Photos: Courtesy of the Lasker Foundation
Few things are as rewarding as the academic lifestyle, says James E. Darnell Jr., a Rockefeller University researcher whose discoveries span an era of molecular biology. "The only thing I'd rather do is be first baseman for the Yankees, but seriously, I don't know any pursuit that gives you the joy that basic science does."
Arguably, recognition is a part of that joy. The Albert and Mary Lasker Foundation honored five scientists Friday, Sept. 27 at a ceremony in New York. Two scientists who elucidated the mechanisms of membrane trafficking, Randy W. Schekman and James E. Rothman, took home the Lasker Award for basic medical research. Willem J. Kolff and Belding H. Scribner, innovators behind the creation and application of kidney dialysis, received the Award for clinical medical research. Darnell received a special achievement award.
SPANNING AN ERA Darnell, a professor in the Laboratory of Molecular Cell Biology at Rockefeller, says it is hard to choose an achievement for which he is most proud. "I've had the good luck of discovering something in my seventh decade." Referring to his discovery of signal transducers and activators of transcription (STATs) while in his 60s, Darnell bridged the gap between cytokine signals outside the cell and transcription inside the nucleus.1 Two decades prior, Darnell was responsible for defining major classes of nuclear RNA, including precursors to messenger RNA. His work facilitated theories on posttranscriptional RNA processing, including those of Noble laureates Phillip Sharp and Richard Roberts. Darnell says he is privy to the care given in choosing Lasker winners--having served on the committee in the past. Twice, Darnell left when his discoveries were nominated. He did not win then but says that now he is "extraordinarily pleased," to be listed among the likes of Sydney Brenner and Paul Zamecnik, past winners of the special achievement award.
TRAFFIC JAMS Schekman, Howard Hughes Medical Institute investigator and professor of cell and molecular biology at University of California, Berkeley, and Rothman, chairman of cellular biochemistry at Sloan-Kettering Institute, New York, were drawn to membrane transport in the 1970s through the seminal work of George Palade. Palade charted the path for secretory vesicles from the endoplasmic reticulum, to the Golgi complex, to the surface of the cell. "To me," says Rothman, "it was almost unimaginable how a cell could carry out such a remarkable feat of internal organization with such obvious specificity." The question remained: how?
Schekman took a genetic approach, screening yeast mutations for secretory proteins. He and grad student, Peter Novick, isolated sec1, which, unlike wild types, showed a traffic jam of transport vesicles under the microscope.2 "That one image that I'll never forget made it clear that this was the direction of my work."
Rothman took a biochemical approach to the same problems by examining membrane proteins in mammalian cell lysates. He isolated the coat protein, COPI, involved in vesicle formation, and later SNARE (the SNAP REceptor) involved in directing the vesicles to their intended sites.3 Rothman, whose first lab was at Stanford University across the bay from Schekman, says he has valued his collaborator, competitor, and friend as their careers converged. Says Schekman, "About 15 years ago, the proteins that [Rothman] isolated turned out to be encoded by some of the genes that we had isolated. ... That was something I've called the golden spike experiment."
ARTIFICIAL INTELLIGENCE Two pioneering clinicians in the fields of hemodialysis and artificial organs were also honored this year: Kolff, distinguished professor emeritus at the University of Utah and SUNY Downstate in Brooklyn, NY, and Scribner, professor emeritus at the University of Washington. Kolff, who was unavailable for interview, invented the first artificial kidney to save patients with renal failure. Scribner says, "Everything: open heart surgery, artificial hearts, artificial kidneys, all really began with Kolff's work during the German occupation in the Netherlands in '44 and '45."
Scribner's contribution to hemodialysis came in the 1960s. Dialysis worked well for acute renal failure, but veins and arteries collapsed after a few treatments. After losing a patient to chronic renal failure says Scribner, "I woke up in the middle of the night and said, 'Boy, if we hooked the artery to the vein we could have permanent access.'" His idea was a U-shaped tube to shunt the flow of blood from artery to vein. Scribner, who could not attend the awards ceremony for health reasons, says, "I'm proud that we developed through trial and error the best way to treat a dialysis patient. The witness to that is the guy that's accepting my award. Robin Eady, a professor of a medical school in London, was started on dialysis in 1963--the world's longest survivor on renal replacement therapy."
Brendan A. Maher can be contacted at email@example.com.
1. N. Sankaran, "Cell biology/signal transduction," The Scientist, 9:15, Oct 2, 1995.
2. P. Novick et al., "Secretion and cell-surface growth are blocked in a temperature sensitive mutant of Saccharomyces cerevisiae," Proceedings of the National Academy of Sciences, 76:1858-62, 1979.
3. T. Sollner et al., "SNAP receptors implicated in vesicle targeting and fusion," Nature, 362:318-24, 1993.