Learning the Lab: Part Two

In January 2010 OTW interviewed Dr. Jonathan Barnwell about his year with his research mentor, Dr. Zhongyu Li.  We are back and have an update as the year Drs. Barnwell and Li spent together comes to a close.

The new biomaterial or implant that you use with your patients today began its life as a thought bubble in someone’s head…someone who dared to say, “What if?” That someone was a researcher.

Dr. Jonathan Barnwell, an orthopedic resident at Wake Forest University School of Medicine, was a recipient of a 2009 Resident Clinician Scientist Training Grant from the Orthopaedic Research and Education Foundation. Dr. Barnwell is researching nerve regeneration under Zhongyu Li, M.D., Ph.D., Assistant Professor of Orthopaedic Surgery at Wake Forest University School of Medicine. Dr. Li is Dr. Barnwell’s mentor.

Commenting on his experience over the last several months, Dr. Barnwell states, “During the first half of the year my role was largely one of project management. Lately, however, I’ve had more responsibilities in the grant writing arena. It has completely ‘brought home’ the fact that writing grants is a real determinant of success—no resources, no research. In taking on this new role, Dr. Li was rather ‘hands off, ’ i.e., he stepped back and waited to see what I came up with. He helped me focus my thoughts and ensured that I kept my points succinct.”

Ignorance is bliss…but not if you want to get something done. Dr. Barnwell:

In the past I was blissfully ignorant of budgetary issues. Now I can see, for example, that if you are going through the methods section you must step back and say, ‘OK, this was a good idea but is it feasible from a budgetary standpoint?’ Mine was a small grant, but as grants get larger you must consider salaries, resources equipment, etc.

Illustrating the hazards of ignoring monetary matters, Dr. Barnwell says, “Let’s say you want to measure how fast and at what point Schwann cells proliferate. The easiest way to do this is to eliminate something from the animals’ diets, meaning that you have to plan for X number of animals for X number of days and at X number of points in time. If your budget cannot accommodate these things you may have to change your questions or change your methodology. Whatever you do, remember that you don’t want to have doubt cast on the results. You can tell when researchers try to cut corners. There is always a flashier way to do it and a barebones way; it is important to balance things out and to determine what the threshold is in the literature. For example, using nucleotide analog labels in DNA will make it fluoresce (but is expensive). The other option is to treat the antibodies with a number of chemicals, which is about five times cheaper than the analog route.”

Also to the points of running a realistic project and maintaining one’s reputation, Dr. Barnwell notes, “Even if your idea is simple there are details that can arise which may make the project harder. For example, we found that there are inflammatory cells that arise in the early stages of nerve regeneration. Our goal was to count the cells but we soon found that there were multiple ways to do this. Our initial approach was standard flow cytometry, but then we realized that we may not be able to get a statistically meaningful result."

It was a great lesson: be sure that what you are proposing is doable.

He adds, “You should rely on people in the literature who have gone before you and try to adapt protocols from projects that are similar to yours. But be mindful that there are often subtle differences that can have huge ramifications if you do not take these details into account. In the end, it is your reputation on the line.”

The methodical approach to research is already inherent in the makeup of most doctors, says Dr. Barnwell. “Physicians are accustomed to being consistent. For example, we do history and physical exams the same way with every patient. But in the research arena, it is easy to get in a rush and be excited about your idea. Dr. Li has emphasized the point that while you may think you are ready to answer the research question right away, you must build your case slowly so that it is easier to go from idea to paper. You’re going to have to prove to reviewers that you can answer the question. "

It is important to remember that there are a lot of parties competing for limited funding…and that many people may be asking questions similar to yours. I advise working with other investigators who have been ‘in the game’ longer so as to strengthen your application and bolster your confidence.

Deutsche Fotothek/Wikimedica Commons

He is also a proponent of removing blinders. “If you’re very excited about your approach you may fail to build in contingencies. That is a mistake, however—you should always plan for what you will do if things go wrong. For example, in looking at different biomaterials that might work with nerve regeneration, I had originally allotted three months for the experiments. Then I realized that the more interesting questions may take longer than three months to answer. It turned out to be closer to five months. The lesson: if you’re not sure what the end result will be then you should be ready to adapt your methods.”

While many residents undertake summer research projects, the experience is often an intellectual exercise as opposed to one that feels practical. Dr. Barnwell: “Even if residents get a taste of research during the summer months they are not able to see the broad ramifications of their efforts. You can’t really understand how the research will ultimately benefit the patients. I am fortunate to have been able to do this full year, beginning with a thorough planning process, then animal trials, to be followed by human clinical trials. It has set the stage for the remainder of my career.”

Dr. Zhongyu Li, whose skills and guidance are now imprinted on Dr. Barnwell, states, “We are truly fortunate to have someone like Dr. Barnwell, who is bright, honest, and hard working. He has demonstrated tremendous initiative, works independently, and has learned as much as he can about peripheral nerve injury so that he can address the challenges in this field.”

Shedding light on the unique opportunities available at Wake Forest, Dr. Li notes, “The orthopedic physician scientist program was established 11 years ago by our former chair Gary Poehling, M.D. and our current chair, L. Andrew Koman, M.D. The goal of this unusual program is to identify and nurture future orthopedic surgeons who are interested in academic medicine. Our greatest strength is the support we receive from the basic science and clinical faculty. I am proud that our research residents have been awarded a number of grants and patent applications, including six grants from the Orthopaedic Research and Education Foundation, two grants from the Orthopaedic Trauma Association, and two grants from the Arthroscopy Association of North America.”

Commenting on some of the issues that arise when teaching someone how to become a solid investigator, Dr. Li explains, “Today, few researchers have all the knowledge and resources to develop translational, multidisciplinary research programs. Therefore, it is most productive to work as a team. We teach our physician scientists the importance of establishing collaborations with both basic scientists and clinicians in other laboratories who can design the most effective experimental protocols to approach research questions."

Overall, the fundamental thing is that one must remain focused, especially when experiments are going well. When experiments are not going smoothly, it is important to think, ‘What is wrong with my approach and/or design?’ instead of, ‘Why am I doing this research?”

If handed the megaphone, says Dr. Li, he would want it known that mentorship is invaluable—especially during the early stages of one’s professional career. “We need someone who is knowledgeable and experienced in the research field to give us guidance and support when we are frustrated, and to remind us to stay focused when we are excited.”

Alas, where are these people? “There potentially are many great research mentors in our orthopedic community. However, as practicing surgeons, our effectiveness in mentoring young clinician scientists is often hampered by time constraints and limited research funding. We need more people to step up and guide our future orthopedists to develop their interest in research.”

Dr. Li concludes, “Mentoring orthopedic residents in clinically-relevant research is a tremendous experience that is personally rewarding. The residents are brilliant people with unlimited potential. As mentors, we are privileged to work with these individuals, and to foster and guide their creativity."

The satisfaction that the mentor receives as the residents mature and present their work in publications and at national and international meetings is unmatched. Finally, working with young investigators provides the opportunity to be challenged and invigorated by the residents’ new ideas and approaches to problems.

"Their thought provoking questions stimulate us to explore and more the field forward.”