Lasker Prizes Given for Discoveries in Cancer and Genetics, and for Ebola Response
The Lasker awards, among the most respected prizes in medicine, will go to three scientists who made groundbreaking discoveries in cancer andgenetics, and to the aid group Doctors Without Borders, the Albert and Mary Lasker Foundation announced Tuesday.
The awards, given in three categories, each with a prize of $250,000, will be presented in Manhattan on Sept. 18. Many Lasker recipients have gone on to receive Nobel Prizes, including 44 in the last three decades, according to the foundation.
Evelyn M. Witkin and Stephen J. Elledge shared the Albert Lasker Basic Medical Research Award for work they did independently of each other on the “DNA-damage response” — an array of actions that bacteria, yeast and human cells take to protect their genomes against an endless barrage of threats from chemicals, radiation and normal biochemical processes that go awry.
James P. Allison received the Lasker-DeBakey Clinical Medical Research Award for discovering and developing a cancer treatment that became the first of a new class of drugs called checkpoint inhibitors, which work by unleashing the immune system to fight cancer.
Doctors Without Borders (Médecins Sans Frontières in French) was given the Lasker-Bloomberg Public Service Award for “bold leadership” in fighting the Ebola epidemic in West Africa, “and for sustained and effective front-line responses to health emergencies,” the Lasker Foundation said in a statement.
Dr. Witkin, 94, is a bacterial geneticist and professor emerita at the Waksman Institute of Microbiology at Rutgers University. She began her career in the 1940s with investigations of genetic mutations in bacteria.
By the late 1960s, Dr. Witkin had discovered how ultraviolet light caused mutations in the bacteria E. coli. The ultraviolet rays caused changes in the DNA that prompted the cell to produce a new type of DNA-copying enzyme. But the new enzyme — called a “sloppier copier” by another scientist — tended to make mistakes. And those mistakes were mutations.
In the early 1970s, Dr. Witkin said in an interview, she began to collaborate with Miroslav Radman, from the Free University of Brussels.
“We pooled our information and decided that this was the tip of a very interesting iceberg,” Dr. Witkin said. “E. coli was inducing a large number of activities when the DNA was damaged.”
Eventually, she and Dr. Radman proposed “the S O S hypothesis,” meaning that DNA damage generates a distress signal that touches off a biological cascade of rescue efforts.
The response is now known to include 43 genes that turn on when DNA is damaged, Dr. Witkin said. Their purpose is to increase DNA repair and many other activities that help the cell survive and reproduce.
During the 1980s, Dr. Witkin said, she became impressed with the research of a graduate student she had never met who was also studying the DNA damage response in yeast, and who later moved on to human cells. “It was beautiful work,” she said. “I admired it.”
That graduate student was Dr. Elledge, whom she finally met just recently.
“I’m proud to be sharing the award with him,” Dr. Witkin said.
Dr. Elledge, 59, is a professor of genetics and medicine at Harvard Medical School and the Brigham and Women’s Hospital in Boston. Much of his research focuses on the genes and proteins involved in sensing and responding to DNA damage, and their roles in cancer and degenerative disorders of the nervous system.
“You’re basically melting away every day,” he said in an interview. “Your DNA is under attack.”
There are thousands of threats to each cell every day, he said. But the DNA damage response means much more than just DNA repair, he said. It also involves alerting the immune system and activating other survival mechanisms.
“DNA damage is information,” Dr. Elledge said. “DNA has evolved the ability to sense its own integrity. This is inside a cell, like chemical intelligence.”
Dr. Allison, 67, is a professor of immunology, chairman of the immunology department and executive director of the immunotherapy platform at the University of Texas M.D. Anderson Cancer Center in Houston.
Much of his research concerns T cells, a type of white blood cell that is sometimes described as a soldier of the immune system, deployed to seek and destroy invaders. For years, scientists tried to find ways to turn T cells against cancer, with little success.
In the 1990s, Dr. Allison and Dr. Jeffrey Bluestone, of the University of California, San Francisco, showed independently that a protein on T cells actually subdued the cells, apparently to dial back their ferocious activity and prevent autoimmune disorders.
Dr. Allison wondered if it might be possible to unleash the T cells against cancer by blocking the protein — which came to be called a checkpoint — that was hobbling the cells. He and a postdoctoral fellow, Dana Leach, developed an antibody that could block the protein. In mice with cancer, it worked to turn T cells against tumors.
Many drug companies were skeptical, but one, Medarex, created a human version of the antibody, called ipilimumab. Medarex was later acquired by Bristol-Myers Squibb, and the antibody, given the trade name Yervoy, was approved in 2011 to treat advanced melanoma.
It became the first drug to prolong survival in people with this deadly form of cancer. Researchers have reported that among 5,000 people treated, about 22 percent were alive 10 years later.
Other researchers have discovered additional checkpoints, and two more inhibitors have been approved for melanoma and a type of lung cancer. The drugs are being tested against many other types of cancer.
Dr. Allison said in an interview that the focus of his research now was to understand precisely how the checkpoint inhibitors worked and how they could be used in combination with one another and with other cancer drugs.
“The goal is to extend the number of tumor types that respond and find the proper combinations to get as many durable responses as we can,” he said. “It’s an exciting time.”
The award citation to Doctors Without Borders said that the group had taken on the “monumental” task of fighting Ebola in West Africa, “a duty that rightly belongs to the international community” and not to an aid group funded mostly by donors.
Despite numerous warnings from the group in early 2014 about the outbreak’s scope and severity, the World Health Organization and the international community were slow to respond, and the disease spiraled out of control. More than 11,000 people have died.
The epidemic is waning, but Doctors Without Borders remains in the region, building maternity and pediatric hospitals, vaccinating children, treating malaria and other local illnesses and providing mental health care. The group received the Nobel Peace Prize in 1999.
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