Profiles in surgical research: Dorry L. Segev, MD, PhD, FACS

Editor’s note: The Bulletin is collaborating with the American College of Surgeons (ACS) Surgical Research Committee to present a series titled “Profiles in Surgical Research.” These interviews are published quarterly and highlight prominent surgeon-scientist members of the ACS, with a focus on past recipients of the Jacobson Innovation and Jacobson Promising Investigator Awards.


Dr. SegevThe third interviewee in this series is Dorry L. Segev, MD, PhD, FACS, a transplant surgeon at Johns Hopkins University. Dr. Segev is an internationally recognized expert in the area of organ allocation and has been instrumental in driving transplant policy at the local, regional, and national levels.

Dr. Segev is associate vice-chair for research and director, Epidemiology Research Group in Organ Transplantation, and associate professor of surgery and epidemiology, Johns Hopkins University, Baltimore, MD. He completed his undergraduate degree at Rice University, Houston, TX, and his medical degree at Johns Hopkins. He stayed at Johns Hopkins for both his general surgery residency and abdominal organ transplant fellowship. He has been on faculty at Johns Hopkins since 2006 and pursued a master of health science in biostatistics and a PhD in clinical investigation as a junior faculty member at that institution. He has published more than 250 papers in leading journals, including the Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), and The Lancet. He has received many prestigious awards, including the Jacobson Promising Investigator Award (JPIA) in 2009.

Dr. Segev was interviewed in April 2015 by Juliet Emamaullee, MD, PhD, a transplant surgery fellow at the University of Alberta, Edmonton, and the Resident and Associate Society of the American College of Surgeons representative to the Surgical Research Committee.

Did you always know that you wanted to be a physician?

In high school, I was doing freelance computer programming, and I was writing software programs, including medical office software. However, I did not have much of a connection with the field of medicine. I went to Rice University, where I studied computer science, electrical engineering, and music. I am actually the first person in my family to have completed my undergraduate studies in the U.S. I was born in Israel, and we moved to the U.S. when I was young, when my parents were doing their graduate studies. I am the first physician in my family.

I enrolled at Rice with the intention of being a computer programmer. My focus was software development, algorithms, and artificial intelligence. Computer science is kind of a lonely endeavor. You spend all of your time sitting in front of a computer, struggling with the computer, not really interacting with others.

It was studying music that helped me find that human connection, and it connected me to the Rice student volunteer program. I created a program where we went to the children’s center to present music I was writing to hospitalized children. I enjoyed seeing the relationship between the medical providers and their patients. Having a direct impact on a patient’s life was a very strong draw for me. When the time came to decide what I wanted to do after graduation, I decided to apply to medical school. Fortunately, Hopkins seemed to like “weirdos” like me with unusual backgrounds.

When did you decide on surgery as a specialty?

For me, everything about medical school was new and challenging and interesting. I realized early on that I wanted to become a surgeon because it seemed like the most intense, definitive form of disease management, and it was very hands-on. I had spent hours typing on a computer, and I spent most of my childhood playing the piano, so working with my hands was very natural, and surgical technique came very naturally to me.

How were you introduced to research?

My interest in research started in the basic science lab of Martha A. Zeiger, MD, FACS, an endocrine surgeon at Hopkins who, at the time, was studying microsatellite polymerase chain reaction techniques to improve diagnosis of thyroid tumors. [Dr. Zeiger is professor of surgery, oncology, cellular and molecular medicine; associate vice-chair of surgery development; and associate dean for postdoctoral affairs at Johns Hopkins University School of Medicine.] The thought that we could have a direct impact on patient care through science was very appealing. Through this experience, I started to engage in the duality of coming into work and immediately being able to affect somebody’s life, but then also spending time doing research that could have an effect on patient care, clinical decision making, and policy. The thought that I could combine clinical practice and research as components of the same job was very exciting.

Part of the surgical residency at Hopkins involved spending some time in the lab, so I went up to Massachusetts General Hospital, Boston, and spent three years in the lab of Patricia K. Donahoe, MD, FACS. [Dr. Donahoe is director, pediatric surgery research laboratories, and chief emerita, pediatric surgery service, Massachusetts General Hospital; and Marshall K. Bartles Professor of Surgery, Harvard Medical School, Boston.] At that time, I wanted to be a pediatric surgeon, since I had been so inspired by the children I previously saw as a volunteer. Dr. Donahoe had a very strong, celebrated basic science lab, and I learned in those three years how to ask scientific questions, how to apply for grants, and how to connect the science we were doing to clinical care.

During my fellowship, it occurred to me that I could use all of this quantitative analytical training that I had received as a computer scientist and apply it to the clinical and policy questions we had in transplantation. From there, my interest and passion for outcomes research grew.

It sounds like Dr. Donahoe was an amazing mentor. What impact has mentorship had on your career thus far?

I had several really strong role models for clinician-scientists, including Dr. Zeiger as a medical student, Dr. Donahoe as a resident, and Robert A. Montgomery, MD, PhD, FACS, our division chief, as a fellow. [Dr. Montgomery is the Margery K. and Thomas Pozefsky Endowed Professor in Kidney Transplantation; chief, division of transplantation; and director, comprehensive transplant center, Johns Hopkins Hospital; and professor of surgery, Johns Hopkins University.]

Dr. Zeiger introduced me to science that can impact care, Dr. Donahoe taught me how to think scientifically, and Dr. Montgomery helped me put together the entire picture. He helped me see that I could use the skills I developed as a computer scientist and apply them to important clinical questions. He encouraged me to pursue further formal graduate training in order to really bring something new to our division and our field. We talked about a career for me that would bring a new way of looking at large data sets and mathematical modeling that could connect these ideas into policy and the patient care decisions we make every day. Ultimately, I completed my research training as a faculty member on a National Institutes of Health (NIH) K award. I obtained a master’s degree in biostatistics, which was a very technically demanding pursuit that required a strong background in mathematics, and a PhD in clinical investigation, which taught me epidemiology, study design, and how to work with big data. I also learned how this kind of research can affect policy.

Did anyone think you were crazy to pursue all that additional training, given the time and energy involved?

Absolutely—[and] maybe they still do. Honestly, Dr. Montgomery and my wife were the only ones who didn’t think I was crazy to do it. For everyone else, it was out of the ordinary. First of all, the paradigm was that surgeons who do research do basic science research and have a lab that, if you are lucky, is funded by the NIH. You work on understanding the biology underlying disease processes that you operate on. That was the Holy Grail of surgical research. When I was a resident, outcomes research was something you did in Excel, on your laptop, in the middle of the night while you were waiting for a case. It wasn’t something that people pursued seriously. I don’t think that people in our field were even aware of the power that we have in unleashing these big data or the potential role in driving important policy and clinical paradigms.

To conduct true quality outcomes research, is it necessary to collaborate with someone like you who has a strong mathematical and statistical background? That’s obviously a big asset.

I see a surgeon’s involvement in clinical research manifesting in one of two possibilities. You can “play in the orchestra,” which means you are a collaborative member. You have an important question from the trenches, you are smart enough to understand what is happening in the analytical approach, you have access to the patients, and you collaborate and synergize with people that have the skills to do the research part. But, if you are going to be a “soloist” and really drive the field, then I think you need formal training. Imagine a surgeon who knows the field, knows clinical practice, and also knows the nuances of the analytical tools that are available to us. When you make decisions about study design, you are making them based on a strong knowledge of what’s important and what’s not important. When you interpret variables from a cohort study, registry, or other big data, you understand the clinical nuances of those variables, and you are aware of the different scientific questions involved. You can ask questions that other people might have thought were impossible to answer, or never even thought to ask, because you are aware of these tools and how to use them, as well as their respective strengths and limitations.

Dr. Segev

Dr. Segev multitasking on his treadmill desk in his home office

A lot of clinicians are skeptical of outcomes research because some of what has been published is of lesser quality.

Certainly a lot of lower-quality outcomes research has been published, but the bar is being raised. When you think about studies that have affected national policy and clinical practice, they are published in high-impact journals that are read by physicians in other fields, payors, and policymakers. That research has to be very high quality.

You have been doing research as an independent investigator for nearly a decade. Have you experienced any major obstacles or setbacks along the way?

Every day there is a setback or challenging moment. Trying to balance the life of a surgeon, family member, researcher, teacher, and director of a large group is a daily challenge. The current funding environment is incredibly tough, to the point where you need to be writing 10 to 20 grants a year just to keep a research group above water. So, I spend a great deal of my time writing grants. This process can be interesting but at times incredibly frustrating. One of the most innovative things I helped develop to increase live donor kidney transplantation in this country—kidney exchange—has been developed essentially without NIH funding.

In fact, let’s take it further than that. My colleagues and I laugh at the irony that almost every JAMA, NEJM, and Lancet paper we have ever written has been unfunded, which means the most exciting, innovating, and highest-impact work that I have done has not been fundable, and yet, these are the studies that are changing our field. The projects that are fundable are focused on incremental advances and somewhat “safe,” but the ideas that will shake up our field are not incremental advances. They are aimed at huge paradigm shifts that are nearly impossible to fund, not just because of the priorities of federal funding agencies, but because of the funding timeline of at least two years between writing a grant and getting the money to do the work. Also, it is very disheartening that the current hospital environment judges surgeons based on RVUs [relative value units] and the revenue we generate for the hospital, rather than the quality of the research or our generalizable impact. It is frustrating to see my mentees struggle to find protected time to be successful in their own research endeavors. I would say that every day is a challenge.

With the funding environment the way it is today, are funding agencies being pressured to avoid risks because they have so little money to give? This puts pressure on the investigator to strategically ask for funds. It is such a chess game at some level. Would you agree?

I think that even historically fundable research has always been that which proposes incremental advances. We often say that by the time the grant is funded, you have already completed half the work. If I think of a really exciting idea, and I start designing and doing the study and writing the paper, the paper will likely be published in a high-impact journal long before the grant has even made it through peer review.

During my research training, we were fortunate to have private donor money that we would target toward our most innovative projects. Have you experienced anything similar given the overwhelming success of your program?

I am lucky to have been continuously NIH funded since day one. I personally have three R01 grants that fund my research and a mid-career mentoring grant, which pays a good part of my salary to mentor junior faculty and residents. Certainly philanthropy plays a big role in seeding innovative projects or bridging gaps in funding, but that has not been a major source of funding for me. We have also been fortunate to have funding from the National Kidney Foundation, American Geriatrics Society, American Society of Nephrology, Doris Duke Charitable Foundation, and the American Society of Transplant Surgeons. Sometimes society grants help fund projects that may not be well-suited for federal funding.

How has the JPIA helped you resolve these issues?

For me, this award came right at that tipping point, exactly that point in my career where I had already received some early career development awards, demonstrating that there was promise in the research we were doing and the ideas that I had. However, I had not received a big award yet and was at a point where I was struggling to prove to my institution and my colleagues that the work I was doing had potential. As a result of this award, I was able to convince my institution to keep supporting my time and effort to “shoot for the stars.” I believe that it was a direct result of the JPIA that I was able to do what I needed to do, publish some JAMA/NEMJ papers early in my career, and get the NIH funding that I currently have.

The paired donor exchange program was a monumental breakthrough. What do you consider your biggest accomplishment?

I think my greatest accomplishment has been building the Epidemiology Research Group in Organ Transplantation, which I founded and currently direct. This is a group of unbelievably talented surgeons, physicians, epidemiologists, statisticians, mathematicians, and computer scientists who have dedicated themselves to helping us answer questions in organ transplantation. It has created an environment where we are asking important, potentially high-impact questions on a daily basis.

When I started on the faculty in 2006, this arrangement did not exist at Johns Hopkins or really anywhere else [to my knowledge]. I wanted to not only be answering these questions myself, I wanted a team of people where ideas were flowing freely, and we all held each other to a very high standard of study design and analytical robustness, poised to answer important questions as they came about.

Through this research group, we have been able to pass legislation aimed at improving health care research. We wrote and helped pass the Human Immunodeficiency Virus (HIV) Organ Policy Equity Act, which opens the door for HIV-positive kidneys to be transplanted, and we wrote and helped pass the Charlie W. Norwood Living Organ Donation Act, which made national paired donor kidney exchange possible. We demonstrated and quantified the comparative effectiveness of a protocol by which incompatible patients can undergo transplantation through desensitization, supporting its widespread use, coverage by insurance providers, and acceptance by regulatory agencies. We have also informed and studied various policies in organ allocation in this country. We use what we know from being actively involved in the field of organ transplantation as care providers and surgeons to identify the questions that seem most relevant to our field and our patients and to address these issues using the most appropriate methodology. And we train the next generation of surgeons, physicians, epidemiologists, statisticians, mathematicians, and computer scientists along the way, which is probably the most rewarding part of it all.

It is fortuitous that you are geographically so close to Washington, given the amount of policy work you do.

Yes, it is our proximity to Washington, DC, that got me interested in policy to begin with. As a junior faculty member, I did what is called a “nonresidential policy fellowship,” in which I spent time on Capitol Hill and learned how bills are written and how policy develops in real time. This experience helped me through several congressional policy efforts that we have taken on. We also do a lot of work with the Organ Procurement and Transplantation Network; the field of transplantation is mostly overseen outside of congressional law, so there are a lot of opportunities for people from the transplant community to influence organ allocation and policy decisions in the [U.S].

How have you applied the excellent mentorship you have received to your role as a mentor to other surgical investigators?

I would not be where I am today were it not for the influential and key people that I encountered in medical school, residency, and fellowship. I ended up with a career that somehow evolved to be perfectly suited to my unusual background and clinical interests. It is very different from the vision I had for my future when I was in medical school. These mentors helped me put the pieces together and link my various interests in a way that would help me unite my clinical interests with what I could do to advance the field.

Mentors have a much broader scope of vision than [young physicians] do when we are just entering the field. What I now find most interesting, fun, and gratifying is being able to corrupt (I think some people call it “mentor”) young people in our field. I like to show them why I find transplantation to be so exciting, foster their excitement of learning and moving the field forward, and introduce surgeons to robust epidemiology and statistical methods, as well as introduce statisticians to the field of transplantation.

In my training so far, the best mentors always seem to have an infectious enthusiasm and are truly altruistic—they just want you to be successful without any personal benefit. Have you experienced that?

Definitely, and from both sides, as mentee and mentor. The successes of which I am most proud today involve the accomplishments of my mentees. When I apply for a grant, it gets funded or doesn’t get funded. Of course, I need to get funded so my research group can stay alive, but there is not nearly the same level of excitement that I get when my mentees receive their first career development award, publish their first JAMA paper, or has their first really inspiring success.

What do you think are the greatest challenges facing surgeon-scientists starting their careers now?

For surgeon-scientists endeavoring to develop a serious clinical research career, I think the biggest challenge is finding protected time, resources, and the opportunity for dedicated, focused, formal training. This paradigm has never really existed for clinical research. You finish your residency and fellowship, you get hired to operate, and you take on a big caseload. Years go by, and you lack the opportunity to truly obtain research training. I believe that clinicians need formal training to have the mental tools necessary to perform quality research and subsequently be noticed by their institutions, funding agencies, and everyone else. With formal training, the red carpet seems to be rolled out. Without formal research training, they lack the so-called validity factor, and without that, it can be very hard to get your foot in the door.

What advice would you give trainees who are interested in this career path?

My advice is to find a good mentor, find a supportive environment where there is an opportunity to really focus on research without worrying about generating thousands of RVUs, and to seek formal training at every potential opportunity.

As part of the surgical community, what can we do to facilitate the growth of research?

We need to establish environments where researchers are respected, protected, and nurtured, rather than driven further and further into the culture of generating RVUs.

Have you struggled to find balance between your clinical duties, research activities, and personal life?

One of my greatest challenges has been cutting back on my clinical efforts. As surgeons, we love to operate, we love challenging cases; as transplant surgeons, we love operating in the middle of the night. Forcing myself to reduce the time devoted to clinical care to pursue the formal training that I needed and to increase the protected time that I needed to develop into a scientist was difficult. Now that it has all come together nicely, I feel like I have the balance for me. Today, my career is ideally suited to my passions. I still spend time training residents and fellows in the operating room and providing care to my patients, but I also have enough time and support to accomplish quality research goals.

Dr. Segev

Dr. Segev and his wife Sommer Gentry, PhD, dancing in their home studio

You have so many responsibilities, and yet you have a number of hobbies. How do you find time to do it all?

My wife and I met at the American Lindy Hop Championships as competitors and, subsequently, performed as winners together. We then founded a dance studio in Baltimore. We still teach dance in Baltimore and around the world and greatly enjoy pursuing the “renaissance” interests that we have together. Incidentally, we also collaborate academically, but that’s a story for another day.

We have frequent music parties at our house that we call “house jams” that give me an opportunity to stay connected with playing the piano, guitar, and singing—things I studied before I ever went to medical school. I also try to take time when I travel for academic conferences to stay connected with my camera and my decades-long love for hiking and nature photography. I feel very strongly that nurturing both my scientific/technical side as well as my artistic side has allowed me to remain sane and balanced. I love to corrupt others by introducing them to dance and music and the arts, in the same way that I have enjoyed introducing people to epidemiology, biostatistics, and transplantation.

 

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