Together, the three men tower as titans in 60 years of studying neurotransmission. Separately, each winner of the 2014 Warren Alpert Foundation Prize said in a scientific symposium that he was humbled by the complexity of the human brain and heartened by the help of colleagues working together to understand the brain’s connections in health and disease.
Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of Johns Hopkins University were honored for their work in neurotransmission—the dialogue among brain cells—and neurodegeneration, when information transfer fails. They share an unrestricted prize of $250,000 and were recognized Oct. 2 at Harvard Medical School.
“The discoveries of these three pioneers have transformed the landscape of neurobiology,” Jeffrey S. Flier, dean of HMS, said in opening remarks at the Joseph B. Martin Conference Center.
“His research has led to the treatment and improvement of the lives of millions of people,” David Ginty, Edward R. and Anne G. Lefler Professor of Neurobiology at HMS, said as he introduced Hornykiewicz.
Reflecting on this discovery, Hornykiewicz said his initial work rested on the simple observation that dopamine levels were low, followed by the “miraculous” replacement of the neurotransmitter with L-dopa.
“I shall never forget how thrilled I was at witnessing the beautiful and simple and logical way in which the observations one by one evolved and fell into place,” he said. “Despite all the still-open questions in Parkinson’s, I’m sure that eventually that concentrated research will lead to a solution.”
After musing on the mysterious nature of what we call the mind, he waved to the audience and said, “I proclaim neuroscience research forever!”
Ginty then introduced Snyder, who developed the first methods for measuring neurotransmitter receptors at the molecular level, as one of the “most creative, imaginative and original thinkers in the biomedical sciences.”
Snyder discovered opiate receptors in the brain, opening up a new era of biochemical analysis that transformed pharmacology’s approach to treatments for depression and schizophrenia.
Echoing Hornykiewicz and his own mentor Julius Axelrod, Snyder said, “Simplicity is the hallmark of a lot of the things I try to do.”
Rather than using physiology to measure the individual receptors and neurotransmitters that make up the synaptic dialogue, he was the first to turn to biochemical methods, leading to his discoveries of such neurotransmitters as nitric oxide and carbon monoxide.
“One theme that I like to convey is that one should not pay too much attention to all the rules of the game. The fun of science is in breaking the rules,” Snyder said about determining how those two neurotransmitters act.
Rachel Wilson, HMS professor of neurobiology, then introduced Roger Nicoll. She cited his groundbreaking contributions to understanding how synapses function, most famously the process thought to be centrally involved in the formation of new memories.
“Roger Nicoll has been the tallest giant among these giants” of neuroscience who were exploring this process, which was controversial at the time, she said. “What I most admire is he has developed a style of experimental design that’s extremely rigorous and that sets a standard for the rest of the field.”
Nicoll has spent his career translating the language of neurons, understanding how repeated synaptic communication—called long-term potentiation—is a form of learning that underlies the capacity to acquire and store information.
“I’ve been studying synapses for a great long time—a little harder to solve than I initially thought,” he said with a wry smile. “The brain is really, really complicated. It just seemed to me the synapse was tractable. Behavior is way too complicated. I leave that to others.”
Nicoll ended his talk by looking back on his career in the lab—and his collaborators.
“To me the most exciting part of science is doing it with someone else and sharing their excitement and frustrations,” he said.
After the prize winners’ reflections, three invited speakers delivered talks and thanked the award winners for their work, on which their own research is grounded.
John Williams, senior scientist at Oregon Health & Science University talked about synaptic transmission that depends on G-protein coupled receptors.
“My hope is to march up and down dendrites and map out the hot spots of dopamine sensitivity,” he said.
Anatol Kreitzer, associate investigator at the Gladstone Institutes at the University of California, San Francisco said that, with all due respect to Nicoll, he does look at behavior as he studies the circuit mechanisms underlying basal ganglia function and dysfunction. Along with electrophysiological and pharmacological methods, he applies optogenetic tools—using light to turn inhibition and activation on and off—to study a list that begins with motivation and learning and ends with mood disorders and neurodegenerative disease.
“The work of these honorees has allowed my research program to be what it is,” Kreitzer said, saluting Hornykiewicz, Snyder and Nicoll.
Beth Stevens, HMS assistant professor of neurology at Boston Children’s Hospital gave the concluding talk, focusing on immune mechanisms of synapse loss in health and disease. She has charted synaptic pruning in the developing brain, showing the role of immune-related molecules in the sculpting of brain connections.
Her more recent work investigates synapse loss in the brains of people before they develop symptoms of Alzheimer’s disease.
“The same immune-related mechanisms that drive synapse elimination in a healthy brain are aberrantly activated to drive synapse loss in disease,” she said. “Can we target microglia to protect synapses against early memory loss?”
This and many other questions remained at the close of the symposium, which Flier summarized as spanning “60 years ago to 60 minutes ago” of neuroscience.
The Warren Alpert Foundation’s scientific advisory board, an international group of biomedical scientists chaired by Flier, is already requesting nominations for the 2015 prize.
The Alpert Prize recognizes scientists whose research has led to the prevention, cure or treatment of human diseases or disorders and constitutes a seminal scientific finding that holds great promise of ultimately changing our understanding of, or ability to, treat disease.
The late Warren Alpert, a philanthropist dedicated to advancing biomedical research, established the prize in 1987. To date, the foundation has awarded more than $3 million to 48 individuals. Seven honorees have also received a Nobel Prize.
