Paul Greengard, a Nobel Prize-winning neuroscientist who exposed the mechanism by which tens of billions of nerve cells communicate, shining a light on the inner workings of the brain and helping to advance the treatment of neurological and psychiatric disorders, died April 13 at a hospital in Manhattan. He was 93.
His death was announced by the Rockefeller University in New York, where he was director of the Fisher Center for Alzheimer’s Disease Research Foundation and had taught since 1983. He had heart problems, said his wife, German-born sculptor Ursula von Rydingsvard.
Dr. Greengard began his career in the 1950s, at a time when biophysics was a nascent field and neuroscience did not yet exist as a stand-alone discipline. His work was defined by a pivotal early decision to study the chemical underpinnings of nerve cell communication, in an era during which most scientists believed that messages were relayed through electrical means, by the flow of charged ions.
In part through his research, neurons are understood to talk to each other primarily through a chemical process called signal transduction. Dr. Greengard focused on a particular type of transduction, slow synaptic transmission, in which neurotransmitters such as dopamine or serotonin effect changes that can last from a few seconds to several hours, affecting mood, alertness and even sensory perception.
Early on, his research was guided by a hunch: that a mechanism used to store sugar in liver cells could also be crucial to the brain. Through that mechanism, phosphorylation, phosphate groups are added to a protein, changing its function and serving as a kind of biological switch.
He soon learned that it was crucial to slow synaptic transmission, although few of his peers seemed to take notice. “No one was terribly interested — it wasn’t ready for prime time,” Dr. Greengard once told the New York Times. “People said, ‘Poor Paul, I’m sure he’ll find his way back onto the right path.’ ”
Another neuroscientist, Charles F. Stevens at the Salk Institute for Biological Studies, told the Times, “Paul was alone for years, taking an approach that the electrophysiologists didn’t care about.”
Dr. Greengard went on to detail the cascade of chemical processes that take place after dopamine and other neurotransmitters reach a neuron, and in 2000 he shared the Nobel in physiology or medicine with Arvid Carlsson and Eric R. Kandel, for their separate research on the role of signal transduction in the nervous system.
“His discoveries laid out a new paradigm requiring the understanding of the biochemistry of nerve cells rather than simply their electrical activities,” Richard P. Lifton, a biochemist and president of Rockefeller University, said in a statement. “Today, abnormalities in signaling among neurons are recognized to underlie many neurologic and psychiatric disorders including Parkinson’s disease, schizophrenia, depression, attention-deficit/hyperactivity disorder, and substance abuse.”
Dr. Greengard himself studied signaling problems in nerve cells and the role that neurotransmitters play in diseases such as Parkinson’s. His research paved the way for the development of the antidepressant Prozac, which works partly by increasing serotonin levels, and in 2006 he and his colleagues announced they had discovered a protein known as p11, which modulates serotonin and seems to play a key role in depression.
Outside the scientific community, Dr. Greengard was perhaps less known for his Nobel-winning research than for what he did with his Nobel winnings. On the same day his prize was announced, he said he had decided to use his share of the award — about $400,000 — to fund an annual $50,000 prize for female researchers.
“I hoped to bring more attention to the work of brilliant women scientists,” Dr. Greengard told the Times in 2006, citing ongoing bias against women in science. “Perhaps this will bring them further recognition and even a Nobel.”
The award was named in honor of his mother, Pearl Meister Greengard, who died while giving birth to Dr. Greengard. Until he was 20, he had believed his stepmother was his birth mother; he once explained that his Episcopalian stepmother wanted to keep him from knowing that his mother was Jewish.
“I don’t have a single photograph of my mother,” Dr. Greengard said. “When I married, my wife, Ursula, put a picture of a woman we thought was Pearl Meister above our mantelpiece. Ten years later, we discovered this was someone else’s mother. Since there’s not a shred of physical evidence that my mother ever existed, I wanted to do something to make her less abstract.”
Paul Greengard was born in Queens on Dec. 11, 1925. His father was a vaudeville singer, dancer and comedian who later worked in cosmetics; he remarried when Dr. Greengard was 13 months old. His older sister Chris Chase was a journalist and actress who co-starred in Stanley Kubrick’s 1955 film “Killer’s Kiss” under the name Irene Kane; she died in 2013.
Dr. Greengard enlisted in the Navy in 1943 and was dispatched to a research group based out of MIT, where he helped develop a radar system designed to warn against Japanese kamikaze attacks in the Pacific.
After World War II he attended college on the G.I. Bill, receiving a bachelor’s degree in 1948 from Hamilton College in Clinton, N.Y. He had planned to pursue a career in physics but experienced a change of heart after learning that the only graduate fellowship available was funded by the Atomic Energy Commission.
“I thought there were better ways of spending my life than trying to destroy mankind,” he once said.
At the suggestion of his college roommate’s parents, both physicians, he turned to biophysics, studying under Haldan Keffer Hartline (later a Nobel Prize-winner) at Johns Hopkins University. He received a PhD in 1953 and did postdoctoral work in Britain at the University of London, the University of Cambridge and the National Institute for Medical Research.
Dr. Greengard said he considered spending his career in England, which he found “particularly compatible” with his reserved personality at the time. But insufficient funding for scientific research, as well as a dearth of central heating, led him to return to the United States. He directed the biochemistry department at Geigy Research Laboratories and was a pharmacology professor at the Yale School of Medicine before joining Rockefeller.
Although Dr. Greengard was widely admired for his championing of women in science, his reputation was bruised in 2007, when a researcher, Effat Emamian, sued Rockefeller University for discrimination, alleging that Dr. Greengard undermined her scientific research and that she had been fired because she complained about the treatment.
He apologized for being “rude” in their conversations about her research, according to the New York Post, and in 2018 a jury awarded Emamian $2 million in emotional damages, later reduced to $200,000 plus back pay.
Dr. Greengard’s marriage to Carola Hamburger ended in divorce, as did a brief second marriage. He met von Rydingsvard when they were both teaching at Yale, and they married in 1985. In addition to his wife, survivors include two sons from his first marriage, Claude Greengard and Leslie Greengard; a stepdaughter he adopted, also named Ursula von Rydingsvard; a sister; and six grandchildren.
After winning the Nobel Prize, Dr. Greengard seemed to maintain the same output as he had before, continuing his research into Alzheimer’s, Parkinson’s and antidepressants. It was not, he joked, that he was a “genetic freak” capable of maintaining a world-class output into his 80s. Rather, the nature of scientific research had changed; he was leading a collaborative team of nearly 60 people, not bounding into the unknown all by his lonesome.
“Today, the exciting developments come out of interdisciplinary working groups, where participants can be of any age,” he told the Times in 2006. “I don’t know for sure, but I suspect that the leaders of teams making discoveries now are a lot older than they used to be. And that’s good. It’s a tragedy for society to spend decades training people and then depriving them of work at some arbitrary age.”