Q&A WITH Dr. James Rothman ’67

If you had told Dr. James Rothman, back when he was a Pomfret student fascinated by rockets and physics, that he would one day win a Nobel Prize in Physiology or Medicine, he wouldn’t have believed you. However, after his father encouraged him to take a biology course in his final months at Yale, Rothman discovered a new world of research opportunities. He went on to earn his PhD at Harvard Medical School and made groundbreaking discoveries at Stanford University in cell biology, focusing on the molecular machinery responsible for material transfer within cells, which ultimately led to his Nobel Prize. Despite early struggles, Rothman’s competitive drive and support from mentors fueled his success. Today, his curiosity remains strong as he studies neurotransmitter release and synaptopathies, contributing further to the field of science.

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When did you first develop a love for science?
I remember wanting to be a scientist when I was five or six years old. I grew up in an era when the world was launching rockets in the Space Race. I loved building model rockets. I taught myself algebra, trigonometry, and geometry to track my rockets and determine how high they went. Vaccines were also being developed at this time. I was cognizant of the importance of science and technology. It was a value infused in me and many other people my age.

What drew you to the field of biology?
Initially, I wanted to study physics. While at Yale, I was committed to being a theoretical physicist. My dad was a small-town pediatrician and ran a solo practice. He would incessantly say, “You really ought to give biology a chance. Why don't you take a biology course?” In retrospect, I think he believed there were no jobs for physicists, and he wanted me to attend medical school. To make him happy, I took a course in biology, and that was it. Two or three lectures into the course, I began asking research questions that I couldn't ask in physics, and I never looked back. 

You initially went to Harvard Medical School but ultimately switched to their PhD program; what prompted that change? 
I never thought I would practice medicine. I went to medical school with the idea that I would learn the science I needed to be a researcher. Having had a deep education in the physical and mathematical sciences, I missed out on my opportunity as an undergraduate to learn biology. I thought the best thing to do was to get an education in human biology, learn about human diseases, and then see what happened afterward with an open mind.

You began your research and reported achieving little initial success. What motivated you to keep searching?
I was at arguably one of the world's best — if not the best — biochemistry departments at the time. The lab at Stanford was led and founded by Arthur Kornberg, a Nobel laureate who had developed a pioneering understanding of how cells copy their DNA and how they are key elements of cell division on the basis of genetics. He was my hero in the field of biochemistry and a beacon who taught everybody to focus on the long-term value of things. And as successful and prestigious of a lab as it was, it was an environment that allowed me to fail. I had senior colleagues who supported me and my work. There were some times when I started losing confidence, but I gained confidence because the people I really admired had confidence in me.

I also had an experience at Harvard where I did not make any progress in the lab for about a year. Despite my years of studying and my passion and dedication to science, I had become disheartened by the lack of results. I went to my first scientific conference as a graduate student and learned that others in the field were working on what I was working on. It lit a fire in me because I did not want them to make the discovery first. That competitive spirit fueled me to knock out five papers in a year and a half. I learned how to think through problems in an effective way. I ended up having a spectacular PhD thesis and was offered my job as a professor at Stanford because of it. 

What was it like to receive the call that you had won the Nobel Prize?
There's nothing quite like somebody calling you at 4:30 in the morning and telling you that you've won a Nobel Prize and then informing you that Swedish Radio will be getting on the phone line and interviewing you in about two minutes. You wake up pretty quickly. It's an experience.

What was the memorable part of Nobel Week?
While the actual Nobel Prize ceremony was amazing, I enjoyed giving the Nobel Lecture. I took it very seriously and spent a couple of months preparing for it. It was an opportunity to reflect on the field and my work. I tried to address both scientists and non-scientists because the event attracted a big audience. There were probably 2,000 people there, and while I always give lectures, it was a little scary. But it was very humbling and rewarding. It was the absolute high point of the experience. 

What are you working on now?
What I am studying right now is really important to me. I wake up excited to study it daily.
To put it into broad terms, my lab of fifteen young scientists from around the world and I are focused on trying to determine the "CPU speed" of the human brain, which is primarily controlled by how fast neurotransmitters pass between neurons. We are studying how neurotransmitters are released at a speed much faster than other bodily processes. We hypothesize that this is due to the proteins in synapses being evolutionarily optimized into crystal-like structures. By uncovering the steps that form these structures, we hope to gain insights that could lead to treatments for neurological and psychiatric disorders.

In addition to your research, you are a professor. What do you lecture on now?
Nowadays, my time spent teaching is limited, but I give the first lecture to the new medical students at Yale. I lecture on why they should be learning basic science in medical school. Since most medical students feel they have studied enough science and want to be doctors, there's a bit of a hill to climb. I feel like it's incumbent on someone in my position to try to help them understand the value of science in the medical profession. Because if you don't consider the physiology and biochemistry of what is going on in your patient, you'll think of the patient as a statistic. 

Is there any end in sight for your research and what you want to study?
I have no plans to retire. I plan to continue as long as I'm sentient and doing useful work. Sometimes, it's hard to know when it is time to retire, but right now, the younger people are choosing to come and work with me. The last honest people in the world are the young people, and in the end, they're the ones who have the most at stake in their decision as to where to get their training. So they're voting with their feet, and if they continue to vote to work with me, I'll try to be there for them.

You were involved in the construction of VISTA. Tell me about that.
I had the opportunity to share my thoughts with Annum Architects on what should be included in the design. I am just floored by what they came up with and seeing their building come to life. With its beautiful design and fluid interior, the building invites you in and broadcasts the key message that science is not just a body of facts and hypotheses but is an organic and dynamic human process.
 

 

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