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The opportunities in basic science for graduating PhD students and for aspiring physician-scientists have never been so extraordinary. The sequencing of the human genome and the development of the human haplotype map have enabled scientists to begin to unravel the basis of complex multigenic disorders. Rapid developments in stem cell biology are impacting many areas of cardiovascular biology and may enable repair of injured myocardium. High-throughput chemical genetic screening, proteomics, and metabolomics are changing the approaches with which investigators characterize novel signal transduction pathways and develop new therapeutic paradigms. Rapidly evolving molecular imaging technologies are non-invasively illuminating the fundamental processes contributing to cardiovascular diseases. New insights into the mechanisms involved in cardiac myocyte hypertrophy and dysfunction have important therapeutic implications for an expanding population of patients with congestive heart failure.
For the young scientist looking to the future, there are major benefits in pursuing a basic science career including the excitement of discovery, the opportunity for life-long learning, and the potential to broadly impact cardiovascular science and medicine. On the other hand, the young investigator considering a basic science career is confronted by many challenges. The budget of the National Institutes of Health has remained essentially unchanged for five years (when considering the impact of inflation). The success rate of R01 grant applications has consistently declined since 2000, and the average age when an investigator receives a first R01 grant (or equivalent) increased to 42.6 in 2007 (NIH Extramural Data Book at report.nih.gov/index.aspx). At the same time, the increased cost of undergraduate and medical school educations have burdened potential young investigators with ever increasing financial commitments. Many academic leaders have suggested that an entire generation of young scientists is “at risk” (www.BrokenPipeline.org). Long hours at the laboratory bench are compensated modestly compared to those of other professions. There is no doubt that embarking upon a career in basic cardiovascular science has significant risks. A frequently asked question—“How do I know whether I will be successful?”—has no certain answers.
This perspective piece focuses on the young investigator or clinician (with a PhD, MD, or both) interested in pursuing post-doctoral training in basic cardiovascular science. It is based in part on the experience of the author, who has been privileged to provide advice to an extraordinary cadre of young scientists pursuing research training, often combined with clinical training, in cardiovascular medicine at the Massachusetts General Hospital. This review will focus on the steps required to secure the ideal post-doctoral fellowship and to initiate research training in a basic science laboratory. Also considered will be the optimal time commitment to research training, as well as the challenges associated with the transition to independence.
Young scientists considering a post-doctoral fellowship in cardiovascular science have varied backgrounds. Most have PhD degrees and substantial scientific training and research experience. The PhD scientist typically undertakes post-doctoral training to gain additional expertise and experience, as well as to garner scientific productivity, before embarking on a career as an independent investigator. Other young scientists embark on postdoctoral training after completing clinical training in internal medicine and cardiology, often as part of a cardiology fellowship program. Many of these MD post-doctoral fellows have only minimal prior scientific training, whereas others received PhDs before or concurrently with MD degrees. Increasingly, cardiovascular science is attracting MD scientists from other fields such as anesthesiology and surgery. Clinically-trained individuals, particularly those without substantial scientific backgrounds, must understand that post-doctoral research training in basic science is substantially different from the training they have completed so far. Moreover, a career combining substantial clinical activities (greater than 20% of effort) with running a basic science research laboratory is extraordinarily difficult. Clearly, post-doctoral training must be tailored to the experience, background, and aspirations of the fellow, but training clinician-investigators and PhD scientists side-by-side enables them to benefit from each others strengths.
When choosing an optimal post-doctoral research training experience, five steps are recommended to successfully identify the best mentor and research program. It is critical to initiate the search for a post-doctoral position at least one year ahead—the best laboratories may have a waiting list!
One of the most challenging tasks for a young scientist is identifying the area of investigation to pursue. The research area should be an important question in cardiovascular biology which offers multiple possible aspects for investigation. A narrowly-focused research question may be answered “prematurely” (before a young scientist has completed training). Reliance on a single assay or technique is too risky as either may be rendered obsolete by technological advances. If the area of interest is too broad, the number of opportunities may be too large to adequately investigate. If the area of interest is too narrow, it may not be possible to identify an optimal training experience. Above all, the young scientist should be passionate about the research area in which they are training. Scientific excitement needs to be a driving force, particularly when incubations are long, assays are repetitive, and positive results are few and far between.
Choosing a research program/laboratory in which to pursue post-doctoral training represents a “career-determining” decision. Senior faculty in the graduate or medical school in which the young scientist has trained often can provide an overview of available opportunities. Thesis advisors and committee members, as well as Residency Program Directors and Division and Department Chairs, are sources of valuable advice. Often these advisors can provide introductions to potential mentors and/or other advisors. The young scientist should seek advice from experts in their chosen field of interest. Not infrequently, it is necessary to gently remind an advisor, who is trying to “sell” his/her own research program, to provide a broad perspective. On the other hand, the best advisors, who provide unbiased and unselfish advice, may also be outstanding mentors.
There is much written about mentorship and the qualities of an outstanding mentor 1–3. The Mentoring Handbook published by the American Heart Association and American Stroke Association (www.americanheart.org/downloadable/heart/1233694796037MentorHbook2e.PDF) is an outstanding resource for trainees and mentors. Lee and colleagues have summarized the key features of an outstanding mentor 2, which include availability, inspiration/optimism, and the ability to provide direction while encouraging creativity. Please see also “Choosing a Research Project and Research Mentor”4 published previously in this series.
Several additional considerations in choosing a mentor deserve mention. First, the optimal mentor for one post-doctoral fellow may not be optimal for another. For example, a fellow without extensive research experience might benefit from working with a less senior, more-available mentor. In contrast, a fellow with a PhD or prior post-doctoral experience may choose to be mentored by a more senior, established scientist and may not require as frequent interactions with the mentor as would a less-experienced trainee.
Second, although many post-doctoral fellows to choose mentors with similar backgrounds to their own, training with a mentor, who has a scientific background different from the trainee, may result in a spectacular post-doctoral fellowship. For example, a young scientist, who obtained PhD training in a lab focused on fundamental aspects of cardiovascular development in Drosophila, may benefit from a post-doctoral fellowship with a mentor who has an MD or MD/PhD and who is focused on translational medicine or cardiovascular physiology. Similarly, a clinically-trained scientist may benefit from a post-doctoral fellowship with a PhD scientist in a basic science department. Often, it is optimal for a trainee to have two or more mentors with complimentary mentoring expertise or experience, but it is critical that one mentor be ultimately responsible for the trainee’s career development.
A third important consideration is the mentor’s track record in the research field of interest to the trainee. Has the mentor been successful in terms of publications and grant support? Information on the grants funded by NIH (including a brief description) is publicly available from the CRISP (Computer Retrieval of Information on Scientific Projects) database (crisp.cit.nih.gov). Information on grants currently funded by the American Heart Association (grant application title only) is available on the AHA website (www.americanheart.org).
A final consideration about choosing a research mentor/research program is that the best basic science training opportunity is frequently located at an institution different from that where the trainee attended graduate school or pursued clinical training.
A critical determinant of success in a post-doctoral training experience is the laboratory environment. The laboratory environment is an important reflection of the mentor, as are the scientists and students recruited to participate in the mentor’s research program. It is strongly recommended that a potential post-doctoral fellow meet with several of the current postdoctoral fellows and graduate students. Ideally, the candidate should sit in on a laboratory meeting. Key questions include:
Having investigated opportunities in a variety of laboratories with a spectrum of mentors, it is highly worthwhile for the young scientist to report back to his/her advisors. The advantages and disadvantages of each opportunity should be reviewed. Experienced advisors can add perspective to a young scientist’s observations.
Many resources are available that offer advice for the young scientist beginning a post-doctoral fellowship including the AHA Mentoring Handbook (cited above), the ScienceCareers website (sciencecareers.sciencemag.org) and a recent perspective piece written by JW Yewdell3.
Having chosen a mentor and research laboratory (and having been accepted), it is optimal for the mentor and trainee to establish a list of shared expectations. This list should include a description of the nature and frequency of the fellow’s interactions with the mentor(s) and the laboratory meetings and journal clubs in which the trainee will participate. Course work should be included in the training plan so as to complement the fellow’s experience and prior training. The list should also include the methods by which the mentor will help the trainee to develop independence (encouraging the fellow to give presentations locally and nationally, teaching the “art” of grant preparation, and teaching how to review a manuscript). The mentor and trainee should agree on a series of anticipated benchmarks by which the mentor and trainee can judge the latter’s progress. It is critical that the mentor and trainee meet on a regular basis to review progress toward achieving these benchmarks and make appropriate course corrections as necessary.
The methods by which a mentor and trainee select a research project vary depending on the mentor and the trainee. For example, a trainee with little prior basic science training (eg. an MD completing clinical training) will need significant direction from the mentor. In contrast, a more experienced scientist (eg. a fellow with a PhD degree) may have a specific line of inquiry in mind and/or may have joined the mentor’s laboratory to learn a specific technology or expertise.
In general, it is desirable to choose a project focused on an important biological question. Often such a project requires collaborations with members of other laboratories. Collaborations enhance scientific programs by bringing together groups of scientists with complementary expertise and resources. Increasingly, multiple research groups are working together to undertake research projects which can not be accomplished by one group or even a few groups. For example, genome-wide association studies (GWAS) often require international collaborations to identify and confirm the association of genomic variants with phenotypes. Ideally, responsibilities for the research work (designing and performing experiments) and the credit (authorships) should be agreed upon in advance, but, in reality, such agreements are not always feasible, in part, because the research work may change as the project progresses.
Although collaborations are a means to enhance productivity during a post-doctoral fellowship, the fellow should also undertake a project in which he/she may take the lead. Ideally, the research project should have achievable short- and long-term goals. There are a number of advantages to completion early in a postdoctoral fellowship of a body of work worthy of presentation at a scientific meeting and publication in a scientific journal. Participation in scientific meetings, both large and small, permits the fellow to learn how to effectively communicate research findings and to network with scientists with shared interests. Publishing a paper early in a post-doctoral fellowship affords the fellow the opportunity to learn or refine scientific writing skills with the guidance of the mentor. An early publication makes it easier to secure extramural funding (see below), and perhaps most importantly, convinces the trainee that the basic science career choice is indeed feasible.
If the goal is to become a leader of a productive and self-renewing research program, a young scientist should plan on at least 3 years of post-doctoral training, and most will require longer. Research training is incredibly demanding. Many scientific disciplines do not lend themselves to a 40 hour, 5 day work week. On the other hand, many post-doctoral fellows are successful without working 80 hours per week. There is no doubt that productivity and success are correlated with the amount of time invested, but the correlation is not perfect.
It is critical to maintain scientific focus, but opportunities to work with colleagues and collaborate generously may enhance scientific productivity (as discussed above). On the other hand, it is important to avoid distractions during post-doctoral training such as writing reviews unrelated to the fellow’s research program. Some “distractions” can not be avoided such as clinical responsibilities mandated by the Accreditation Council for Graduate Medical Education (eg. continuity clinic) or teaching responsibilities required by university departments.
Clinically-trained scientists frequently “moonlight” during post-doctoral research training to supplement their income. Some moonlighting may be unavoidable due to financial constraints associated with medical school loans. It is critical, however, that moonlighting not interfere with research training. Mentors need to monitor trainees for signs of fatigue that can impair learning and productivity, as well as health and safety.
Some clinically-trained fellows attempt to pursue post-doctoral research training concurrently with advanced subspecialty training. With rare exceptions, fellows who undertake simultaneous clinical training and basic science research training do not become successful independent investigators. Clinical leaders (Department and Division Chairs and Clinical Laboratory Directors) need to understand that a sustained, uninterrupted, and protected period of research training time is required to enable a clinically-trained scientist to become an independent investigator in basic cardiovascular science.
There are a multiple mechanisms available to support the training of post-doctoral fellows.5 Sometimes support is available from the mentor’s laboratory/research grants. Often international fellows will come with partial funding from their home institutions. Despite constraints on the overall NIH budget, support for post-doctoral fellows remains a priority. One mechanism by which NIH supports training of post-doctoral fellows is by providing funding for institutional training programs (T32 grants). A list of active NHLBI-supported T32 training programs is provided at apps.nhlbi.nih.gov/trainingt32. In parallel, the NIH also awards individual postdoctoral fellowships (F32 grants). The two programs are similar except that the post-doctoral fellow applies to institutional training programs for T32 support and directly to the NIH for F32 support. In 2007, 30% of the F32 applications to the NHLBI were funded (report.nih.gov/award/success/Success_All_2007.xls). Additional opportunities are available for post-doctoral fellows training at NIH, as well as for fellows from underrepresented racial and ethnic groups and fellows with disabilities. Details are available at www.nhlbi.nih.gov/funding/training/redbook/phdintro.htm. It is important to note that F32 and T32 awards are limited to US citizens and permanent residents.
A variety of foundations provide support for post-doctoral fellowship training. Notably, the American Heart Association Affiliates funded 252 new post-doctoral fellowships in 2007–2008 (www.americanheart.org/downloadable/heart/1202158110957Research%20Facts%202008.pdf). Additional funding sources may be found on a variety of websites including grantsnet.org and www.infoed.org/new_spin/spinmain.asp.
After a period of time in the basic science laboratory sufficient to generate adequate preliminary data and, ideally, to publish a manuscript, a post-doctoral fellow should consider applying for a mentored career development award. These awards generally provide greater salary support than a post-doctoral fellowship award and are of longer duration. Mentored career development awards are designed to enhance the transition from post-doctoral fellow to independent investigator. At NHLBI, two types of mentored career development awards, K08 and K23, are targeted to individuals with clinical doctoral degrees. K23 awards are directed toward patient-oriented research. K08 awards support clinician-scientists training in biomedical and behavioral research, including translational research. In FY 2007, 35% of K08 grant applications to NHLBI were funded (report.nih.gov/award/success/Success_All_2007.xls). NIH institutes, other than NHLBI, provide mentored career development award opportunities (K01 awards) to PhD scientists. NHLBI provides K01 awards to MD or PhD scientists from underrepresented racial and ethnic groups, as well as individuals with disabilities. A new NIH-wide funding mechanism, the K99/R00 award, is designed to provide post-doctoral scientists (either MD or PhD) with both mentored and independent research support. The American Heart Association has a similar program designed to foster the transition of clinically-trained scientists from fellow to faculty: in 2007, 13 new Fellow-to-Faculty Transition Awards were funded.
Applying for research grants is a fundamental part of a career in basic science. Writing a post-doctoral fellowship grant application before joining a research laboratory is an ideal method to become immersed in the scientific topic and to learn where the scientific cutting edge lies. Importantly, establishing research training goals and career development milestones is typically a required component of a post-doctoral fellowship grant application. Writing an application for a career development award or a first independent grant during post-doctoral training enables the fellow to benefit from the grant writing experience of the mentor. Examples of first independent grants include the American Heart Association Scientist Development Grant and Grant-in-Aid. Moreover, the NIH has enacted several new programs to help new investigators to obtain and renew their first R01 grant (grants.nih.gov/grants/new_investigators/resources.htm).
The transition to independence is perhaps the greatest challenge for the post-doctoral fellow and mentor. In some cases, mentors are reluctant to see successful post-doctoral fellows leave the laboratory. In other cases, fellows are reluctant to leave the security of the mentor’s laboratory and confront the risks associated with establishing an independent research program. Difficult questions which must be addressed openly and candidly include: Can the fellow take his/her research project from the mentor’s laboratory? Which career opportunity offers the best chance of long-term success? Again, there are multiple resources with advice for the post-doctoral scientist transitioning to an independent position including the ScienceCareers website (cited above) and the Howard Hughes Medical Institute website (Resources for the Development of Early-Career Scientists, www.hhmi.org/resources/labmanagement/).
In considering whether it is the right time to initiate an independent research program, the post-doctoral fellow should consider several additional questions:
For scientists initiating an independent research program, there are a variety of types of opportunities. Some investigators pursue careers in Medical Centers wherein the faculty appointment and laboratory are based in a clinical division. There is emphasis on teaching medical students, residents, and fellows. For clinically-trained scientists, there is often a clinical commitment, generally 1 to 2 months per year. Other investigators pursue careers in University settings. The investigator’s faculty appointment and laboratory are in a basic science department. Basic science faculty members typically are responsible for teaching undergraduate and graduate students and often medical students. There are many variations in these career settings, with scientists based in Medical Centers playing an active role in teaching undergraduates and graduate students at Universities, and investigators based in University settings contributing to the education of medical students, residents, and fellows.
Many young scientists pursue careers in the pharmaceutical or biotechnology industry after completing post-doctoral training. Although careers in industry typically do not bring academic acclaim, they often offer the rewarding opportunity to focus efforts on the development of new therapeutics. Generally, careers in industry do not require a substantial clinical or teaching commitment.
In summary, a career in basic cardiovascular science offers many benefits and poses an equal number of challenges. To maximize the probability of a successful career in cardiovascular science, it is critical to take the time to identify the right science, the right mentor, and the right laboratory. Having identified the best post-doctoral training experience, the probability of success is correlated with the time and effort put in at the bench. Clearly defined expectations and milestones can facilitate the mentor-trainee relationship and enhance the post-doctoral training experience. The successful transition to independent investigator in basic cardiovascular science offers the promise of life-long learning and discovery, advancing scientific knowledge, and contributing to therapeutic advances.
The author thanks Drs. Donald B. Bloch, Calum MacRae, Randall T. Peterson, and Paul B. Yu for reviewing this manuscript.
The authors acknowledges funding from the NHLBI, which has supported a research training program in cardiovascular science based at the Massachusetts General Hospital for over 30 years (T32 HL007208) and funding from the American Heart Association which has provided generous support for both fellows and faculty in the Department of Anesthesia and Critical Care, the Cardiology Division, and the Cardiovascular Research Center at the Massachusetts General Hospital.
Conflict of Interests Disclosures
The submission date was August 2, 2008.