Thunderstorm, 60° F
Jack Szostak,
a genetics professor at Harvard Medical
School and Harvard-affiliated Massachusetts
General Hospital (MGH), has won the 2009 Nobel
Prize in physiology or medicine for pioneering work in the discovery of telomerase, an enzyme that protects chromosomes from degrading.
The work not only revealed a key cellular function, it also illuminated
processes involved in disease and aging.
Szostak, the Alex Rich Distinguished Investigator in the MGH
Department of Molecular Biology, called the prize “the highest scientific honor” and
thanked his co-winners and collaborators, Elizabeth H.
Blackburn of the University of California, San Francisco, and Carol
W. Greider of Johns Hopkins University School of Medicine.
“It started off as work on a very basic question that has turned
out, to our delight and surprise, to have much broader implications,” Szostak
said.
The three won the prize for work conducted during the 1980s
to discover and understand the operation of telomerase, an enzyme that forms
protective caps called telomeres on the ends of chromosomes.
Subsequent research has shown that telomerase and telomeres
hold key roles in cell aging and death and also play a part in the aging of the
entire organism. Research has also shown that cancer cells have increased
telomerase activity, protecting them from death.
Harvard President Drew Faust congratulated Szostak, saying
his achievement highlights the importance of basic scientific research, which
may not have an apparent practical application when it is conducted.
“I congratulate Jack Szostak and his colleagues on this singular honor,” Faust
said. “Their work has not only shed light on the central scientific issues of
aging and disease, it also clearly illustrated the importance of unfettered
basic research.”
Harvard Medical School Dean Jeffrey Flier said the work
highlights not just the importance of basic research, but also that of the
ongoing collaboration between the University and its hospitals — in this case,
Harvard Medical School’s Department of Genetics and MGH’s Department of
Molecular Biology, where Szostak holds appointments.
“These two units have worked together in tremendous and
beautiful synergy, scientifically, for so many years, and have been a breeding
ground for so many scientific breakthroughs, including those being recognized
today,” Flier said. “The things [Szostak] did to understand how yeast cells
work are now leading to what we think are going to be important breakthroughs
in therapies for cancer, approaches to aging, and [important in] many other human
diseases.”
MGH President Peter Slavin said the hospital was “thrilled
and honored” to learn of Szostak’s award and thanked him for his contributions
to biomedical research and for advancing the understanding of human biology and
disease.
Robert Kingston, chief of MGH’s Department of Molecular
Biology, called Szostak “a scientist’s scientist” with an “absolutely
remarkable record of scientific achievement.”
“Jack is among a handful of the most respected scientists in
the field,” Kingston said. “He’s immensely, immensely deserving of this
recognition.”
In addition to being a professor of genetics at Harvard
Medical School, and a member of MGH’s Center for Computational and
Integrative Biology, Szostak is a Howard Hughes Medical
Institute investigator.
Szostak’s day began at 4:45 a.m. with a phone call from the
Nobel Assembly at Karolinska Institutet in Sweden, which awards the prize. By
midday, he said, his phone still hadn’t stopped ringing.
Later Monday, Szostak missed the introductory biochemistry
class he was scheduled to teach and appeared instead at a news conference at
Massachusetts General Hospital’s Simches Research Center. He entered the room,
beaming, to a standing ovation by colleagues from the hospital.
Matthew Powner, a postdoctoral fellow in Szostak’s
laboratory on the building’s seventh floor, said he and the rest of the lab
were excited for Szostak. The lab was decorated with congratulatory notes,
ribbons, and gold balloons.
“I think it’s fantastic news,” Powner said.
Telomeres’ existence was hypothesized in the 1930s after scientists observed
that, though the ends of normal chromosomes never fuse with each other, the
ends of chromosome fragments do. In 1980, Szostak began collaborating with
Blackburn. Together they showed that repeated nucleotide sequences found in
telomeres of a single-celled protozoan also worked to protect chromosomes in
yeast cells, illustrating they had discovered something very basic that worked
in a wide range of creatures.
Blackburn
and Greider went on to isolate telomerase, while Szostak identified a protein
essential for maintaining telomeres in yeast, which turned out to be a key component
of the enzyme. His work showed that the inability to add nucleotide repeats to
chromosomes led to telomere shortening and eventually cell death. This was
the first link between the molecular biology of telomeres and cellular
senescence, the aging and death of cells.
Although
this work was not known to be relevant to human disease when carried out in the
1980s, subsequent studies of telomeres and telomerase in human cells have shown
that the enzyme plays crucial roles in both cancer and aging.
Since his work on telomeres and telomerase, Szostak has
shifted focus. Today he is exploring the very beginnings of life, focusing on
how the first cells were created. He is co-director of Harvard’s Origins
of Life Initiative. That work caused Harvard Provost and HMS neurobiology professor Steven E. Hyman to say that
“since his Nobel prize-winning work with telomeres, Jack Szostak has, if anything, become more creative. His work on the origins of life is exciting and inspiring and, just perhaps, may win him another” prize. (Here’s an image of a simple protocell model created in the Szostak lab as part of its ongoing “origins” work.)
With Szostak’s award, 44 current and former Harvard faculty
members have been recipients of Nobel Prizes for wide-ranging work, including
the tissue culture breakthrough that led to the creation of the polio vaccine,
negotiations that led to an armistice in the 1948 Arab-Israeli War, the first
description of the structure of DNA, pioneering procedures for organ
transplants, and the development of Gross National Product as a measure of national
economic change.
The most recent Harvard faculty member to win a Nobel Prize
was in 2005, when physicist Roy
Glauber received the physics Nobel for work on the nature and behavior of
light and Thomas Schelling won in economics for work on conflict and
cooperation in game theory. Previous winners this decade include Linda Buck,
in physiology or medicine in 2004, Richard Giacconi, in physics in 2002, and A. Michael Spence, in economics in 2001.
