Research by academic surgeons

Clinical research 

There are different forms of clinical research, with the simplest being a case report. A case report usually consists of the description of a unique clinical entity, and is intended to be educational in nature. The accumulation of case reports focused on a single entity can define that disease in greater detail and, over time, improve the knowledge of treating physicians and change their approach to that of a clinical problem. Many case reports are simply observations of a phenomenon that may never be reported again. On the other hand, some case reports change clinical practice because of their direct clinical relevance. For example, the application of hypertension to the treatment of cerebrovasospasm after subarachnoid hemorrhage from a ruptured aneurysm stemmed from a report by Kosnick and Hunt [1], who described two patients with that condition in 1976. Hypertension was quickly adopted into routine clinical practice by neurosurgeons and patient care improved.

Clinical research frequently involves technological improvements which often have widespread effects upon the surgical disciplines. For example, the description of bone wax by Horsley in 1892 allowed bleeding from cancellous bone to be controlled easily. Orthopaedic surgery and neurosurgery could not have progressed without this technological development, yet description of that substance occupied a mere quarter page in the British Medical Journal [2].

Other technological advances have resulted from a recognized need for better instruments for operative procedures. Kenneth McKenzie had difficulty using available trephines to open the skull, as they were poorly designed and often dangerous. He solved the problem by a buying brace and bit at a hardware store, sterilized them, and used this carpenter’s tool to perforate the calvarium at the beginning of a craniotomy. The McKenzie perforator and bur remains a back-up instrument today when modern tools fail [3]. Better heart valves, joint prostheses, pacemakers, and other devices have become available through technological developments that resulted from collaboration between industry and clinical surgeons.

Another form of clinical research is the case series. A case series is usually a retrospective study of a subject intending to review past experience, define current state-of-the-art techniques, and recommend future directions. Retrospective case studies have become more complicated in recent years because of requirements for patient confidentiality and increased scrutiny by Institutional Review Boards. Nevertheless, retrospective studies continue to be invaluable to all clinicians.

Prospective clinical series, on the other hand, are far more complicated, time-consuming, and costly than retrospective case studies. They depend upon protocols that are hypothesis-driven. Prospective clinical studies usually require formidable financial support, computer expertise, compulsive data gathering, statistical review, strict adherence to patient privacy, and significant funding. One such study, currently funded by the National Institutes of Health, focuses on the efficacy of aspirin or warfarin for the prevention of stroke. That study alone will consume over $30 million of taxpayers’ money during its 5-year study period.

The beauty of clinical research is that it has direct application to patient care, provided it is focused and carefully planned. The so-called “wet laboratory” is not necessary, but significant financial and technical support is required, particularly for prospective studies.

Basic research 

Basic research is another avenue available to the academic surgeon. This is a natural area to pursue for those who seek answers to fundamental questions that often arise at the bedside. A core element of postgraduate and postdoctoral research training, basic research hinges upon the scientific method, which must be learned. Many surgeons simply do not have the time or inclination to pursue research training in addition to lengthy surgical training. Nevertheless, the scientific method is the key to successful basic research. It involves the formulation of a hypothesis, developing the methodologies to test that hypothesis, assembling the necessary equipment, performing the experiment, accumulating and analyzing the data, and publishing the results.

Essentials for the first effort in basic research 

Research is a learned skill for most investigators. Rarely have successful investigators been able to become independent and productive without mentoring. Much more commonly, the beginning investigator requires a teacher who has devoted his or her career to training others in the methods of research. Sometimes the mentor is a noted scientist, at other times it may simply be an unsung faculty member in the medical center that likes to teach as well as do research. The mentor becomes an advisor, confidant, supporter, and cheerleader for the young research trainee.

Basic research can go nowhere without protected time to perform the necessary work. Thus, surgery training programs that have no protected time for research will likely produce no research investigators. The environment is not conducive to research commitments. On the other hand, training programs that require research during the training years are highly likely to produce some graduates who are committed to a research career and who will, through their efforts in the laboratory, change the course of clinical practice. Additionally, protected time needs to be adequate time which, in most instances, means at least 1 year, preferrably more.

It is impossible to perform research that meets today’s standards in inadequate and ill-equipped space. The days of “scrounging” for equipment and space are over. The laboratory must be guided by a mentor who has adequate time to teach in a well-equipped laboratory, thus creating a favorable research environment. When this infrastructure is available, then research questions can be asked with a reasonable expectation that they will be answered.

With the infrastructure in place, the mentor and the trainee formulate the hypothesis. This is usually based upon a simple question derived from exposure to an unsolved problem at the bedside. For example, why does breathing stop when intracranial pressure is elevated? That simple question led Harvey Cushing, a pioneer neurosurgeon of the last century, to investigate the problem with his primary mentor, Hugo Kronecker, noted Swiss physiologist of the time. Understanding the so-called “Cushing reflex” followed [4]. This is a phenomenon seen in patients with severely raised intracranial pressure that causes the heart rate to fall, blood pressure to rise, and respiration to cease. Progressive ischemia in the brain stem develops, triggering a systemic sympathetic storm ending in apnea. A simple question asked at bedside can usually be turned into a hypothesis that can be tested. Thus, the need for a well-equipped laboratory, a mentor who understands the complexities of hypothesis testing, and the likelihood that the hypothesis can be proven or disproven become well defined.

The next step involves assembling the equipment necessary to do the experiments, along with learning the techniques required, including animal husbandry, data analysis, drafting the paper, polishing it, and publishing the results. At the beginning, the novice investigator needs to learn all the details of the experiment. A technician is probably not advisable at this early stage because the investigator needs to experience the frustrations as well as the successes of each individual experiment. The results of the project must be published or the project will, in effect, never have been done. Hence, it is the obligation of the mentor and his or her trainee to see the project through to its endpoint. A poorly planned project, without the infrastructure described previously, dooms the project to failure and confirms the suspicion of the trainee that research is not worth the time.

Essentials for the next effort 

Assuming that the first effort was a positive experience, the hypothesis was tested satisfactorily, and a publication resulted from it, the trainee is ready for the next effort. For some, the first effort is the last despite a satisfying experience, as they lack the necessary commitment. For those who coped with failure successfully, enjoyed the thrill of seeing their first hypothesis-driven investigation in print, and who choose to continue their research endeavor, the next effort is similar to the first. The only real difference is that the trainee is older, wiser, more experienced, and probably knows how to address a question better. The infrastructure is intact and pilot data may exist from earlier experiments. A research track record is beginning to accumulate.

Still, the trainee is far from being an independent investigator and continued mentoring is vital to success. The road to independence requires financial support as well as good science. Good mentors are usually supported by extramural grants testifying to their research expertise. Therefore, funding processes and grant writing are also introduced as part of the second effort.

There are many sources of extramural funding for basic research; in fact, there are so many that it is difficult to know where to begin initially. Here again, mentoring becomes an essential. Applying for funding for an adequate time frame, budgeting appropriately for the next experiment, polishing the hypothesis, firming up space and equipment, writing the proposal for expert reviewers, reviewing past accomplishments by the trainee and mentor, describing the relevance of the project to patient care, and meeting submission deadlines are all part of the grant writing process. Most successful investigators find grant writing to be at least as demanding as writing for highly critical and widely read scientific journals, always keeping in mind that grant reviewers are experts in their field with much more sophistication than the average reader of a scientific journal.

Essentials for basic research later on 

Collaborations naturally take place as the trainee grows in his or her expertise. This is particularly true when extramural funding supports the research. Keeping the focus of the project on the clinical problem is vital. The surgeon scientist doesn’t have the opportunity to simply follow his nose, pursuing interesting questions with little relevance to disease processes. Maintaining relevancy to clinical problems is important. As time constraints continue to multiply for the academic surgeon, recruitment and retention of other investigators is essential, since it is nearly impossible to compete for research funding today without collaborators and reliance upon capable research colleagues. Eventually a critical mass of investigators develops consisting of basic researchers, fellows, students, and surgeon/scientists. The research unit then becomes a vibrant, independent, and highly stimulating enterprise.

Reality testing 

Research is an important and attainable “leg” of the three-legged stool in the career of an academic surgeon. Planning, organization, and a collaborative environment are crucial, as few research successes result from luck.

It is important to remember that failure is part of research. Expecting all experiments to be successful is unrealistic. Coping with failure, including rewriting the grant that failed to get funded, is all part of life in science. Despite the frustrations that are inherent in basic research, the rewards can be great, with the satisfaction of a job well done the most obvious reward.

It is also important to remember that major breakthroughs are rare. Occasionally they do occur and diseases such as polio are conquered. More commonly, however, research moves forward bit by bit, often painfully slow at times, but always forward. If there is any doubt about the forward path of research, take a look backward to see where we have come from. Most of us no longer do the same operations we were trained to do years ago—and why not? Because research has changed our discipline and our clinical practice.

When I finished medical school, I did not intend to do research as part of my life in surgery. That all changed when I met a mentor who inspired me during my training days. I had some protected time, assembled space and equipment, developed a hypothesis, and went to it. I’ll never forget my first experiment and publication. Frankly, it was my best.