Renowned physician-scientist returns to Brown to celebrate the school that hooked him on science

Lemley lecture series guest and alumnus Dr. Arthur Horwich discussed how medical school at Brown sparked a passion for basic science and medicine, a combination that has led to discoveries of significance to Alzheimer’s and more.

PROVIDENCE, R.I. [Brown University] — In 1973, classes for Brown University’s newly formed medical school were held in the basement of the Biomedical Center, behind an imposing, windowless metal door — not the most welcoming or comfortable of environments. But for Arthur Horwich, a member of that inaugural cohort of aspiring physicians, there was nowhere else he’d rather be.

“We would go through that door every day and receive incredible lectures,” Horwich said. “The basic science faculty and clinical experts from the hospitals brought real medical physiology in the form of problems and patients and really gave us their all.”

“Problems and patients” aptly describes factors that have motivated Horwich ever since. He is a pediatrician and geneticist whose desire to apply clinical science to children’s health has led to groundbreaking discoveries that may one day influence treatment of diseases including Alzheimer’s, Parkinson’s and ALS.

In a return visit to Brown on Wednesday, May 3, Horwich traced his educational path in parallel with the intellectual path that led him to the discoveries for which he is known. He spoke in a room packed with scientists in the Sidney E. Frank Hall for Life Sciences as part of the Lemley Family Leadership Lecture Series, which brings accomplished leaders from a range of fields to campus to engage and inspire the University community.

This semester’s Lemley Lecture was offered in partnership with the Warren Alpert Medical School as part of a celebration of Brown’s 50 years of impact in medical education and research, the contributions of alumni and faculty in Rhode Island and around the world, and the school’s promising future ahead.

Looking back at his 50-year journey from medical school, Horwich shared a range of insights.

“You have to work on something that captures you… and not be afraid to make changes of direction to be doing something you really want to do,” said Horwich, who is a professor of genetics and pediatrics at the Yale School of Medicine.

Horwich is captivated by both basic science and medicine, and has practiced and taught both since graduating from Brown in 1975 as the first valedictorian of the first class of medical students. He has also shifted directions over time, folding and unfolding like the cellular proteins he’s devoted his life to understanding.

Horwich came to Brown in the fall of 1969 and enrolled in the school’s master of medical sciences program. He credits his burgeoning interest in biochemistry to Michael Czech, then a post-doctoral student, now the chair of medical research in the program in molecular medicine at the University of Massachusetts Chan Medical School. Horwich joined Czech in the lab of Brown professor John Fain, where they “burned the candle at both ends” studying the metabolic aspects of brown fat thermogenesis.

“Mike is the guy who hooked me on science,” Horwich said. “He taught me how to think scientifically. He was willing to take the time to really train somebody.”

To Horwich, basic science was tons of fun — he couldn’t get enough of “the day-to-day evolution of understanding the systems, the one-on-one discussions, the hands-on experiments.” When biochemist Christian Anfinsen won the 1972 Nobel Prize in chemistry for research into the properties of enzymes, Horwich, Czech and other classmates spent weeks discussing the research and conceptualizing experiments of their own.

Yet Horwich continued to pursue clinical training through Brown, savoring all of the hospital rotations but leaning increasingly towards pediatric training.

“It was a joyful experience taking care of kids and families,” Horwich said. “Particularly at that point in history where there were a lot of bacterial diseases that were knocking kids out — that were treatable if you recognized the condition early enough and treated it with antibiotics, you saved a child’s life.”

After graduating in 1975, Horwich found himself preoccupied with basic science, so he decided to engage in post-doctoral studies at the Salk Institute.

It’s an exciting time to be a trainee and it’s an exciting time to be a faculty member, however young or old. We’re in a magical time for biology.

Arthur Horwich Professor of genetics and pediatrics at Yale School of Medicine; Brown Class of 1975 M.D. alumnus
Arthur Horwich

In the early 1980s, while caring for babies with a lethal X-linked inherited metabolic condition, Horwich pivoted toward clinical genetics — both for DNA diagnosis and the possibility of DNA-based therapy, but also for the opportunity to delve into the “compartmentation problems” of basic science.

Horwich’s professional story is considered a “bedside-to-bench” tale: As a pediatrician, he tended to patients at the bedside while then homing in on the scientific problems that captivated him in the lab.

Horwich’s research initially focused on protein import into mitochondria and resulted in discovery of a "folding machine" inside mitochondria — a ring-shaped structure that provides essential assistance to protein folding in many cellular compartments. More recently, he has focused on how protein misfolding may contribute to neurodegenerative disease. Many of the scientists in the room on Wednesday were interested to hear exactly how Horwich had made these discoveries, and where they will lead.

For his work on modeling the mechanics of how proteins fold, unfold and misfold, Horwich been honored with numerous awards, including the prestigious Albert Lasker Basic Medical Research Award (with his frequent collaborator, Franz-Ulrich Hartl of the Max Planck Institute of Biochemistry). Horwich received an honorary doctorate in medical science from Brown in 2014 and is a member of the American Academy of Arts and Sciences.

Horwich said he relished the chance to celebrate his roots at Brown — the place that encouraged his interest in science while teaching him how to care for patients. And he’s as enthusiastic and hopeful now as he was during the heady days after graduation.

 “I think we’ve got a bright future,” Horwich said. “I think it’s an exciting time to be a trainee, and it’s an exciting time to be a faculty member, however young or old. We’re in a magical time for biology. We just have to hope that society and everything else can hold together so that we can make people healthy.”