Maintaining a Vibrant and Productive Laboratory as a Senior Investigator

This issue’s columnist for Paths and Places is Dr James Boyer, the Ensign Professor of Medicine at Yale, former president of the American Association for the Study of Liver Diseases, as well as the International Association for the Study of the Liver, and a senior investigator who runs a vigorous and impactful research program funded by a grant currently in its 40th year. We asked Dr Boyer to discuss his decision to maintain a research program (as opposed to switching his focus to teaching or administration) at this stage of his career. We hope his article, which makes it clear that he has followed his own advice to remain passionate and compellingly interested in research, will be inspiring to investigators at all stages of their careers.

Rebecca G. Wells, MD, AGAF

Associate Editor

Cellular and Molecular Gastroenterology and Hepatology

James L. Boyer, MD

The Editors of Cellular and Molecular Gastroenterology and Hepatology asked if I could provide some perspectives for younger physician scientists on maintaining a productive laboratory over a number of years. I confess that I am quite surprised to realize that this year my R01, currently supported by a National Institutes of Health Merit award, is in its 40th year of continuous funding. I have been enormously grateful to live in a country with the means to provide the support that has allowed me to continue to pursue a career as a physician scientist for all these years. What advice can I give to those of you who wish to do the same, but at a time when our nation is less generous with support, despite greater opportunities to make scientific progress?

Protect Your Time and Your Enthusiasm From the Start

What do I think is the most essential element to a long-term career in research? Clearly, you need to remain passionate about the scientific problem you are studying and compellingly interested in trying to answer new questions as they arise. Without that continued enthusiasm, your interest and commitment will wane and it then is very easy to become distracted by activities that may take you in other directions, particularly administrative activities, Chairmanships, and Editorships. Although these activities are important and of interest in their own right, they cannot help but decrease your time to be creative and productive. Although I did serve as a Section Chief for a number of years, the demands of the job then were less than they are today.

As you begin a career as a physician scientist, your time for independent research needs to be fiercely protected by your Section Chief and Department Chair. This is particularly true during postdoctoral training and your first few years as a junior faculty member. I worry that my junior colleagues are not able to get the protection they so badly need as a result of increasing pressure to supplement their salaries by generating relative value units with more clinical activities. In addition, junior faculty are asked to join committees and study sections and take up other administrative activities earlier than in years past. Fuller Albright¹ cogently warned against these tasks in 1944 in a list of “Do’s and Don’ts” for young investigators presented in his Presidential Address to the American Society For Clinical Investigation and published in the Proceedings of its 36th Annual Meeting, advice that is potentially more appropriate today than when published originally. The more you can avoid diversions while you still are becoming established scientifically, the stronger your base will be for future funding.

Keep Your Thinking and Your Research Approaches Fresh as you Become Established

To have the best chance that your work will be re-funded for continuing grant cycles, you will need to pursue an area of research that meets an unmet medical need and have enough ideas to move the area of your choice forward with novel, rather than me too proposals. Publication of your results is necessary to obtain even initial funding through a National Institutes of Health K08 or K01 award (usually the first applications after postdoctoral training for physicians and PhDs, respectively). You need to put aside sufficient time for grant writing well in advance of the due date and spend a great deal of time on the first page of a grant, outlining your specific aims over and over again until you articulate a compelling and exciting direction. This page is where you must get the attention of and excite the reviewers. If you can limit your specific aims to no more than 3 or 4 at the most, it will help focus your proposal.

Once you get into the body of the research proposal, it is very important to avoid using a new technique unless you provide evidence in the preliminary results that you can actually perform this. I have seen established investigators marked down by a study section for committing this error. Never take your past productivity for granted by assuming that this gives you license to explore uncharted areas without evidence. Just as serious an error, often made by midlevel principal investigators, is continuing to use the same techniques and approaches that they started out with (and often learned during their training). Technical advances are usually what change scientific paradigms and lead to advances in a given field. By keeping at the forefront of new techniques and applying them to the subject of your interests, you will impress review groups that your work will result in new and novel information. Some physician scientists are reluctant to venture into techniques that they are less familiar with, even though this may be just what the project calls for. This usually is solved easily by involving a local expert in this new area in your application as a co-investigator or collaborator. Another alternative is to take advantage of the sabbatical program at your university and spend it in a laboratory, preferably away from your home institution, that can equip you with the new technology you wish to use.

The Challenges of Being at Midcareer

As you progress in an academic career, it becomes increasingly important to surround yourself with younger people who challenge your ideas and begin to contribute in interesting ways to new research ideas and directions. This is one of the most rewarding aspects of becoming a senior investigator. At this time in your career, you also may consider taking on time-consuming activities such as running a departmental section or joining a study section and it will be very important that you have reliable laboratory staff to perform the day-to-day work in the laboratory rather than relying on yourself.

Another important aspect of maintaining productivity is to continue to focus on the long-term goals you have established, but refresh them each grant cycle with new aims and techniques. If you must change the goal of the project, provide a clear and compelling rationale for doing so and state how your prior work has led you in this new direction. Write your application in simple English that is clear and unambiguous, make the figures large enough to be seen easily without a magnifying glass and simple enough to be interpreted easily, and have colleagues review your proposal for clarity of expression, no matter how senior you are. Above all, there is no substitute for publishing your work as much and as often as you can. Book chapters and reviews are occasionally useful, particularly when your work matures to a level that deserves summarizing, but publishing too many dilutes their impact.

Maintaining Your Laboratory as a Senior Investigator

I have been asked why I decided to maintain my laboratory at a time when many of my contemporaries moved on to administrative or teaching jobs and no longer pursued research. In truth, I did consider becoming a Department Chair and looked at several such positions, but about that time, I became increasingly involved with administrative and scientific pursuits at the Mt. Desert Island Biological Laboratory, particularly during the summer months. This activity, which I have pursued annually since 1971, became a very important part of my career both in terms of scientific discovery and in helping a small seasonal laboratory grow to a full-time institution devoted to science and student education. I have gained much satisfaction from these activities and it was clear that they would have needed to be significantly limited had I taken on other major administrative tasks at Yale or elsewhere. Retrospectively, I am grateful not to have done so because it has allowed me to continue with a productive laboratory as well as enjoy the administrative impact that one can have on a smaller institution.

Luck Counts

Finally, there is always a bit of luck involved in maintaining a successful laboratory. Nevertheless, if you maintain your commitment, I do not know of many other careers that are as rewarding as being a physician scientist.