Challenges for the MD Physician-Scientist Upon Entering the Lab: From the Grand to the Practical

Abstract

Physicians who seek to become laboratory-based physician-scientists, especially those without a PhD degree, face substantial challenges during the critical transition period between clinical and laboratory training. These challenges range from the complex process of adopting new logic structures and standards of proof to the more mundane but important challenges that accompany extending training in a new discipline when other career options are available. Discussion of these challenges can inform individual and institutional strategies to enhance entry and retention of physicians in the physician-scientist career path.

The idea, and the ideal, of the physician-scientist has a long history in academic medicine. There is an intrinsic logic to the idea. Physicians understand disease through their care of patients and, therefore, are uniquely positioned to understand the limitations of the current state of the clinical art/science. Their understanding of, and frustration with, these limitations can stimulate curiosity and spur the physician to an investigative career, with the long-term goal of increasing understanding of disease mechanisms and ultimately improving therapy. PhD scientists stereotypically do not have direct knowledge of disease through patient care but are skilled in the logical and methodical dissection of biologic mechanisms through controlled experimentation, often in systems that model disease pathogenesis. These 2 worlds, that of the physician and that of the scientist, can meet in the body and mind of the physician-scientist, who has the potential to provide mechanistic insight into clinically relevant disease pathogenesis. However, this unity of purpose should not be confused with a unity of skills: clinical medicine and laboratory science are distinct disciplines with distinct skill sets that must be mastered independently. The degree to which one informs the other, although conceptually logical, is often overstated, to the detriment of trainees.

There are many commentaries and reviews about the importance, training, and support of the physician-scientist [1–6], including some in this volume. I will not attempt to recapitulate these arguments, but will instead focus on what I consider to be the critical transition period during which even the most motivated of physician-scientists can face daunting intellectual and practical obstacles. I focus mainly on the MD physician-scientist who does not have extensive laboratory training or a PhD. Definitions are also important: in this commentary, I define a physician-scientist as an MD or MD-PhD who continues to see patients during his/her entire career and runs a laboratory research program, with a time split of 90:10, research/clinical. I do not mean to imply that physician-scientists directing clinical research programs with a similar 90/10 time split should not be included in the physician-scientist definition, but my remarks are focused on the challenges faced by the physician-scientist pursuing laboratory training.

This target group typically proceeds through clinical training with some interest in laboratory investigation but little sustained experience in the lab. As such, the substantive laboratory training period occurs during subspecialty fellowship, after clinical training is complete. This critical transition point between the completion of clinical training and the beginning of laboratory training holds both great promise and great risk.

THE GRAND

Principle 1

Knowledge of disease through clinical training provides abundant inspiration for investigation, but it does not provide the means for successful investigation.

It is an oft-repeated maxim that physician-scientists are uniquely suited to provide new insights into disease because of their clinical training, and there are abundant examples that support this view. Clinical medicine, especially to the investigatively inclined mind, presents abundant topics for investigation. It is impossible to round on an inpatient infectious diseases service and not immediately realize that the critical problems of antimicrobial resistance, Mycobacterium tuberculosis duration of therapy, and bacterial persistence (to name a few) are ripe for new insights. These problems, for which clinical medicine does not have solutions, can spark a fire in the physician-scientist to seek solutions in the laboratory. This spark may be missing or may ignite a less intense conflagration in a scientist without clinical training. This motivating spark is key to sustaining the physician-scientist as he/she undertakes a completely new training period in the lab. However, a common misperception is that the spark of inspiration is sufficient, rather than just being necessary. The inspiration of clinical medicine does not provide the means to find laboratory-derived answers to clinical problems, only the motivation. The technical skills, endurance, hypothesis testing, and experimental interpretation that are the hallmarks of rigorous laboratory investigation must be acquired within an environment that has a track record of imparting such qualities to junior investigators, rather than one that is explicitly focused on the clinical problem that originally excited the trainee. For this reason, the rigor of the training environment is much more important than the specific topic under study. The budding physician-scientist must choose the highest quality training environment over a burning desire to study a specific topic. If poorly trained, the physician-scientist will never have the skills to answer any question, especially the one that provided original inspiration. It is beyond the scope of this piece to review all of the desirable qualities in a laboratory training environment. However, the MD scientist should seek the highest quality basic scientific training that is available; one that will provide access to the thought processes and techniques that will empower their pursuit of mechanistic answers to clinically oriented questions. Multiple important qualities define a great mentor, but foremost among them and often not discussed, is the willingness of the mentor to foster the trainee’s independence. This willingness, by definition, includes a commitment to allow their trainee to continue their research program as an independent scientist without competition from the mentor. I benefitted tremendously from the generosity of my laboratory mentor, who allowed me to continue my line of investigation in my own lab without competition from him, and I have continued this policy in my own lab. Trainees should feel empowered to ask about this issue when considering prospective lab mentors.

Principle 2

Breadth of knowledge is a valued commodity in clinical medicine. This breadth allows physician-scientists to cross boundaries of disciplines and integrate seemingly diverse fields, but it is also a pitfall in the lab.

Outstanding clinical care, especially in internal medicine, requires a broad fund of knowledge, the ability to integrate new findings into a changing clinical picture, and the willingness and ability to nimbly adjust one’s approach to changing clinical circumstances. In addition, the nature of clinical decision-making necessitates that weighty decisions are made based on incomplete data. Outstanding clinicians weigh probabilities and consequences and make decisions based on inexact data. We hold uncertainty at bay because we know that a decision (in many cases) must be made quickly and can be revised later as clinical circumstances change. Thus, flexibility, boldness, and comfort with uncertainty are some of the key ingredients of masterful clinical management.

Although oversimplified for effect, training in clinical decision-making, as described above, is both a strength and a major pitfall in the laboratory. The boldness of approach and comfort with uncertainty impart a confidence to the budding physician-scientist that allow the trainee to fearlessly forge ahead into his/her new training environment. However, a comfort with making decisions based on incomplete information, and the assumption that such logic can be applied to laboratory experimentation, is the major pitfall that I observe in beginning lab-based physician-scientists. The necessity to act on conclusions based on incomplete information in the clinical arena is imposed by the immediacy of the clinical problem, not by a preference for such decision-making. In the laboratory, the clinical trainee often mistakenly applies this standard of supporting evidence to laboratory experimentation, where it is wholly inappropriate. Thus, the boldness that is valued in the clinical arena becomes a liability; the trainee suddenly appears nonrigorous and unable to muster adequate support for their conclusions. This is a difficult adjustment for many clinicians; they don’t understand why their suspicion that something is right is not taken as adequate proof because the same level of confidence in the clinical arena is sufficient to support monumentally important decisions. The laboratory affords the luxury of time; time to gather supporting data before forming a conclusion. Inability to adapt to the new standards of evidence and time scales of discovery in the laboratory environment underlies much of the frustration, and ultimately the failure, of many clinicians in the lab.

The beginning physician-scientist can adapt to these new standards by immersing herself in the new environment, carefully emulating the scientists in the lab who are trained in scientific reasoning, and recognizing that this new mode of reasoning is not inferior or superior to clinical reasoning but is simply distinct and must be mastered.

THE PRACTICAL

Principle 1

Full and vigorous clinical training enables clinical comfort during the 90:10 phase.

By definition, the physician-scientist training process is one that encompasses training in 2 distinct disciplines, clinical medicine and laboratory science. As discussed herein, this training process is long and introduces a host of lifestyle challenges upon the trainee. The dedicated trainee who seeks to navigate these 2 distinct training programs will always feel pressure to mix their engagement in both worlds, clinical and laboratory. When the physician-scientist becomes a principal investigator (PI), by necessity he/she will be spending the majority of their time managing their research operation, with a minority of time spent seeing patients (ie, the proverbial 90:10 split). Reentering the clinic intermittently can be daunting: clinical skills may atrophy, and formerly readily available knowledge is no longer easily accessible. In this circumstance, the 90:10 physician-scientist succeeds (ie, maintains their clinical comfort and involvement) or fails based on the strength of their clinical training.

In this context, attempts to mix clinical and laboratory training or to facilitate laboratory training by shortening clinical training are misdirected, if our goal is to train physician-scientists who will remain clinically engaged. If our goal is to train laboratory PIs with an MD after their name, then maximizing laboratory experiences during clinical training makes sense. Otherwise, by diluting clinical training, we are enhancing the possibility that the physician-scientist will be uncomfortable when returning to the clinic and will ultimately abandon clinical practice. Each discipline, clinical medicine and laboratory science, requires its own dedicated training period, during which the trainee masters the distinct, but equally difficult, thought processes that govern outstanding clinical care and laboratory investigation. I am sympathetic to the challenges that excessive training length impose upon the trainee and agree that efforts to shorten training are laudable, at least in the abstract. However, shortening clinical training or diluting clinical training with research experiences ultimately is counterproductive and I believe originates from an assumption that research training takes precedence over clinical training. This assumption may originate from the traditional dominance of lab-based physician-scientists in leadership roles in academia, but it is an assumption that I believe must be reexamined. For these reasons, although many may disagree, I do not encourage budding physician-scientists to “short-track.”

Principle 2

Academic prestige and intellectual fulfillment don’t pay the mortgage (or day care).

Especially for the MD trainee without a PhD, entering the laboratory for an extended postdoctoral fellowship at the end of clinical training is challenging on many levels, some of which are outlined above. An often overlooked challenge is the emotional and financial stress that this decision can invoke. Emotionally, it is difficult to go from the height of clinical skill to the uncertainty of learning a completely new skill set. The feeling of incompetence that inevitably overcomes any new laboratory trainee (MD or PhD) with each failed experiment is difficult for anyone, but is especially hard having just mastered clinical medicine through 7+ years of training. Financially, the choice to extend training through a laboratory-based postdoctoral fellowship often coincides with life events such as marriage, starting a family, or home purchase. The choice to continue training is made when much more lucrative clinical careers are readily available, making the choice even more financially stressful. Surveys of the barriers to academic medical careers have repeatedly identified financial factors as important [7]. To encourage trainees to undertake this path, we must support them financially during the critical transition period. It is hard enough for trainees to acquire the necessary skills to be a successful physician-scientist; they should not also need to wonder whether they will have a salary or whether their trainee-level salary will persist for years. The reality that academic medicine must entail a sacrifice of time and lifestyle is still true, but glorifying these sacrifices and not acting to minimize them is unfair to trainees and ultimately counterproductive. Of course, there are multiple programs to provide support to physician-scientists (K08, K23, K99/R00, foundation programs), but these are not sufficient or timed optimally to support all phases of career development. The competitiveness of these awards (in part due to National Institutes of Health funding limitations) limits the MD physician-scientist pool early in the this transition period and may exclude promising trainees who abandon the career path due to lack of support. Institutional support, in the form of internal training programs that can bridge these grant programs, is essential. If a physician-scientist trainee has committed to laboratory training beyond the obligatory fellowship period, and shows some promise, institutions should use philanthropic sources to provide competitive salary support at an attending level while training is continued. It is not enough for institutions to encourage the physician-scientist career path in the abstract; tangible institutional support early in the transition period must be committed if we are to sustain our trainees in this difficult, but ultimately rewarding and beautiful, career path.

Notes

Acknowledgments. This work was supported by P30 CA 008748 from NCI and U19 AI111143 from NIAID.

Supplement sponsorship. This work is part of a supplement supported by the Ragon Institute of MGH, MIT, and the Harvard University Center for AIDS Research P30 AI060354.

Potential conflicts of interest. The author reports no conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References