Paul Greengard was born on December 11, 1925, in New York City. During World War II, he served in the United States Navy as a electronics technician at the Massachusetts Institute of Technology working on an early warning system to detect Japanese kamikaze planes. After the war, he attended Hamilton College where he graduated in 1948 with a bachelor's degree in mathematics and physics. He decided against graduate school in physics because most post-war physics research was focusing on nuclear weapons, and instead became interested in biophysics. He began his graduate studies at Johns Hopkins University in the lab of Haldan Keffer Hartline. Inspired by a lecture by Alan Hodgkin, Greengard began work on the molecular and cellular function of neurons. In 1953, Greengard received his PhD and began postdoctoral work at the University of London, Cambridge University, and the University of Amsterdam.
As a professor, he has worked at the Albert Einstein College of Medicine, Vanderbilt University, Yale University, and Rockefeller University.
In 2000, Greengard, Arvid Carlsson and Eric Kandel were awarded the Nobel Prize for Physiology or Medicine for their discoveries concerning signal transduction in the nervous system.
Greengard's research has focused on events inside the neuron caused by neurotransmitters. Specifically, Greengard and his fellow researchers studied the behavior of second messenger cascades that transform the docking of a neurotransmitter with a receptor into permanent changes in the neuron. In a series of experiments, Greengard and his colleagues showed that when dopamine interacts with a receptor on the cell membrane of a neuron, it causes an increase in cyclic AMP inside the cell. This increase of cyclic AMP, in turn activates a protein called protein kinase A, which turns the function other proteins on or off by adding phosphate groups in a reaction known as phosphorylation. The proteins activated by phosphorylation can then perform a number of changes in the cell: transcribing DNA to make new proteins, moving more receptors to the synapse (and thus increasing the neuron's sensitivity), or moving ion channels to the cell surface (and thus increasing the cell's excitability).
The following press release from the Royal Swedish Academy of Sciences describes Greengard's work:
In the human brain there are more than hundred billion nerve cells. They are connected to each other through an infinitely complex network of nerve processes. The message from one nerve cell to another is transmitted through different chemical transmitters. The signal transduction takes place in special points of contact, called synapses. A nerve cell can have thousands of such contacts with other nerve cells.
The three Nobel Laureates in Physiology or Medicine have made pioneering discoveries concerning one type of signal transduction between nerve cells, referred to as slow synaptic transmission. These discoveries have been crucial for an understanding of the normal function of the brain and how disturbances in this signal transduction can give rise to neurological and psychiatric diseases. These findings have resulted in the development of new drugs.
Paul Greengard, Laboratory of Molecular and Cellular Science, Rockefeller University, New York, is rewarded for his discovery of how dopamine and a number of other transmitters exert their action in the nervous system. The transmitter first acts on a receptor on the cell surface. This will trigger a cascade of reactions that will affect certain "key proteins" that in turn regulate a variety of functions in the nerve cell. The proteins become modified as phosphate groups are added (phosphorylation) or removed (dephosphorylation), which causes a change in the shape and function of the protein. Through this mechanism the transmitters can carry their message from one nerve cell to another.