Learning the Lab: Research Mentorship – Part One

The scientific method is clear-cut and the path of a researcher is well established…as is the path to becoming a physician. But for most orthopedists, those trails don’t converge. For the aspiring clinician scientist, finding his or her way onto the research path—while retaining the life of a clinician—can be daunting. Fortunately, there is help.

Finding the Right Mentor

One physician entering the world of the clinician scientist is Dr. Jonathan Barnwell, an orthopedic resident at Wake Forest University School of Medicine. A recipient of a 2009 Resident Clinician Scientist Training Grant from the Orthopaedic Research and Education Foundation, Dr. Barnwell is pursuing research on nerve regeneration under the mentorship of Zhongyu Li, M.D., Ph.D., Assistant Professor of Orthopaedic Surgery at Wake Forest University School of Medicine.

Dr. Barnwell: “When I arrived at Wake Forest in 2008, I was rather green in the research arena. Like many orthopedists, I had done a summer research project in which I was given a task, completed it, and that was it. There was no follow-up or real understanding of how it fit into the larger picture. I was dissatisfied with only having this ‘snapshot, ’ and was seeking detailed knowledge about how to take a project from design to analysis to manuscript preparation.”

Enter Dr. Li, a recipient of an OREF Career Development Award in 2006. Dr. Barnwell says, “From the outset Dr. Li’s inquisitiveness and enthusiasm made it clear that he was committed to my development as a physician scientist. He had mentored people in the past, and knew that the process required ongoing communication on both sides. At his suggestion, we meet once a week to discuss the status of grants and manuscripts, something that encourages me to stay organized as there is always an upcoming progress report or submission deadline.”

You want a mentor, says Dr. Barnwell, who is inherently excited by the research process, and revels in passing on his or her skills to the next generation of clinician scientists.

It is clear that Dr. Li is engaged in research for reasons more than accumulating grants and scientific articles; he has a persistent energy surrounding research questions, emails me related materials throughout the week, and is always open to my ideas. He loves the process.

This is a case where “been there, done that” is a positive thing. Dr. Barnwell advises, “You should select a mentor who has gone through the research study process many times—you’ll feel much more comfortable taking his or her advice. Additionally, ensure that your mentor is not just interested in the hot topic of the moment, and that this person will pursue the project in a disciplined, methodical manner. The last thing you want is someone who will throw up their hands in frustration if you’re encountering obstacles. Lastly, look for a mentor who understands not just the big picture, but who has solid knowledge of all of the key components, reads the literature and will go to the mat with you if there is a problem.”

Building a Two-Person Team

A mentor can sort of be a backboard with a brain. “Dr. Li lets me bounce ideas off of him, and then gives advice along the lines of, ‘This is a good idea, but go this route instead to capture what you want to look at.’ He helps me veer away from dead ends. For example, I wanted to test the use of a keratin-based biomaterial derived from hair as a treatment for peripheral nerve injury. However, I was having a dilemma with narrowing down the most appropriate measures to assess the true effect of this material on nerve regeneration. Dr. Li said that while it may be valuable to examine the spinal cord as well, it had already been shown that motor neuron survival did not play a major role in what we were studying. Instead, he helped me hone in on the outcome measures that were most indicative of successful regeneration.”

“His input made me confront and reformulate my hypothesis. It’s one thing to say, ‘This growth factor promotes nerve regeneration, ’ and another to be forced to think about how the process is going to occur.”

Providing a bit of background, Dr. Barnwell notes, “We had three goals in our animal study: first, examine nerve regeneration using a growth factor (glial derived neurotrophic factor in combination with the keratin based hydrogel). Specifically, we set out to learn if the factor stayed in or released in the first couple of days. Secondly, we wanted to know how the growth factor and biomaterial cause individual cells to behave (do they migrate more, grow more, etc.). Lastly, we wanted to look at how the animal recovered, and what kind of functional regeneration it would have.”

Dr. Barnwell had ideas…Dr. Li had other ideas. “I was headed in the direction of counting axons and taking histologic measures, but Dr. Li pushed me to do something more functional. He wanted me to pinpoint exactly how what we were doing was affecting the animal, i.e., ‘Is it making a difference?’ and ‘Is the animal able to recover?’ He sent me in a more practical direction, and had me think about the concrete details of the end result I was trying to achieve.”

And if their paths diverge greatly? “Our opinions are not always in sync, of course. For example, when we were looking at ways to analyze cells in culture, we initially didn’t see eye to eye. But Dr. Li understood that I had more recent experience with cell cultures, and let me take the lead in this area. In the end, the science wins. If I approach him with an idea and he is hesitant, that’s one thing; it is much better if I come prepared with evidence, and say, ‘This is what I think and why.’”

Moving Beyond the Textbook

In the formal world of research, animal participation injects a few quirks into the equation. “There are many idiosyncrasies to animal work, ” states Dr. Barnwell. “From getting animal protocol approval to the actual behavior of the animal, it can be unusual sometimes. Dr. Li was has been especially helpful in directing me towards techniques with maximum clinical relevance. Although one of the advantages of working with animal models is standardization and reproducibility, there is still room for variability if one proceeds solely from the scientific literature. Having an expert in the field of peripheral nerve repair as my scientific mentor has allowed me to quickly address seemingly minor methodologic questions such as how many segments of nerve are clinically appropriate for a proper cable repair, and enabled me to focus on the larger scientific picture.”

That big picture can get quite cloudy if you do not approach it with diligence. “At one point Dr. Li helped me with complicated brachial plexus repairs; it was invaluable to have someone able to come into the lab and work one-on-one with me on the operative microscope. I don’t want to go six months into a study and then realize that I didn’t understand the technical nuances involved (putting too much tension on the nerve, not putting the sutures close enough, etc.). There is no way you can get this type of information from reading a manuscript or a textbook.”

Sometimes the best use of the textbook is to prop up a cage…freeing one to think. “Dr. Li’s dedication extends beyond technical consultations—he is a hands-on mentor whose advanced training in neuroscience means that he grasps many of the limitations of working with animal models and can easily troubleshoot problems. One recent example is a study of the glenohumeral joint deformity that follows brachial plexus birth palsy and the potential role of botulinum toxin as a therapeutic agent. The animal model, a neonatal rat, posed significant technical difficulties due to its size. Dr. Li was completely willing to get involved; he came to the lab and determined which involved muscles were accessible to address this question.”

This active support helps to instill a sense of confidence in one’s approach and findings. This in turn frees me to think of more creative solutions to difficult problems and not be so bound by the routes others may have taken.

And what of the freedom from politics? Dr. Barnwell: “I am fortunate to be in an environment that is, for the most part, nurturing of the clinician-scientist. I have yet to encounter a situation where I was influenced to consider certain lines of investigation over others because of reasons beyond the scientific merits. Granted, in scientific research, divergent interests may arise. However, reason most often prevails, and thus, Dr. Li has always encouraged me to make my best case for pursuing questions relevant to our central aim of understanding and enhancing peripheral nerve regeneration. On a related note, he has also been very helpful in directing me to the appropriate administrator. There is no shortage of bureaucracy in academic medical centers and if one is not familiar with the role of certain offices and the necessary protocols, productivity is easily lost.”

Advice for Aspiring Physician-Scientists

When asked about lessons learned, Dr. Barnwell sounds a bit like he’s just emerged from a meditative state. “I have learned—and accepted—that failure is inherent in research. Frankly, a project that proceeds without any surprises or setbacks is often one that did not begin with an interesting question. The critical and often most difficult part is recognizing when and how to pursue alternate routes to answer your original question. Maintaining both persistence and objectivity throughout the course of a project is a skill I will have to hone throughout my career as physician-scientist.”

Proffering a bit of advice to those a step behind him, Dr. Barnwell notes, “The first suggestion I have for next year’s grant recipients is to maintain regular communication with your mentor. When you are the one performing the experiments, there is a tendency to become consumed by managing the day-to-day activities, something that may cause you to lose perspective on where the project is going. Data which I may think is unremarkable may raise important new questions for my mentor.”

The second tip I would offer is that no matter how enticing potential results may seem, there is a heavy price for skipping steps in the scientific process. I have a great deal of respect for my mentor, and so it is only natural for me to want to show him good work. And while characterization and optimization are not always exciting results to show, they are necessary and ultimately will save the mentor and you a great deal of time and resources.

The road of research can be long—make sure that the person beside you is the one you want. No speed dating here…take time to find a thoughtful, experienced mentor who best fits your career interests, goals, and expectations.

Stay tuned for a second article later this year on Dr. Barnwell’s experience.