (Figure 2-3), those 35 and under are funded a greater percentage of the time than those in older age cohorts. But that may include multiple grant proposals, resubmissions, and rounds of peer review. Nonetheless, the average age at which investigators receive their first independent research support is creeping upward (in 2002, age 42 for PhDs and age 44 for MDs) (see Figure 2-4). The average age at which investigators receive their first faculty appointments at U.S. medical schools shows the same trend (in 2002, age 38 for PhDs and age 37 for MDs) (data from the AAMC Faculty Roster as of March 31, 2004; Figure 2-4). FIGURE 2-2 Success rate of competing new R01 and R29 grant application by age of principal investigator. Source: Office of Extramural Research, NIH.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research FIGURE 2-3 Number of R01, R23, R29, or R37 applicants by age cohort. Source: Office of Extramural Research, NIH. The number of biomedical tenure-track faculty in the 33–34 age cohort decreased by half between 1985 and 2001 even though the number of eligible PhD recipients increased during that period (NRC, 2005). But even though the increasing age at receipt of first award seems to follow the increasing age of obtaining the faculty position, a 4–7 year lag persists between becoming a faculty member and receiving a first R01. It should be noted that the data on grant success at NIH differ significantly between different institutes and centers (ICs). In fact, the absolute number of new investigators receiving R01 awards from some ICs has declined significantly over the last few years (for example, the National Cancer Institute, which was the largest supporter of new investigators in the mid- and late-1990s has had more than a 15 percent decline in the number of new investigators supported between 1997 and 2002). New and previously funded investigators both seem to be awarded grants at approximately the same age at which they apply (Table 2-1). However, while there may not be evidence of explicit discrimination against younger investigators in the grant process (Goldman and Marshall, 2002), it may take one or more resubmissions for funding; even one resubmission may introduce a 2-year delay in receipt of finding (Coleman, 2005). NIH still holds at least partial responsibility for the increasing age at which biomedical researchers receive their independence. The current

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research FIGURE 2-4 Average age at time of first assistant professorship at U.S. medical schools and receipt of first R01/R29 award. (a) PhD holders. (b) MD holders. (c) MD/PhD holders. Source: AAMC Faculty Roster Data, as analyzed by Office of Extramural Research, NIH (age at first faculty appointment); Office of Extramural Research, NIH (age at receipt of first NIH award).

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research TABLE 2-1 Average Age for Applicants and Awardees for Competing Awards for New and Previously Funded Investigators. Source: Office of Extramural Research, NIH   Applicants Awardees All applicants 48 47 New investigators (previously unfunded) 44 43 Previously funded 52 50 NIH research funding system may have direct and indirect effects on the progression of researchers through the early stages of their careers: direct in the lack of realistic funding opportunities for new investigators to establish their independence, and indirect in the distribution of independent positions influenced by funding policies and programs. The success of new investigators did not improve despite a doubling of the NIH budget (1998–2003). Even with more money available, no evidence indicates that new investigators received a larger share of funds as a result (in fact, Figure 1-4 shows a decreasing percentage of awards made to new investigators in recent years). Rather, it seems that those with existing funding and established research programs received increased funding, in part to hire additional postdoctoral and graduate student researchers and further exacerbate the imbalance between trained researchers and available positions (Freeman, 2004). In an effort to provide incentives and opportunities for new investigators, NIH has implemented two changes. First, new investigators are designated for special treatment in peer review and in funding decisions by identifying themselves as such on their grant application (referred to as “self-designation”; Figure 2-5). Second, NIH developed the following programs of special relevance for new investigators: R23 New Investigator Research and R29 FIRST Awards: These grants were designed specifically for and restricted to new investigators to support the first few years of a faculty position. They are now discontinued, for reasons described below. R03 Small Research Grant (pilot): These grants are small ($50,000 for direct costs per year for 2 years) and support self-contained studies. Some institutes use them as a way for new investigators to enter the system. R21 Exploratory/Development Grant: These grants are for a total

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research FIGURE 2-5 Instructions for PHS 398. U.S. Department of Health and Human Services Public Health Service Grant Application (PHS 398) Part I Instructions. OMB 0925-0001. Rev. 09/2004.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research FIGURE 2-6 First NIH award for new investigators. The figure shows that the R23 and R29 grants specifically created for new investigators are being replaced by the R21 award, whose purpose is generally not specific for new investigators. Also notice the declining percentage of new investigators receiving R01s as their first award over the last several years. Source: Office of Extramural Research, NIH. of $275,000 in direct costs for 1 to 2 years (but no more than $200,000 in a single year) and support the early stages of exploratory and developmental research projects. K Awards: These awards support career development for research or health professional doctorates. R03 and K awardees have higher success rates in applying for subsequent R01 awards than do those with no prior awards.1 It appears that R21 recipients have no greater success at subsequent R01s (data from Office of Extramural Research, NIH, not shown). Yet, the R21 now appears to be the first NIH award for many new investigators (Figure 2-6). Historically, the R23 New Investigator Award was popular among new investigators until its demise. Then its replacement, the R29 FIRST Award took over as a popular award for new investigators. With the elimination of the R29 (see below for the reasons for this 1   Although the advantage might derive from the fact that those who have received these awards are still considered to be “new investigators” for R01 purposes.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research elimination), new investigators are turning to the R21 exploratory/development grant, even though it is not specifically designed to support new investigators. The appeal of the R21 may be that it does not require discussion of preliminary data and is, therefore, seen as easier to obtain for new investigators. NIH analysis shows that new investigators are entering the system at a higher rate than experienced researchers are leaving it. From 1980 to 1998, the average ingress rate for new investigators was 11.0 percent, and the average egress rate for experienced investigators was 8.4 percent (see Figure 2-7). In particular, researchers appear to stay in the funding system later and later. Investigators over age 55 received 22.7 percent of research awards in 2003, up from only 9.7 percent in 1980 (Figure 1-2). The age distribution of those receiving competing NIH research awards has been increasing with few individuals under age 40 now receiving awards. In 2003, for instance, only 16.9 percent of those receiving R01, R29, or R37 awards were age 40 or younger, a significant decrease from the 50.4 percent in 1980 (see Figure 1-2). The average age of first-time research grant recipients is quite consistent across institution types. Recipients of first research grants average 43 years of age at medical schools and research institutions and 42 at non-medical school academic environments and hospitals (data from Fiscal Year 2003 provided by NIH). The average age of first-time recipients of FIGURE 2-7 Entry and egress rates of NIH research project grant investigators. Source: Office of Extramural Research, NIH.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research awards involving human subjects and those without human subjects involvement differs slightly (overall, 43 for human subjects, 41 without). Some gender differential exists across various NIH grant programs. Although men are, on average, a half-year younger than women (42.26 for men vs. 42.82 for women) at receipt of first award, the difference is reversed—and more pronounced—for the R15 and R21 awards. For the R21, in particular, women are over 2 years younger than their male colleagues at receipt of first award (40.45 for women, 42.60 for men). PhD holders are, on average, younger (41.38±7.30) than either MD/PhD (43.79±6.49) or MD (43.83±6.54) holders at receipt of first NIH research award (data provided by NIH). Not only chronological age demonstrates the difficulties for new investigators. For instance, in its 1997 survey, the American Society for Cell Biology (ASCB) found that 71 percent of those receiving PhDs before 1970 obtained grant funding from the NIH, NSF, or American Cancer Society on their first attempt. That number drops to 43 percent of those graduating in the 1980s and 25 percent of those graduating in the 1990s (Marincola and Solomon, 1998a; http://www.ascb.org/survey/survey.htm). DEMOGRAPHIC DATA A demographic analysis of available data2 provides some insight on why the number of awards to new investigators is so low and has declined over time (see Figure 1-3). How have PhDs ages 35 and younger and educated in the United States fared in recent years? Data presented by Paula Stephan about U.S. PhD recipients from 1993 to 2001 reveal the following: The number of life scientists ages 35 and younger increased 59 percent (see Figure 2-8) The number of life scientists ages 35 and younger in tenure-track positions increased 6.7 percent, and The number of life scientists ages 35 and younger in tenure-track positions in Research I institutions3 declined 12.1 percent (from 618 to 543). 2   As discussed in several places throughout the report, the available data are not always what is needed. Box 2-1 summarizes the major data sources for information on the biomedical workforce. 3   The Carnegie Classification of Institutions of Higher Education is the leading typology of American colleges and universities. It is the framework in which institutional diversity in U.S. higher education is commonly described. Research I institutions offer a wide range of baccalaureate and doctoral programs, and include most of the major academic research institutions in the U.S.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research awards are especially for scientists with quantitative backgrounds looking to pursue independent research in the biomedical sciences, and the K18 career enhancement awards support training in the use of stem cells. The characteristics and requirements for most K awards differ significantly by institute. Finally, the NIH Director’s Pioneer Award (NDPA) has recently been established “to identify and fund investigators of exceptionally creative abilities and diligence, for a sufficient term (five years) to allow them to develop and test far-ranging ideas.”8 Those selected to formally apply for the NDPA from those nominated do not submit a formal research plan since it is expected to evolve during the tenure of the grant. Because the specific scientific plan is not a review criterion, recipients are selected on the basis of their potential—including scientific innovation and creativity, motivation and enthusiasm, and potential for scientific leadership. Individuals at all career stages are eligible for the NDPA and “nominations from individuals at early stages of their career who demonstrate independence of their ideas from their mentors are especially encouraged.” While the Pioneer Awards have great potential to encourage risk-taking by a small number of biomedical researchers, they will likely have little effect on more than a handful of new investigators. In particular, it is difficult for new investigators—who, by definition, have little track record—to have already demonstrated significant creativity and independence. Without even a research plan, the selection is largely based on the track records of the applicants and new investigators have little to show, at least as compared to their more senior colleagues. The outcome of the first round illustrates why the NDPA is unlikely to help new investigators: of the nine awardees (out of 1,300 applications)—all are men in their 40s and 50s, most are tenured professors at elite institutions, and seven of the nine already have current NIH grants (Mervis, 2004a). National Science Foundation The National Science Foundation (NSF) administers one program especially targeted to those at the beginning of their careers. The Faculty Early Career Development (CAREER) Program, offered across NSF, targets those who plan to integrate research and education activities. CAREER awards provide at least $100,000 a year for 5 years to investigators in their first faculty positions. Recipients must be in tenure-track positions, but not yet have received tenure. The application requires an endorsement 8   http://nihroadmap.nih.gov/highrisk/initiatives/pioneer/

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research from the department head and a career-developmental plan from the applicant that describes research and educational goals, the relevance to the applicant’s own career goals, and a summary of prior research and educational accomplishments. Several of the most meritorious CAREER recipients are selected for the Presidential Early Career Awards for Scientists and Engineers (PECASE), although this designation does not include any additional award benefits. Twenty-five percent of the biological sciences directorate’s young investigators are funded through CAREER each year, although the success rate is only 16 percent. Overall, in 2003, the NSF funded 24 percent of research grants submitted by all principal investigators, 30 percent of research grants submitted by new principal investigators, and 20 percent of CAREER grant applications across the Foundation, according to Mary Clutter of the Biological Sciences Directorate in her presentation at the committee’s June 16, 2004, public workshop. NSF does not ask applicants their age, so “new” is defined by the number of years after receiving the PhD. When expressed as a percentage of total awards, awards to new investigators decreased significantly after investigators passed 11 years from PhD. This equates to approximately 40 years old, which is below the median age for receipt of new NIH awards. Because of its broad mission, NSF offers a comparison of biological sciences awards with those in other disciplines. A cross-disciplinary analysis shows the experiences of new investigators in biological sciences are similar to those in mathematics and the physical sciences. Only in computer science and engineering (by a significant margin) and social, behavioral, and economic sciences (by a slim margin) do new investigators have the greatest success in obtaining funding within 5 years after receiving their PhDs. In addition to the CAREER program, NSF fosters independence in a number of ways: Review committees (akin to study sections) are asked to give “extra credit” to beginning investigators. Program officers are encouraged to have balance in their portfolios. As Dr. Clutter described at the workshop, NSF division directors make sure there are “a goodly number of beginners, as well as small institutions, different types of institutions, etc.” The few postdoctoral awards that NSF offers are portable and include automatic starter grants (for approximately $50,000). NSF is concerned about the next generation of scientists and, therefore, places extra emphasis on new investigators. In addition, NSF strives to integrate research and education.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research Other Federal Support for New Investigators In addition to NIH and NSF, the Department of Defense provides another major source of federal funding for new investigators in the biomedical sciences. The Army’s Breast Cancer Research Program offers a physician-scientist training award. This two-phase 5-year award can total up to $700,000. The award is given to MDs or MD/PhDs in their last year of oncology graduate training or in their first 3 years as a junior faculty member. The first, mentored phase of the award provides up to 3 years of salary support and medical school debt relief; the second phase adds direct research support. The Office of Naval Research also administers a Young Investigator Program designed to support the careers of academic scientists and engineers within 5 years of receiving their PhD. It offers up to $100,000 per year for 3 years for salary, graduate student support, supplies, and operating expenses and requires a letter of institutional support. Private Sector Programs for New Investigators A number of programs for new investigators also exist in the private sector, especially at private foundations (see also ACS/BWF/HHMI, 2000). Markey Scholar Awards in the Biological Sciences The Lucille P. Markey Charitable Trust created some of the first career transition awards, known as Markey Scholar Awards in the Biological Sciences. Established in 1983 as a 14-year limited-term trust, the Markey Trust distributed institutional and individual grants, including almost $60 million to 113 Markey Scholars (Lucille P. Markey Charitable Trust, 1996). Academic institutions were invited to nominate young investigators for the awards, which provided salary and research support for up to 3 years of postdoctoral training and for the first 5 years of the awardee’s first faculty position. Support for the faculty phase declined in anticipation of the faculty member obtaining replacement funds from other sources. Among the characteristics that proved especially desirable in the Markey Scholars program were the flexibility in the awardees’ use of the money, including no-cost extensions; the long tenure of the award; the resultant ability to focus on research without having to seek additional funding; and the networking opportunities with the other Scholars. The National Academies is engaged in a multi-year study on the outcomes of grants and fellowships awarded by the Markey Charitable Trust in the biomedical sciences between 1982 and 1997. Among the outcomes

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research of interest for fellowship recipients are publications, grants, and independent investigator status. These results will be helpful data in evaluating the success of career transition awards. Burroughs Wellcome Career Awards The Burroughs Wellcome Fund (BWF) offers the Career Award in the Biomedical Sciences,9 based upon the initial structure of the Markey Scholar Awards. The goal of this $500,000, 5-year award is to help postdoctoral scholars obtain faculty positions and achieve research independence. Applicants must have between 1 and 2 years of postdoctoral study and be nominated by their sponsor institutions. BWF requires 1 year of additional postdoctoral training unless, during the application process, the applicant has been offered a faculty position. Eighty percent of the recipient’s time must be devoted to research. The award provides salary and research funding—up to 1 year of postdoctoral support and 4 years of faculty support. An investigator is not restricted from receiving additional awards from other sources. The BWF career awards program is one of the only programs that has had a formal assessment of its success and influence on the career trajectories of its awardees (Pion and Ionescu-Pioggia, 2003). Box 5-1 summarizes the evaluation. BWF provides training to the awardees in areas not generally addressed during postdoctoral training, such as how to manage a laboratory and how to negotiate an academic-industrial collaboration. BWF also collaborates with the Howard Hughes Medical Institute (HHMI) to host the Laboratory Management Course (BWF and HHMI, 2004).10 National Multiple Sclerosis Society Career Transition Fellowships The National Multiple Sclerosis Society awarded its first three Career Transition Fellowships in 2003. These two-phase awards are given to those with 2-4 years of postdoctoral experience who are engaged in multiple-sclerosis-related research; the first phase includes salary and research support in the 2-year mentored postdoctoral phase, followed by $125,000 annually for salary, personnel, research, and indirect costs during the 3-year faculty phase. 9   BWF also offers an interdisciplinary Career Award at the Scientific Interface following a similar model. 10   http://www.hhmi.org/labmanagement

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research American Heart Association Fellow-to-Faculty Awards The American Heart Association offers a career transition awards program for MD and MD/PhD scientists pursuing independent research careers in areas relevant to its mission. Applicants for Fellow-to-Faculty awards may have no more than 5 years of postdoctoral research training and must work with a mentor to develop a plan for the training phase; the applicant also identifies a mentor for the faculty phase of the award. Awardees receive salary and research support during the training phase and salary, project support, and indirect costs during the faculty support phase. Mentors also receive $5,000 in compensation for their efforts. Applicants are expected to devote at least 80 percent of their time to research-and training-related activities. Keck Distinguished Young Scholars in Biomedical Research The W.M. Keck Foundation established the Distinguished Young Scholars in Biomedical Research Program in 1998. Although the program was originally meant to award only 5 years of Scholars, it was extended for another 5 years in 2003. Thirty institutions are invited to nominate promising early-career biomedical scientists who are in the second, third, or fourth year of their first tenure-track position. Awardees receive up to $1 million over 5 years for salary and research support. The review process is said to emphasize innovative ideas and to support “risky” projects for which funding may be hard to otherwise secure. Unlike several other awards for young investigators, the Keck Foundation does not place limits on teaching, administrative, or grant-writing responsibilities of the awardees, as it sees these skills as important for the careers of the Scholars. Packard Foundation Fellowships for Science and Engineering The David and Lucille Packard Foundation invites the presidents of 50 universities to nominate two professors who have held faculty positions for less than 2 years for their Fellowships in Science and Engineering. Nominees should be “unusually creative researchers” undertaking “innovative individual research” in the natural sciences, physical sciences, or engineering, focusing on areas that do not traditionally receive generous funding from other sources. Awardees receive $625,000 over 5 consecutive years and attend annual Packard Fellows meetings.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research Beckman Young Investigator Program The Arnold and Mabel Beckman Foundation established the Beckman Young Investigator Awards in 1991 and has made about 200 awards totaling over $40 million since that time. Awards are normally in the range of $240,000 over a 3-year award tenure. Applicants must be U.S. citizens or permanent residents who are pursuing careers in the chemical or life sciences and have held tenure-track positions for no more than 3 years. According to the Foundation, “Projects should … represent innovative departures in research rather than extensions or expansions of existing programs. Proposed research that cuts across traditional boundaries of scientific disciplines is encouraged.”11 Pew Scholars Program in Biomedical Sciences The Pew Charitable Trusts has given 20 rounds of awards through the Pew Scholars Program in the Biomedical Sciences, to support junior faculty members as they establish independent laboratories. The program encourages awardees to be “more venturesome in their research and future applications for support than would otherwise be likely.” Faculty within the first 3 years of a full-time faculty appointment as assistant professor or independent researcher are eligible to be nominated by their institution. Scholars are awarded $60,000 per year for 4 years to use for personnel, equipment, supplies, and related travel. The amount for the Scholar’s salary is capped at $10,000, and overhead is limited to 8 percent. Scholars are also expected to participate in an annual meeting to present their research and allow for collaboration and exchange with other Pew Scholars. Searle Scholars Program The Kinship Foundation offers the Searle Scholars Program to “support the independent research of exceptional young faculty in the biomedical sciences and chemistry.” Searle Scholar Awards are made to selected academic institutions to support the independent research of outstanding individuals in the first or second year of their first tenure-track assistant professor appointments. Applicants pursuing independent research careers in biochemistry, cell biology, genetics, immunology, neuroscience, pharmacology, or related areas of chemistry, medicine, and the biological sciences can receive one of 15 grants, which offer $80,000 for each of 3 years. 11   http://www.beckman-foundation.com/byiguide2.html

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research McKnight Scholar Awards The McKnight Endowment Fund for Neuroscience offers its McKnight Scholar Awards for scientists in the early stages of their careers on disorders of learning and memory. Applicants should have already completed their doctoral degree and postdoctoral training and be in the first 4 years of establishing an independent laboratory and research career. Up to six scholars are selected each year for up to 3 years of support at $75,000 per year. Funds may be used in any relevant way to support the Scholar’s research program, except for indirect costs. Damon Runyon Scholar Award The Damon Runyon Cancer Research Foundation grants five Scholar Awards each year to support outstanding scientists as independent investigators. Awardees, who must be within the first 3 years of an assistant professorship, must either be former Damon Runyon postdoctoral fellows or be nominated by their institution (if invited to do so). Damon Runyon Scholars receive $100,000 for each of 3 years that may be used for salary, technical support, equipment, or supplies. Scholars must submit a progress report in the first 2 years of the award as well as a one-paragraph summary of their research written for the lay public. The host department and institution must guarantee that 80 percent of the applicant’s time will be devoted to research, with an accounting for the activities that make up the remaining 20 percent of time and effort specified in the application and progress reports. Sloan Research Fellowships The Alfred P. Sloan Foundation has spent nearly $100 million since 1955 to support the early careers of over 3,800 researchers as Sloan Research Fellows. Tenure-track assistant professors within 6 years of receiving their PhD may be nominated by their departments. The 2-year award of $40,000 provides support for the Fellow’s research, including equipment, travel, or trainee support, but may not be used for salary augmentation or indirect costs. The field distribution has been established by the Foundation and currently awards 116 fellowships, including 16 in neuroscience and 12 in computational and evolutionary molecular biology. American Cancer Society Programs The American Cancer Society offers a number of research grants and mentored training and career development grants that support new in-

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research vestigators. In addition to research scholar grants for those in the first several years of independent research careers, several other programs for senior investigators encourage the inclusion of a faculty member at an early-career stage as a co-investigator. Institutional Independent Research Fellowships Several institutions provide highly prestigious and very flexible research fellowships to promising researchers at an early career stage. Most recipients are recent doctoral-degree recipients nominated by their research mentors or other prominent scientists. Awardees generally spend several years in residence at the host institution and receive both salary and research support. The fellowship period therefore allows these new investigators to establish an independent research program free from having to apply for external funding or fulfilling teaching or administrative responsibilities. Many of these programs were developed following the model of others, in an attempt to provide similar experiences at other institutions. The Carnegie Institution of Washington has supported a small number of exceptional early-career scientists as staff associates in its Department of Embryology since 1979. Staff associates are independent junior faculty members who hold non-renewable faculty-level independent appointments for up to 5 years and are appointed in lieu of or just after completing a regular postdoctoral fellowship. Up to four staff associates at a time are provided with their own laboratory space and funding for research equipment, supplies, and usually a technician. Staff associates are considered to be independent PIs and are eligible to apply for external funding, though institutional resources are generally sufficient during the tenure at Carnegie. Although there is no formal association with an established Carnegie laboratory or PI, staff associates are encouraged to attend regular laboratory group meetings in addition to department-wide activities. The small size of the department and the commitment of its members to the program provide a collegial environment in which staff associates receive necessary guidance and mentoring, even without a formal mentoring system. The Whitehead Institute for Biomedical Research accepts nominations of recent PhD, MD, and MD/PhD recipients for the Whitehead Fellows Program from candidates’ research advisors or other distinguished scientists. The handful of fellows in residence at a time are provided with the space and resources to establish an independent laboratory and conduct an independent research program at the Whitehead Institute. Fellows generally receive support for their own salary, one or two technicians, and

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research necessary equipment, supplies, and overhead. A 3-year appointment is initially made at selection with the expectation that it will be extended to 5 years. Fellows have the opportunity to serve as PIs and to take advantage of the facilities and interactions with colleagues at the Whitehead or neighboring Massachusetts Institute of Technology, free from financial constraints and formal teaching responsibilities. The Fellows Program at the University of California, San Francisco (UCSF) has brought in a small number of promising early-career researchers through a 5-year fixed-term award. UCSF Fellows receive office space and a small laboratory, along with salary and a core research grant, and are eligible to serve as PI on external research grants. Fellows may sponsor postdoctoral researchers and co-sponsor graduate students with UCSF faculty. UCSF Fellows are nominated by prominent scientists, generally just after completion of their PhD or after brief postdoctoral periods. UCSF is also considering mechanisms for including physician-scientists in the program. Unlike most of the other models described here, formal mentorship is an important aspect of the program: UCSF Fellows are encouraged to set up a mentoring committee of three senior faculty members to provide guidance on topics including running a laboratory and hiring research personnel. The University of California, Berkeley awards Miller Research Fellowships through The Adolph C. and Mary Sprague Miller Institute for Basic Research in Science to approximately 8-10 promising scientists at the time of—or soon after—receipt of a doctoral degree. Nominations are accepted from former Miller Fellows and Professors, UC-Berkeley science faculty, faculty advisors and department chairs of candidates, and a worldwide panel of experts. Fellows currently receive a stipend of $50,000 per year with an individual research fund of $10,000 for research, equipment, travel, and other expenses. Harvard University selects about 10 “persons of exceptional ability, originality, and resourcefulness” as Junior Fellows in any field of study at an early career stage each year. Selected by the Harvard faculty who serve as Senior Fellows from nominations by previous research mentors, recipients spend 3 years in residence conducting independent research with few strings attached—other than attendance at weekly lunches and dinners. Junior Fellows currently receive a stipend of $55,500, but generally arrange support for research with members of the Harvard faculty or apply for internal research funds (Junior Fellows do not have PI status for applying for external funding). Although the committee found these institutional independent pre-tenure-track fellowships to be beneficial, the committee did not feel that this model could be successfully adopted by the NIH. First, the fully in-

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research dependent positions require very substantial financial investment on the part of the institution,12 usually providing a start-up equipment package to each fellow along with continuing research and salary support, even though the individuals may only stay at the institution for 3-5 years. Only the wealthiest institutions are likely to be able to provide these resources, and even for them there must be a significant internal reason to divert start-up funds from regular faculty to these special programs. In fact, there is some evidence that other institutions that have tried to adopt similar programs have had difficulty maintaining appropriate funding levels as other needs arise. Moreover, external support to establish or support such programs would essentially be institutional block grants. Although training grants may also be considered block grants, they tend to have a well-defined research focus and close oversight by faculty PIs, in addition to being much more modest in budget. The lack of oversight by NIH on such an institution-based program would make such a program unlikely to receive significant federal support. Second, the fully independent fellowship positions often lack the opportunity for direct personal mentorship by a senior scientist with similar research interests that is the major academic benefit of the traditional postdoctoral period. Although it is desirable for scientists to become fully independent as quickly as possible, for many people assuming an independent position with the complete responsibilities of running a laboratory immediately after completing the PhD may be too soon. This emphasizes the importance of such programs having the full support and participation of senior faculty mentors. European Models Finally, it is worth considering awards that support the independence of new investigators in Europe. The German Research Foundation (Deutche Forschungsgemeinschaft) offers several programs for early-career scientists including the Heisenberg Programme for individuals usually under 35 but no older than 39 with 5 years of salary and research support—and the Emmy Noether Programme, which supports training abroad followed by research and salary support in the first German faculty position. The Volkswagen Foundation Lichtenberg Professorships provide support to outstanding scientists for up to 8 years. The goal is to provide young investigators the opportunity to independently pursue new and 12   Estimates from some programs suggest that institutions devote on the order of $1 million over several years for each Fellow, including salary and research support, start-up costs, and necessary overhead and support services.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research interdisciplinary research at an early stage in their careers. Applicants must be within 3 years of receiving their PhD and under age 35 with a proven research and publication record. Institutions must also submit a binding letter describing how the environment and focus of the department is appropriate for the applicant and committing to cost-sharing during the professorship and continuing support after the award’s conclusion. The European Molecular Biology Organization (EMBO) offers the Young Investigator Programme to young scientists in the first 3 years of establishing their own independent laboratory. In addition to €15,000 per year, EMBO provides an opportunity to network with other scientists at the European Molecular Biology Laboratory (EMBL). EMBO Young Investigators choose an EMBL mentor who provides advice on the awardee’s research project and helps promote the mentee to relevant conferences. The French National Institute for Health and Medical Research (INSERM) offers its Avenir Program for the Promotion of Young Researchers to encourage autonomy for promising young biomedical research scientists. Avenir awardees are provided with a fully equipped laboratory within an INSERM facility or French University Hospital. Applicants receive support of up to €60,000 per year for 3 years and, possibly, financial support to host a foreign postdoc or graduate student. Applicants may already hold a permanent research position at INSERM or other French research institute, university, or hospital; those without a permanent position may apply to develop an independent research project at a host institution. Conclusion Few of these model programs for new or early-career investigators have collected data on their outcomes or the successes of their awardees. Conclusions on helpful elements of the awards come from the few programs that have been evaluated and from anecdotal feedback from recipients, program administrators, and other observers. The lack of rigorous feedback on these awards demonstrates the importance of collecting data on awardees—and an appropriate control group—to determine the effect of the award on the careers of those scientists. However, it is difficult to demonstrate a cause-and-effect relationship between the award and career success. For instance, many of the awards go to the same population of researchers, i.e., the same individuals may receive multiple such awards. Did the award help those selected to advance in their career or receive subsequent funding? Or would the individuals selected have been likely to succeed even without the award? These questions are difficult to answer.