Excursions with Paul Greengard

Nobel laureate, an expert on the neuron’s “inner world,” returns to where the work began.

The visit of Paul Greengard, Ph.D., to Yale in May was a homecoming of sorts for the Nobel laureate.

Greengard, who gave the 15th annual Farr Lecture on Student Research Day, spent 15 years working in a lab on the third floor of Sterling Hall of Medicine’s B wing before moving to Rockefeller University in 1983.

“The work which formed the foundation for the Nobel Prize was all carried out here at Yale,” said Greengard, who shared the 2000 Nobel Prize in physiology or medicine for his research into how nerve cells in the brain communicate. In a joking aside, he added, “Don’t tell the president of Rockefeller I said that.”

Greengard said that when he started the work shortly after coming to Yale, “one of the things that our research was most interested in was to try to elucidate the mechanism by which neurotransmitters activate receptors.” One school of thought argued that electrical impulses drove communications among neurons. An opposing view held that neuronal communications were mediated by a chemical process. The chemical view eventually won out, and Greengard’s research led to his discovery of the role of phosphorylation in the mechanism of action of neurotransmitters.

While at Yale, he came close to making a serious error. In 1978 a young scientist wrote and asked for a position in his lab as a postdoc. “I wrote back and said no,” Greengard said. “It was probably the dumbest thing I had ever done.” Five days later Greengard had a visit from cell biology Chair George Palade, M.D., who had won the Nobel in 1974. “He came into my office and said, ‘You made a big mistake.’ He was God at that time. He told me how bad the mistake was, and I reversed my decision.”

The young postdoc was Pietro De Camilli, M.D., now a professor and former chair of cell biology himself, who introduced Greengard to a standing-room-only crowd in the auditorium of the Jane Ellen Hope Building. “He discovered the inner world of the neuron,” De Camilli said of his former mentor.

Greengard’s talk capped a day of poster and oral presentations by students. Five students made oral presentations and 65 had posters on the walls of the Hope Building. While slightly more than half of the posters described the results of laboratory work, the range of research questions was quite broad, delving into the basis of absolute pitch, conflicts of interest in medical research, the risk of injury to children in Pakistan and supports and barriers to the use of health care interpreters for patients with limited English.