Joy in Medicine: Remarks at the Medical College of Wisconsin 2019 Convocation

September 19, 2019

Photo of J. Larry Jameson, MD, PhD

Joy in Medicine

President Raymond, Dean Kerschner, distinguished college officials, trustees, faculty, students, family, and friends, I am honored to speak today at this very special occasion – the 2019 Medical College of Wisconsin Convocation. Thank you for that kind introduction.

As you just heard, I serve as EVP/Dean of Penn Medicine. Our academic medical center includes the first medical school and first hospital in the United States, both founded with a charge from Benjamin Franklin to community leaders. This is a large and impactful enterprise, fulfilling Franklin’s vision and expectations.

That is not where I expected my career to take me!

Each of you will have your own story in medicine. My goal over the next 10 minutes is to highlight decision points in my own career and to emphasize that there is great flexibility and joy in medicine that touches every mission. I have found joy in clinical practice, research, teaching, and mentoring, and will share with you an example of each.

First, how did I end up in Medicine? I had no family members or role models in medicine. Dressed in tie dye T-shirts and bell bottoms in the early 70’s, I came of age in the era of Woodstock. 2001 A Space Odyssey was newly released. It seemed incredibly far in the future, yet 2001 was the average birthday of Penn undergraduates at our recent convocation.

My college interests were eclectic and predominantly in the humanities and social sciences. However, my advisor at the University of North Carolina reminded me of the need to take a natural science course to fulfill degree requirements. I signed up for Introduction to Biology, taught by an outstanding teacher who failed to get tenure the next year, but hooked me on the field for life.

After years of endless debates about symbolism in Edgar Allan Poe, or the existence of the soul, I learned how the DNA double helix, with its complementary strands, created a template for cell replication, and simultaneously created a genetic code that was transcribed into RNA and translated into proteins. I was enthralled by this elegant model of life, captured so clearly in Watson and Crick’s, The Molecular Biology of the Gene.  I still have my notebook with questions in the margins --- For example, “How does this template for cell division relate to the formation of cancer cells?” In short order, and with enormous work, I graduated with a B.S. in Chemistry (physical chemistry included), and in medical school went down the MD, PhD path.

Lesson – follow your curiosity and passion. They are the surest path to joy.

As a newly minted intern at Mass General Hospital, one of my first clinical encounters enlightened me regarding the Joy of Clinical Practice. I was assigned to admit a patient with a diagnosis of metastatic prostate cancer. He had lost weight, was listless and bedridden. My initial assumption was that he was in the final stages of his disease. However, his K+ was elevated. Based upon his history and subsequent laboratory tests, the differential diagnosis included adrenal insufficiency, though this is unlikely unless >90% of the adrenal gland is destroyed by tumor. An ACTH stim test confirmed the diagnosis and cortisol replacement dramatically restored his vitality.

 Lesson – History, Physical exam, Hypothesis, Testing – all lead methodically to the satisfaction of making a diagnosis and improving someone’s quality of life. This is joy in medicine, even if the course of the underlying disease cannot be altered.

Making a discovery also affords joy. I trained in molecular biology and gene transcription. My area of interest involved nuclear receptors that link hormone action to gene expression. A wise mentor encouraged me to connect this basic research to human disease. A candidate disorder involved mutations in the nuclear receptor for thyroid hormone, causing resistance to thyroid hormone action. Over time, we and others identified dozens of naturally occurring mutations. There were two main models for how these mutations caused disease: The favored theory was loss of receptor function, thereby causing resistance. The other model was a selective modification of receptor structure and function such that it acted as an antagonist.

As we mapped more and more mutations, a pattern came into focus, sparing critical receptor domains such as the receptor region involved in DNA binding. We designed a series of experiments to clearly discriminate between these two models. The key experiment was to introduce a second hit mutation into the DNA binding domain, thereby eliminating the potential to act as an antagonist. The result was unequivocal – the mutant receptors were acting as dominant negative antagonists. This changed the field and is a paradigm for other similar mutations.

Lesson – Research is arduous with many failures, and rare successes. But new discoveries bring moments of euphoria and insight, which you can share with collaborators and colleagues through presentations and publications. Moreover, just as we learn from our patients, these naturally occurring genetic disorders teach invaluable lessons. This, too, is joy in medicine!

 As many of you know, a polymerase chain reaction or PCR is a remarkable logarithmic DNA amplification reaction – PCR revolutionized the pace of advances in genetics. I see teaching and mentoring in this framework.  I gained an unanticipated insight into this type of joy when I became an Editor of Harrison’s Principles of Internal Medicine. I had previously edited two very specialized textbooks. I regularly published scientific papers and I was delighted if they were cited 100 times. I soon realized that the impact of the Harrison’s textbook was on a different scale, with several hundred thousand readers worldwide. I began to get very specific questions from readers – doctors from rural Iowa, India, or Argentina. I felt a responsibility to insure that every sentence was accurate, supported by data, and useful in clinical practice. My sense of impact shifted when I realized that perhaps ½ million physicians were basing their management of several thousand patients on the information provided by our authors and editors. This is joy in medicine from indirect impact -- coupled with a large dose of anxiety and humility. Each of you achieve this, in your own way, as you teach students, residents, or nurses; each of these individuals will, in turn, use this transfer of knowledge to manage untold numbers of patients.

Mentoring should be seen in a similar manner. I have benefited from many, many mentors. In one example, for my first formal research talk at a national meeting, a mentor provided feedback after a rehearsal of the presentation, which was allotted 12 minutes. I had compiled many slides, packed with highly technical data, clearly demonstrating my newly acquired prowess in molecular biology. Rather than the applause and praise I anticipated, he thoughtfully and constructively destroyed the presentation, focusing my attention on clarity and the story line.

I am indebted to the late Chester Ridgway for schooling me in how to present scientific work. I have since used his approach with my trainees. A large number of these talented individuals are now Professors at leading institutions such as Harvard, Cambridge, Northwestern, and in institutions throughout the world – in Seoul, Sao Paolo, Tokyo, Melbourne, Paris. I am often surprised when they mention something I said to them, of which I have no clear recollection, but it seemingly changed their trajectory.

Lesson – People are always listening and watching, including the “hidden curriculum.” Ultimately, one’s greatest legacy is comprised of people – how you made them feel, and how you provided them with opportunity. This, too, is joy in medicine!

I will close by looking ahead, not back. I know that medicine has many challenges and is filled with the tragedy of the human condition, and unanticipated events in people’s lives. However, I am convinced that the examples I have cited are enduring features of our profession. Despite the challenges we know too well – EHR, administrative burdens, burnout -- there will always be Joy in Medicine! I find Joy in my current role, overseeing a large institution, which I see to be an ever-evolving ecosystem – each mission being symbiotically dependent on the others.

For example, the discovery of engineered T cells to treat leukemia was based upon rigorous basic research, but totally depended upon access to clinical facilities for manufacturing, highly specialized clinicians to perform the clinical trials, and patients willing to participate in highly novel treatments. Our students learn in this environment and helped to care for some of these patients.

Every generation is amazed to look back at the pace of change in medicine, thinking that it must slow down. But it only accelerates. The 20th Century was an era of physics and moon landings. The 21st Century is an era for biomedicine. This is our time; this is your time. As we help patients and families deal with health challenges that ultimately affect us all, it is important that we celebrate the joy of medicine, which I sincerely hope each of you will experience throughout the next 40 to 50 years of your careers.