Physician-Scientist Career Paths: An Interview With Kristin Knouse

INTERVIEW BY IVAN DURAN

HHPR Editor Ivan Duran interviewed Kristin Knouse. She completed her M.D.-Ph.D. training at Harvard Medical School and Massachusetts Institute of Technology. Upon graduation, she became a Whitehead Fellow at the Whitehead Institute for Biomedical Research. Her laboratory develops novel tools to investigate and modulate organ injury and repair in mouse models.

Ivan Duran (ID): How and when did you know MD-PhD programs were an excellent fit for you instead of one or the other?

Kristin Knouse (KK): I applied to MD-PhD programs because, at the time, I found myself genuinely interested in both basic science and clinical medicine and envisioned a career in which I could unite these two interests. Growing up, I was always interested in biology and assumed if you liked biology you became a doctor. I wasn’t exposed to research until college but as soon as I got involved in bench science I immediately fell in love with it. I became certain that I wanted to pursue research for at least part if not all of my career. However, I was still sufficiently interested in clinical medicine and the prospect of combining both career paths. Applying to M.D.-Ph.D. programs afforded the flexibility of pursuing a combination of these two careers or either one individually. I decided the advantages of career flexibility and multifaceted training outweighed the cost of additional years of training and therefore applied to M.D.-Ph.D. programs during my senior year of college.

ID: What were the main challenges you faced as an aspiring physician-scientist? How did you overcome them?

KK: Research and medicine are individually intensive careers each populated predominantly by people who pursue one or the other exclusively. The classic physician-scientist paradigm is to find an area of focus in which the research and clinical work synergize such that one can successfully pursue two careers with the same number of hours in a day. That said, it is indisputable that pursuing these two distinct paths inevitably requires some sacrifice to each. For some physician-scientists, the synergy and satisfaction that emerges upon marrying these two career paths is worth this cost. However, as I continued my MD-PhD training I increasingly realized that I am a person who prefers to find the one thing I am most passionate about and pour all of my energy into that. I found basic research to be more stimulating and satisfying than clinical medicine and therefore decided to pursue a career exclusively in research upon graduation.

ID: How do MD-PhD students and graduates choose a clinical-leaning or research-leaning career path?

KK: While biomedical research and clinical medicine share a commitment to understanding and treating human disease, I’ve found these two career paths to be quite different in their practice and their reward. Basic research offers you a freedom to pursue whatever questions and perturbations you find interesting whereas clinical medicine requires you to address specific problems within the confines of what is established as appropriate practice. Basic research offers satisfaction through the generation of knowledge and helping people indirectly through such discoveries. However, science typically progresses at a non-linear and not rapid pace, so this gratification is often delayed. Clinical medicine, on the other hand, offers the reward of directly helping individuals on a daily basis. Some people want to enjoy these two distinct types of approaches and rewards and therefore pursue a career that combines both. For others, they find themselves much more satisfied by one particular system and pursue either research or medicine exclusively. I fell into the latter category. I wanted to ask questions and push boundaries in ways not feasible in the clinical environment. I was also more satisfied by the prospect of benefitting many people indirectly with my research than directly helping a handful of patients.

ID: In a research setting how does additional clinical training complement a PhD? What unique insights does a physician-scientist have that perhaps a physician or a scientist does not?

KK: As a basic scientist, my prior clinical training has provided me the benefit of context, questions, and connections. Research requires an exquisite degree of persistence and focus. However, in this focus it is so easy to lose sight of the big picture—to forget the pathway in which your protein of interest acts, let alone the cell type in which that pathway is active, and the larger scales of tissue and organism beyond that. I find that having clinical training makes it easier for me to step back and gain perspective—to remember the greater context of the problem I am studying and make connections between the molecular, cellular, and organismal scales. I think this ability to step back and move across scales is critical at all steps of the scientific process—from developing good questions to interpreting data and drawing conclusions.

Clinical training also provides an endless source of questions. Human disease is one of biology’s greatest observational experiments. So many fundamental advances in biology were born out of a desire to understand or treat a specific human disease. While we have made great strides in this regard, there are still so many diseases for which the underlying etiology is elusive and even more diseases for which there is no curative therapy. These unmet needs in clinical medicine provide a wealth of important questions to be addressed through basic science research.

Finally, clinical training provided me with a second language and a network of colleagues in the clinical realm. If I am working on a research problem that has a clinical application, it is easy for me to contact colleagues familiar with this disease and communicate with them to gain insight into potential applications and foster collaborations.

ID: Having two different trainings is very helpful in terms of career opportunities. How flexible are physician-scientist career paths? Is there a point of no return once a physician-scientist has chosen a clinical or research career path?

KK: I think one of the greatest parts of M.D.-Ph.D. training is the flexibility it affords one to find his or her ideal balance of the two career paths. One can combine research and medicine in any proportion and this proportion is free to change over time. That said, none of us have an eternity ahead of us. Clinical training can take many years and acquiring research funding requires prior productivity. For that reason, I do think it is well-worth determining as early as possible what sort of balance one wants, especially if one prefers to pursue one path exclusively. This ensures one can complete requisite training and establish themselves in their careers while still in their most energetic and creative years.

ID: To that end, what do you hope to accomplish at your lab?

KK: I strive to create an environment where people can embrace their love for science, do their best science, and become the best scientists they can. Within this environment, I am keen to foster a group of scientists passionate about understanding and modulating organ injury and repair. Our lab seeks to build novel tools to dissect cellular processes in the context of a living organism and employ these tools to achieve molecular explanations as to why some organs in our body can regenerate while others cannot. Ultimately, we hope to leverage this knowledge to confer regenerative capacity to non-renewing tissues in the setting of disease. I abide by the principle that no biological problem is too grand so long as it can be deconstructed into smaller parts, and I aspire to see our research make an impact on human disease in my lifetime.

ID: What advice would you give to women who wish to position themselves as leaders and gain independence early in their careers?

KK: Many studies show that women tend to underestimate their competency and this contributes to their attrition from science. I definitely suffered from this early on in my training—I was beyond certain about my passion for science but far less certain that I had whatever it took to pursue a career in science. Initially, these hesitations intimidated me from asking questions in seminars, tackling high-risk research problems, advocating for myself, and committing to a research career. I was fortunate to have mentors who recognized my enthusiasm for research and believed in my abilities well before I did. Through these mentors, I realized that passion for your work is in fact the most important criterion for success. I was especially fortunate to have a female PhD advisor, Angelika Amon, who led by example to demonstrate that women were equally competent and deserving members of the research community. To anyone in their training who feels similar doubts, know that if you love what you do, you have what it takes to do what you love. Establish your own values and goals and don't allow external pressure to compromise them. The road is not always easy, and at times it is quite isolating. Make an effort to surround yourself with a core group of good friends and mentors who support and inspire you. With their help, you will power yourself through the rough patches and continue on to your desired destination.