Surgeon Stars in Scientist Role

Hobart Harris, MD, MPH, leads a double life — maybe even a double, double life if you throw in insignificant moments like eating and sleeping. Yes, he’s a hepatobiliary surgeon (the youngest son of a general practitioner). Yes, he’s a scientist with his own NIH-funded laboratory. And yes, he’s the division chief of General Surgery at UC San Francisco.

Portrait of Hobart Harris
Hobart Harris, MD, MPH

But he also writes screenplays. And while many of us might claim a similar pastime (it is California, after all), how many of us have written, produced and directed our own film? Well, UCSF, it’s time to meet your own version of The Blade, the lead character, created by Harris, in Diary of a Blade, circa 1994.

“My brother, Wendell B. Harris Jr., is a professional actor and writer, and when we were kids growing up [in Flint, Michigan], we were always making movies. Our initial genres were horror and science fiction,” says Harris. Stop-action animation films, shot with an 8-millimeter camera mounted on a tripod, were particular favorites. “We used homemade figurines incorporated with live action, and with very, very rudimentary editing skills,” Harris laughs.

The Harris family later opened a video production studio. Their first independent film, financed by a million dollars in private funds largely raised by Harris and his mother, featured his older brother playing the role of a legendary Detroit impostor. Called Chameleon Street, the film went on to win the Dramatic Grand Jury Prize at the 1990 Sundance Film Festival.

“We were incredibly naïve,” Harris admits. “But we had a self-reliant attitude. We created the opportunity ourselves, rather than waiting for it to happen.”

After the Sundance success, Hollywood called. “We were invited to Hollywood to meet a variety of producers. They wanted to know about our next big idea.”

Was he tempted by the prospect of a film career?

“I looked the film profession square in the eye,” says Harris, “and I realized that I was not of the appropriate temperament to make that my profession. But I also realized that on some level, I would always be engaged with filmmaking, whether that be by writing, producing or directing. I knew, too, that I would do it on my own terms, rather than someone else’s.” And it was in that spirit that the independent film Diary of a Blade, conceived while Harris was a surgery resident at UCSF, was made.

Harris has brought that same single-mindedness to his medical career at UCSF, where — after his initial faculty appointment at San Francisco General Hospital — he assumed his current position on the Parnassus campus.

Who would ever suspect that Harris was once afraid of blood?

“Between my sophomore and junior years in college, I spent a summer at Baylor College of Medicine in a program sponsored by Michael DeBakey. I ended up working on some research projects that required that I perform surgery on animals. I had never done anything like that before and, in fact, when I was growing up, I was deathly afraid of needles and blood. In some ways, this was my test. I found it absolutely captivating,” he says, his voice rising with the memory. “And because it was, I learned to manage my fear.”

The hundreds of patients with biliary, liver and pancreatic diseases who have since been helped by Harris’ steady hands have reason to applaud this personal milestone.

The thousands of Americans who suffer from sepsis — not to mention the 175,000 who die from this overwhelming consequence of infection each year — are also cheering for an equally dramatic breakthrough. That is, if they were well enough to do so. The sad fact is that sepsis is the leading cause of death in intensive care units around the world, killing on average 1,400 people every day.

Harris, a double threat as both surgeon and research scientist, might not have the answer to the problem, but he does have a novel idea. He believes that lipoproteins produced in the liver and small intestine — in addition to carting fat around our bloodstream — play an equally important role in our immune response to infection. And this is critical because inflammation, not infection, is the major cause of sepsis-related tissue damage in the lungs, liver, kidneys and elsewhere.

“The immune-response-to-infection paradigm is that the body has both pro-inflammatory and anti-inflammatory responses,” Harris explains. “It’s a balanced response, like driving a car with one foot on the accelerator and another one on the brake. Sepsis can be seen as an imbalance between the pro- and anti-inflammatory responses of the host.”

The hypothesis that a particular family of lipoproteins (including the famous triglycerides) is part of the regulatory react-and-respond mechanism was, Harris recalls, “essentially unheard-of” two decades ago, when the work began in the laboratory of Harris’ research mentors, Joseph H. Rapp, MD, and John P. Kane, MD, PhD (UCSF professors of surgery and medicine, respectively).

While Harris acknowledges that he continues to toil, in acting terms, off-off-off-Broadway, scientific evidence is mounting in support of his essential idea. He thinks of it as one of “evolution’s biological efficiencies.”

“There are many examples in the body of molecules serving more than one purpose, often executing different functions during different periods of development or under different circumstances. It’s simply more efficient. We think lipoproteins have this dual function, as well, and it is within the context of this evolutionary doubling up — this co-option if you will — that we have made slow but steady progress.”

The elusive goal is simple enough: a lipid-based therapy for sepsis. And while this remains paramount, Harris admits that his creative impulses are now inching him down a parallel path.

“I appreciate the creative opportunities research represents. In surgery, you are in many ways rewarded for performing according to established standards. In research, on the other hand, you are rewarded for being creative, for challenging dogma, for seeking answers. The creativity of clinical medicine is in the interpersonal delivery of care. The creativity in science is in the search for the ever evolving nature of truth.

“One of the hidden secrets of science is the overwhelming influence of serendipity. In the case of lipoproteins as components of the immune system, the more you understand a system, the more chances you have to exploit it. While I still believe there will be lipid-based therapies for sepsis, I also recognize that science leads you in directions you often can’t predict. I am open to the possibilities.”

And he finds himself in the right place. “One of the beauties of UCSF is the incredibly rich intellectual and scientific environment. It has been very easy to form meaningful collaborations with many very talented scientists. From my perspective, UCSF is a scientific candy store.”

For exactly this reason, Harris urges medical students, residents and trainees to don the UCSF coat, experiment with its rare blend of scientific creativity and openness, and sample from the opportunity menu.

“You don’t go to Baskin-Robbins to order vanilla ice cream. You go because it has 31 flavors. You don’t come to UCSF just to become a good doctor, although there’s nothing wrong with that. But at least sample from the menu, even if you walk out with a vanilla cone.”

Harris leans forward and rests his elbows on the desk. From the emotion in his voice to the powerful curl of his fingers, you know that this is no act — and that while he might have traded a prize for surprise, he has still produced a winning life.

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Chameleon Street
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