Reuters
From left: Randy W. Schekman, Thomas C.
Südhof and James E. Rothman.
Three Americans won the Nobel Prize in
Physiology or Medicine on Monday for discovering the machinery that regulates
how cells transport major molecules in a cargo system that delivers them to the
right place at the right time.
The Karolinska Institute in Stockholm
announced the winners: James E. Rothman, 62, of Yale University; Randy W.
Schekman, 64, of the University of California, Berkeley; and Dr. Thomas C.
Südhof, 57, of Stanford University. Their basic research solved the mystery of
how cells, which are factories producing molecules, organize a system to
transport the molecules within cells and export them outside.
As it turns out, the molecules are moved around the
cell in small packages called vesicles, and each scientist discovered different
facets of what is needed to ensure that the right cargo is shipped to the
correct destination at precisely the right time. For example, pancreatic cells
make insulin and release it in the blood. Chemical signals called
neurotransmitters are sent from one nerve cell to another to allow people to
walk, talk, sing, pull their hand away from a hot stove and communicate. The
molecular traffic within cells is as complicated as rush hour in any city, as
the discoveries by the three Nobel winners revealed.
The world’s most prestigious scientific award arrived
at a particularly dark time for federal science research: the National
Institutes of Health, the agency that paid an estimated $49 million to help
underwrite the winners’ work, has been forced to send home most of its staff
because of the government shutdown. Basic research of the type that just won the
Nobel is seen as particularly vulnerable to Capitol Hill budget cutters.
“This is a stark reminder of how these are the best of
times and the worst of times for American biomedical research,” Dr. Francis
Collins, the N.I.H. director, said in an interview on Monday. “Today we
celebrate the three N.I.H.-supported Nobel Prize winners, but we’re being
slammed by sequestration and a government shutdown.”
Even before the shutdown, scientists were facing
severe budgetary difficulties that restrict the kind of research that led to
this year’s Nobel Prize, Dr. Collins noted. “How many potential future Nobel
Prize winners are struggling to find research support today, or have been sent
home on furlough?” he said. “How many of them are wondering whether they should
do something else — or move to another country? It is a bitter irony for the
future of our nation’s health that N.I.H. is being hamstrung this way, just when
the science is moving forward at an unprecedented pace.”
One of the new laureates, Dr. Rothman, touched on this
point in a news conference, saying that he began his scientific career when
“your idea was the only limit, any risk could be taken no matter how difficult.”
He experienced five years of failure before the first signs of success, he said.
Today, he said, there is less support for risk ideas, “and it is becoming a
pressing national issue, if not an international one.”
All three laureates said they undertook their research
amid skepticism from scientific leaders.
Dr. Schekman discovered a set of genes that were
required for vesicle traffic. Dr. Rothman unraveled protein machinery that
allows vesicles to fuse with their targets to permit transfer of cargo. Dr.
Südhof revealed how signals instruct vesicles to release their cargo with
precision.
The tiny vesicles, which have a covering known as a
membrane, shuttle the cargo between different compartments or fuse with the
membrane. The transport system activates nerves. It also controls the release of
hormones and enzymes. Disturbances in this exquisitely precise control system
for transporting and delivering cellular cargo cause serious damage that, in
turn, is believed to contribute to some neurological diseases, diabetes and
immunological disorders.
Dr. Schekman, who was born in St. Paul, Minn., used
one-celled yeast as a model system when he began his research in the 1970s. He
found that vesicles piled up in parts of the cell and that the cause of the
congestion was genetic. He went on to identify three classes of genes that
control different facets of the cell’s transport system. A graduate of the
University of California, Los Angeles, and Stanford, where he obtained his Ph.D.
in 1974, Dr. Schekman joined the faculty at Berkeley in 1976. His findings
enabled the biotechnology industry to exploit the secretion system in yeast to
create and spit out pharmaceutical and industrial products like insulin and
hepatitis B vaccines.
Dr. Rothman, who was born in Haverhill, Mass., studied
vesicle transport in mammalian cells in the 1980s and ’90s. He discovered that a
protein complex allows vesicles to dock and fuse with their target membranes.
During the fusion, proteins on the vesicles and target membranes bind to each
other like the two sides of a zipper. The fact that there are many such proteins
and that they bind only in specific combinations ensures that cargo is delivered
to a precise location; the same principle operates inside the cell and when a
vesicle binds to the cell’s outer membrane to release its contents.
Dr. Rothman received a Ph.D. from Harvard Medical
School in 1976 and was a postdoctoral fellow at the Massachusetts Institute of
Technology. In 1978, he moved to Stanford, where he started his research on the
vesicles of the cell. He has worked at Princeton University, the Memorial
Sloan-Kettering Cancer Center and Columbia University. In 2008, he joined the
faculty of Yale, where he is chairman of the department of cell biology.
Dr. Südhof, 57, a United States citizen who was born
in Göttingen, West Germany, studied neurotransmission, the process by which
nerve cells communicate with other cells in the brain. He helped transform what
had been a rough outline into a number of molecular activities to provide
insights into the elaborate mechanisms at the crux of neurological activities,
from the simplest to the most sophisticated. A graduate of the
Georg-August-Universität in Göttingen, he moved to the University of Texas
Southwestern Medical Center in Dallas in 1983 and became an investigator at the
Howard Hughes Medical Institute in 1991. In 2008, he was appointed professor of
molecular and cellular physiology at Stanford.
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