Inside Salk - July 2012 - page 8

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Lead Story
Inside Salk 07|12
SalkCancer Research
Milestones
1950s
Renato Dulbecco
and
Marguerite Vogt
describe how a tumor virus can "turn on"
the uncontrolled growth that is the hall-
mark of cancer, providing an important
clue to the genetic nature of cancer.
1970
Salk Cancer Center is established under
the direction of Nobel laureate
Robert
Holley
. Salk professor
Leslie Orgel
discovers a straightforwardway to
synthesize cytosine arabinoside (Ara C),
a compound that becomes one of today's
most commonly used anti-cancer agents.
1972
TheNational Cancer Institute designates
the Salk center as one of the first seven
basic cancer centers in theUnited States.
1975
Dulbecco shares the Nobel Prize in
Physiology andMedicine withHoward
Temin and
DavidBaltimore
.
1979
Tony Hunter
discovered a process called
tyrosine phosphorylation turns out to be
the underlying cause of many types of
human cancer, a discovery that leads
to the development of the leukemia
drug Gleevec.
Dulbecco was a wonderful mentor.”
The Salk Cancer Center’s focus on the genetics of cancer and cellular processes began
withDulbecco, Eckhart says. “He was always ahead of his time,” he says. “He had the big
picture inmind.”
Four of the investigators who trained or workedwithDulbecco at Salk were later awarded
Nobel Prizes. Susumu Tonegawa, a 1987winner, was a postdoctoral fellowwithDulbecco
working on transcription by SV40. LeeHartwell, also a postdoctoral fellow inDulbecco’s
lab, eventually switched fromworking on polyomavirus to yeast, which led to his work on the
genetics of cell division and his 2001Nobel Prize. Paul Berg, a 1980 Nobel laureate, spent
a year in Dulbecco’s lab, conducting research that led to developing SV40 as a vector for
introducing new genes into mammalian cells using recombinant DNA techniques.
David
Baltimore
, a Salk Non-Resident Fellow and president emeritus of the California Institute
of Technology, who conducted research at Salk for three years, credits Dulbecco for his influ-
ence in setting the direction of Baltimore’s later work onmammalian tumor viruses. Although
the problem he worked onwas separate fromDulbecco’s investigation, Baltimore says he was
clearly influenced by Dulbecco’s clarity of thought.
legacyofdiscovery
The Salk Institute Cancer Center was established in 1970 under the direction of
Robert Holley
, who had received theNobel Prize two years earlier, and in 1973, theNational
Cancer Institute designated the Salk center as one of the first seven basic cancer centers
in theUnited States.
Dulbecco left Salk in 1972, moving to Londonwith his wife, Maureen, and their young
daughter, Fiona, to serve as deputy director of research at the Imperial Cancer Research
Fund Laboratories. At Salk, four of the original faculty appointed to the Tumor Virology
Laboratory set up their labs in Dulbecco’s previous research space—
Walter Eckhart
,
Gernot Walter
,
Bertold Francke
and
Tony Hunter
—and worked on polyomaviruses as a
model for human cancer.
Their work spawned a number of key findings at Salk, includingHunter’s discovery that
tyrosine phosphorylation is a chemical “on-off” switch responsible for telling cells to
become cancerous. Discovery of this important signalingmechanism, which proved to be
the underlying cause of many types of human cancer, revolutionized cancer medicine and
ultimately led to the development of several innovative cancer therapies, including the
leukemia drug Gleevec.
Dulbecco returned to Salk in 1977 and launched a new research program focused on
breast cancer. He usedmonoclonal antibody technology to identify proteins found on the
surface of normal mammary cells. This provided important insights into the normal
development of mammary glands and allowed him to study howmutagensmight cause
mammary cells to become cancerous.
Dulbecco closed his laboratory to serve as Salk’s president from1988–92. After winning
theNobel Prize in 1975, he used his influential voice to speak out for fundamental changes
Renatowas agiant of cancer biology,
and he did not shy away frommaking
bold, visionary statements.
– INDER VERMA
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