In 1925, Sinclair Lewis published Arrowsmith (a novel for which he later won a Pulitzer Prize), the story of a young medical researcher. Martin Arrowsmith, the protagonist, served as a role model for scores of medical students intent on devoting their lives to medical science. The portrait of Martin is vivid, owing to Lewis’ skill and to his close collaboration with microbiologist Paul DeKruif. Lewis brought some knowledge of medical practice to the novel, since his father was a physician. De Kruif worked at the Rockefeller University and, after he wrote “The Microbe Hunters,” was summarily dismissed when colleagues took umbrage with how they were characterized in the book. Together, these two writers evidence an exquisite and insightful comprehension of the pressures of both bench and bedside medicine.
Arrowsmith takes young Martin from his small town to medical school, then to solo practice in a rural town, and through a stint in public health. Ultimately, Martin then goes to work with his mentor in a high powered research institute (modeled on the Rockefeller). He develops a “phage” that acts as an antibacterial. He is enlisted to test this development during an outbreak of bubonic plague in the Caribbean. He wants to test the drug within the structure of a clinical trial, but he is pressured to treat everyone despite inadequate proof of efficacy and safety. His wife, due to her own carelessness and his neglect, dies of plague, and Martin questions his methods and goals.
He returns to New York and becomes director of a research institute, marries a wealthy heiress (nice work if you can get it), but chafes under the demands of the job, especially the social demands like courting donors and raising funds. He ultimately abandons the city, and his wife and child, and sets up an isolated lab in the woods in Vermont. The novel ends with Martin devoting himself to bench research freed from the demands and distractions levied by conventional society.
I read Arrowsmith when I was at a critical juncture in my own career. I wanted to work in infectious disease and do large scale clinical trials, following in the footsteps of my favorite professors at UC Berkeley. I am sure that my own experience as subject in a trial influenced the set of my compass. At the age of six, I became part of one of the largest clinical trials ever, a three year study of the Salk polio vaccine. The vaccine proved effective and when the blinding was broken, those of us who received placebo where the first children to receive the newly approved vaccine (three more shots!!), the bountiful gift to our town, a reward to our families for enrolling us in the study.
Just like so many young aspiring medical scientists before me, I made Arrowsmith my idol. His dedication to science, research method, and medicine, to the exclusion of all else, seemed to me to be the pure and true path. My faculty advisor counseled me to go to medical school and to get an MD, rather than a PhD and, as in the Robert Frost poem “The Road Not Taken,” that has made all the difference. At that critical branch in my career path, the road diverged and I was diverted from research and never really returned. Never did bench work, never did large trials.
I recently reread Arrowsmith, and came away with a very different impression of young Martin. What a jerk! He was devoid of social grace and patience. He contributed to the death of his first wife. He abandoned his second wife, child and society. And the idea of a solitary researcher toiling away in a hut in the woods cooking up basic science soup seems rather absurd these days. The themes of the novel still have resonance and relevance: the role of science in society, the devotion to scientific integrity, the inevitable conflict in between career and personal life, the in-fighting at academic and research institutions, and the taint that comes from over-commercialization in the discovery process.
And discovery still can be made by a single researcher with a dedicated, focused vision. Take the example of Dr. John Eng. While working in diabetes research at the Veterans’ Hospital in the Bronx, NY, he became interested in glucagon-like peptides, which stimulate insulin production before digestion starts. After attending a lecture on reptile physiology, he started working on isolating and refining a peptide derived from Gila monster saliva, which acted to enhance insulin secretion, blunting swings in serum glucose. His supervisors at the VAH were not interested in patenting the molecule, nor were they enthusiastic about commercialization of this discovery. Dr. Eng then contacted several major pharmaceutical companies, but none evidenced interest in his discovery. He spent two years and $8000 out of his own pocket to patent the molecule, exendin-4.
In 1996, he presented his work at a meeting of the American Diabetes Association. A physiologist from Amylin Pharmaceuticals was intrigued by the work (and perhaps more so when a scientist from Eli Lilly also evidenced interest), and the company licensed rights to the entity. In 2002, Eli Lilly indeed stepped in to partner with Amylin, and in 2005 exenatide (Byetta) become a first of a new class of drugs, the incretins, for treatment of Type II diabetes. While the final outcome needed the support of both small and large pharma, this drug exists because of the diligence of a single researcher…an Arrowsmith. But unlike Arrowsmith, Dr. Eng says he is a believer in a balanced life.
In an interview (see http://www.closeconcerns.com/interview-johneng-full.php), he discussed the challenges of research:
To me the hard part is finding something new. There are no guarantees to discovery. You explore, you take a certain path and follow up whatever that path brings. In terms of obstacles, the hardest part was doing many things well.
To my endocrine fellows, I ask, “Can you do one thing well?” And they say, “Yes, yes we can do that.”
And then I ask them, “Do you think you can do two things well?” And they say, “Yes, it’s a little harder, but we can do two things well.”
“What about doing three things well?” Meaning research, clinical practice, and family—my life revolves around those areas and I suspect theirs will too. Doing three things well… doing three things well is very difficult. That’s where you have to make choices – without a supportive family, it is nearly impossible.”
My hero is no longer the fictional Dr. Martin Arrowsmith. It is Dr. John Eng.
