In announcing the award, the Nobel Assembly at Karolinska Institutet in Stockholm said the men “solved the mystery” of how cells organize their transport systems with timing and precision.
The researchers’ work, which was done separately (although Rothman and Schekman collaborated at one point early in their careers), revolves around tiny bubblelike structures called vesicles that act as cargo carriers. They showed that these bubbles act in a similar way in organisms as different as yeast and humans.
Concerns about cuts
While the honorees expressed gratitude for the prize, their comments about their work were tinged with worry about the future of biomedical research after years of cuts in federal funding.
Schekman, whose first major grant was from the National Institutes of Health in 1978, said winning the Nobel Prize made him reflect on how his original proposal might have fared in today’s depressed funding climate. “It would have been much, much more difficult to get support,” he said.
Likewise, Rothman wondered: “Would I have been able to have the initiative, to take the risk? I really am very concerned I would not have been.”
Südhof said that the funding situation in Washington “worries me tremendously.”
“I do think there’s a danger that . . . the system will stop and we won’t progress at the rate that would benefit our nation,” he said.
Schekman’s work began in the 1970s with yeast, a single-cell microorganism often used as a model for more complex life-forms. While investigating how vesicles move in and out of cells, he was able to identify 50 different genes involved in the process.
Schekman, who is also an investigator at the Howard Hughes Medical Institute, said he had known that his work was being considered for the prize but was still shocked when the call came — while he was sleeping. His wife picked up the phone and yelled to him, “This is it!”
Nobel Prize-winning discoveries often don’t have practical applications for 20 to 30 years after the awards are given out, but Schekman’s findings have already had a major impact on the biotech industry. Understanding cells’ molecular transport machinery allowed Novo Nordisk to tinker with baker’s yeast to make it produce insulin. And it helped lay the foundation for the development of Genentech’s cancer therapeutic Herceptin.
“I’m a firm believer in basic science and how that can be harnessed to understand disease processes,” Schekman said in an interview.
The brain’s chain reaction
Südhof, who was born in Germany, won the prize for work on the chain reaction of thousands of brain cells that have to be activated when, for instance, a baseball player analyzes a pitch and decides how to hit the ball. This type of action happens faster than the blink of an eye, in about four-tenths of a second.
Südhof — who receives funding from the Howard Hughes Medical Institute — found that when a nerve cell becomes active, it releases a chemical that hits another nerve cell, and so on.
“Until Thomas Südhof explained it, no one could explain how the brain could work that fast,” said Michael Brown, a University of Texas Southwestern Medical Center professor, who advised Südhof as a postdoctoral student in his lab. Brown himself won the Nobel Prize in medicine in 1985 with colleague Joseph Goldstein for work on how cholesterol levels are regulated in the blood and in cells.
Südhof, who is traveling in Spain, said in an interview that his interest in the brain developed while he was a medical student and that even though he ended up in basic research, his goal has always been to be able to treat disease.
He said he hopes his discoveries will lead to ways to counteract the loss of synapses; he thinks that would be the best chance to treat neurological conditions such as Parkinson’s disease, Alzheimer’s disease and schizophrenia.
“I am convinced that the general approach is the right way to get a treatment,” Südhof said. “I also believe it’s the only way.”
Rothman, chairman of Yale’s department of cell biology, discovered the process by which vesicles dock and fuse with their targets. Some of the genes Schekman discovered in yeast had counterparts in the genes Rothman was studying in mammals.
At a news conference at Yale, Rothman said that the research “opens the way to assess new drugs and better develop personalized medicine.”
Scott Emr, director of Cornell University’s Weill Institute for Cell and Molecular Biology, said the discoveries by the three men have implications across a wide range of fields.
“It’s absolutely spectacular news for us fundamental scientists who work in these areas,” he said. “I think recognition of this kind allows Congress and others to see how important it is to allow scientists to ask these relatively simple questions that ultimately allow us to understand the underpinnings of life itself.”