Three U.S. scientists who won the Nobel Prize in Physiology or Medicine for insights on the transport system of cells said discoveries through basic research are threatened by government inaction and budget cuts.
James Rothman, 62, professor of biomedical sciences at Yale University; Randy Schekman, 64, professor of molecular and cell biology at the University of California, Berkeley; and Thomas C. Suedhof, 57, a physiology professor at Stanford University, yesterday won the prize for detailing how chemicals produced by cells are shuttled from one place to another. The work has led to new production methods for insulin and opened new avenues for treating disease.
The U.S. government shutdown, now in its second week, brought a halt to basic research at the National Institutes of Health. The agency also suspended grant applications. On March 1, President Barack Obama ordered the NIH to cut $1.55 billion, or 5 percent, of its 2013 budget. Science funding is “imperiled,” Suedhof said yesterday during a conference call.
“Particularly now people need to be reminded that that investment is being eroded and suspended because of government inaction,” Schekman said in an interview.
The three Nobelists credit their discoveries to the support of laboratory research that began without an obvious benefit to medicine. Still, their work on how cells shuttle hormones and other molecules from one area to another led to human insulin being made from yeast cells. That advance now accounts for a third of the world’s supply of insulin, Schekman said.
Chiron Corp., an Emeryville, California, company bought for $5.7 billion by Novartis in 2006, developed the techniques for using the scientists’ discovery to make medicinal proteins, Schekman said.
Support for basic research that can lead to new therapeutic techniques is on the wane, Rothman said.
“I had five years of failure before the first initial success,” Rothman said in an interview. “That kind of support, there’s less of it now. And that’s a pressing national issue.”
Schekman began researching how the cell’s transportation system works in the 1970s. He studied yeast, a single-celled organism, and found cells that experienced traffic jams, with packages of proteins piling up. The cause was genetic, and Schekman was able to identify the mutated genes involved in the congestion.
“Being able to study this in yeast made the discovery of the machinery responsible for doing this much simpler,” he said.
Rothman’s research in the 1980s and 1990s unveiled a protein complex that enables transporters in mammalian cells to dock and fuse with their targets, much like the two sides of a zipper. Some of the genes discovered by Schekman expressed proteins that corresponded to the proteins Rothman had found.
“We were studying the same thing by different means,” Schekman said. “It was very gratifying to realize that, while he studied mammalian cells growing in cell culture and my laboratory studied baker’s yeast growing in a broth, we would both uncover the exact same pathway with the very same molecules. All cells use this machinery to export molecules.”
Together, Rothman and Schekman mapped key components of the cell’s shipping system. For their work, they shared the 2002 Albert Lasker Basic Medical Research Award, sometimes called “America’s Nobel.”
Suedhof built on these findings in the 1990s by describing how cells know when to open the packages. Intrigued by how nerve cells communicate with each other in the brain, he searched for proteins that were sensitive to calcium, which was known to be involved in the process. He identified the machinery that was set in motion by an influx of calcium ions, opening the zipper and releasing the contents of the package.
“Through their discoveries, Rothman, Schekman and Suedhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo,” the Nobel Assembly said in a statement. “Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes and immunological disorders.”
In diabetes, for example, cells can’t ingest sugar because transporters that normally reside on the cell surface and import the sugar are stuck inside. Drugmakers could potentially improve insulin release and target the machinery that feeds the cell.
“This is a fundamental discovery of cell physiology,” Juleen Zierath, chairman of the Nobel Committee for Physiology or Medicine, said in a webcast interview. “They provide insight into disease progression and prospective treatments.”
Suedhof shared the Kavli Prize in Neuroscience in 2010 with Rothman and Richard Scheller of Genentech Inc., now part of Roche Holding AG, for their work revealing how signals between nerve cells are transferred in the brain. Suedhof and Scheller shared this year’s Lasker prize.
Suedhof was working in the laboratories of Michael Brown and Joseph Goldstein at the University of Texas Southwestern Medical Center at Dallas when the two men won the Nobel medicine prize in 1985. His laboratory at Stanford is studying how malfunctioning signals in the brain may contribute to disease such as Alzheimer’s and autism.
While the discoveries by Rothman, Schekman and Suedhof haven’t yet led to medicines, they have produced better diagnostics for disease, said Goeran K. Hansson, secretary of the Nobel Committee for Physiology or Medicine, at a news conference in Stockholm.
Rothman was born in Haverhill, Massachusetts, and holds an undergraduate degree from Yale University and a doctorate from Harvard University. Schekman, born in St. Paul, Minnesota, received his bachelor’s degree from the University of California, Los Angeles, and holds a doctorate from Stanford. Suedhof was born in Goettingen, Germany, and obtained his medical degree from the University of Goettingen in 1982. He is now a U.S. citizen.
Last year’s Nobel prize for medicine went to stem-cell pioneers John B. Gurdon and Shinya Yamanaka. Gurdon’s early work in transferring DNA between a tadpole and a frog paved the way in 1996 for the cloning of Dolly the sheep. Ten years later, Yamanaka turned mouse skin cells into stem cells with the potential to become any cell in the body.
Like Gurdon did after winning last year, Schekman urged governments to fund basic research.
“Our investment in basic science in this country is crucial,” Schekman said. “One can understand an important process that can be useful in biotech and other industries.”
Annual prizes for achievements in physics, chemistry, medicine, peace and literature were established in the will of Alfred Nobel, the Swedish inventor of dynamite, who died in 1896. The Nobel Foundation was established in 1900 and the prizes were first handed out the following year.
An economics prize was created almost seven decades later in memory of Nobel by the Swedish central bank. Only the peace prize is awarded outside Sweden, by the five-member Norwegian Nobel Committee in Oslo.
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