I was born and raised in Brooklyn, NY. At 16, I took a special Ford Foundation
examination that enabled me to attend the University of Chicago (U of C) after my
sophomore year at Abraham Lincoln High School. My education at U of C profoundly
shaped my ability to think critically. After earning my M.D. at the U of C School of
Medicine (1957–1961) and completing a medical internship at the New England Center
Hospital (Tufts University), I pursued a Neurology residency under Richard Richter at U
of C (1962–1965).
As a Neurology resident and postdoctoral fellow at U of C (1964–1967), I had the
privilege of training under Rudi Schmid—an awe-inspiring mentor in academic medicine
and an exceptional medical scientist. Rudi’s influence sparked my lifelong passion for
translational medicine. During this period, I elucidated the pathogenic mechanism by
which unconjugated, unbound bilirubin crosses the blood-brain barrier to cause bilirubin
encephalopathy (kernicterus) in jaundiced newborns, particularly in premature infants.
This work became the foundation of my Ph.D. thesis with Ruth Rhines at U of C (1967).
Once the pathogenesis of bilirubin encephalopathy was understood, the medical
community widely adopted albumin infusions and phototherapy as preventive
treatments in neonatal care.
Determined to deepen my understanding of basic science, I joined Eugene P.
Kennedy’s lab at Harvard Medical School as a postdoctoral fellow (1967–1969). Gene
Kennedy—one of Harvard’s most brilliant and formidable scientists—taught me how to
think like a scientist: how to identify key research questions, design definitive
experiments, and most importantly, learn from failure. During this time, I discovered the
carrier-mediated uptake of choline at synapses, solving the long-standing puzzle of how
acetylcholine is resynthesized after its release from nerve terminals. This insight proved
crucial to understanding cholinergic synapse function, with significant implications for
neurological and neuromuscular disorders.
In 1969, I was recruited to the University of California, San Francisco (UCSF) by Robert
Fishman and Melvin Grumbach, with a joint appointment in Neurology and Pediatrics.
Both were committed to building world-class departments—and they succeeded. At
UCSF, I extended my work on phototherapy for bilirubin encephalopathy, pioneering an
entirely new approach: photodynamic therapy for malignant tumors. We utilized
hematoporphyrin—a compound selectively absorbed by cancer cells—as a
photosensitizer to generate singlet oxygen, selectively destroying malignant cells when
exposed to specific wavelengths of light. This groundbreaking work laid the foundation
for modern photodynamic therapy, now widely used across multiple medical disciplines.
Additionally, my lab was the first to describe phosphorylation of the acetylcholine
receptor in situ, marking the first known instance of receptor phosphorylation as a
regulatory mechanism—a concept now recognized as fundamental across diverse
receptor systems.
One of the most exhilarating chapters of my career began in 1980, when I was
appointed founding director of the Ernest Gallo Clinic and Research Center (EGCRC) at
UCSF. The center was established with a singular mission: to develop therapies for
alcoholism and drug addiction. Under my leadership, the Gallo Center made two major
contributions to addiction research. First, we introduced cell biology techniques to
ethanol research, leading to the identification of adenosine A2A receptor cAMP
signaling and its role in regulating neuronal responses to alcohol and other addictive
substances. This breakthrough opened new avenues for pharmacological intervention.
Second, the Gallo Center nurtured a generation of pioneering addiction researchers—
many of whom became leaders in the field. Remarkably, half of the Gallo faculty went
on to serve as presidents of the Research Society on Alcoholism (RSA), the premier
organization in the field.
After 22 years at the EGCRC, I transitioned to industry, joining Cardiovascular
Therapeutics (CVT) as Vice President for Neuroscience in 2005. One of addiction’s
hallmarks is the surge of dopamine in the nucleus accumbens during drug-seeking
behavior, driving abnormal cravings and compulsive use. At CVT, I developed a novel
therapy aimed at restoring dopamine homeostasis—eliminating the pathological
dopamine surges that fuel addiction while preserving normal baseline dopamine levels.
Following CVT’s acquisition by Gilead Sciences in 2009, I became a Senior Advisor,
guiding this therapy through successful Phase I clinical trials by 2014. To further
advance its development, Louis Lange and I co-founded Amygdala Neurosciences in
2015. If successful, this treatment could revolutionize addiction medicine by providing a
pharmacological solution for alcoholism and drug addiction—preventing relapse and
offering hope to millions.
A successful outcome would be a deeply gratifying capstone to my career: translating
decades of scientific discovery into a transformative medical therapy.