Guenter Blobel, a cell biologist at Rockefeller University in New York, was awarded the Nobel Prize in Physiology or Medicine yesterday for discovering how proteins get shipped to their proper destinations within the body after being manufactured by tiny molecular factories inside cells.
Blobel, 63, showed in the 1970s that each of the thousands of proteins made inside the body's trillions of cells bears a distinctive sequence, very much like a Zip code or the three-letter destination codes that appear on airline baggage tags.
In a series of intricate and elegant experiments conducted with molecular tools that were blunt and cumbersome by contemporary standards, Blobel identified and deciphered those destination sequences. He also discovered how various helper molecules inside cells "read" the codes and deliver the proteins to their proper addresses.
"It was a big challenge, and sometimes we were tempted to do something else, but we stuck with it," Blobel said. "There were peaks of excitement that kept us going."
Blobel's research laid important groundwork for the burgeoning biotechnology industry, which today makes routine use of his discoveries to manufacture medicines inside living cells instead of in laboratory flasks.
Other researchers have built on Blobel's findings to create gene therapies for rare diseases caused by defects in the body's protein-addressing system. In those diseases, proteins get delivered to inappropriate compartments within cells, or even to entirely wrong parts of the body.
"I can't think of anyone more deserving than Guenter," said Ira Mellman, a cell biologist at Yale University School of Medicine who has known and worked with Blobel for many years. "There is this unbelievable substance to his scientific work, which can be measured not only in terms of what he has done but by the number of young scientists who have passed through his lab and become important scientists in their own right. In scientific culture, that's what immortality is."
Awarded by the Nobel Assembly at the Karolinska Institute in Sweden, the prize is worth $960,000 this year. Blobel, who a few years ago founded a global charity dedicated to restoring the Frauenkirche, the beautiful Baroque cathedral that was shattered in the bombing of Dresden in 1945, told news services he will donate some of his winnings toward that $150 million restoration, scheduled for completion in 2006, the 800th anniversary of the founding of Dresden. He said he will donate the rest of the prize money to help reconstruct the Dresden Synagogue and another destroyed landmark building in the Italian village of Fubine.
Blobel is a tall and imposing man with brilliant white hair, well known for being more nattily dressed than most scientists. Colleagues yesterday described him variously as "opinionated," "tempestuous," "intimidating," and someone who has "rubbed a lot of people the wrong way," but also as "a scholar," "a great scientist" and "a Renaissance man."
"If you worked at MGM Studios and you wanted a model scientist from Central Casting, it would be him," Mellman said.
Ten years ago, after a tiff with the National Institutes of Health over the bureaucratic hassles of its grant review process, Blobel simply stopped dealing with the agency -- which had backed his early work with more than $4.5 million in grants -- and never asked for another penny. His work has been supported for the past 13 years by the Howard Hughes Medical Institute, based in Chevy Chase, known for its generous support of top scientists.
Blobel, now an American citizen, came to the United States as a PhD student in the early 1960s. A decade later he began to tackle the vexing question of how proteins get to their destinations in cells.
Proteins, including hormones, enzymes and other key molecules of life, are long strands of amino acids that resemble the beaded pull chains that hang from overhead light fixtures. They are assembled one amino acid at a time in tiny production facilities called ribosomes, which work from blueprints called genes. The proteins fold themselves into convoluted bundles and then go to their job sites.
In some cases those destinations are particular compartments, or "organelles" (such as the mitochondria or the nucleus), inside the same cell in which the protein was made. In other cases the destination might be an entirely different part of the body, in which case the protein must enter a canal and be secreted by the cell for long-distance delivery to a different tissue or organ.
Blobel attached radioactive tracers to newly made proteins, then tracked their movements inside test tubes filled with various organelles. He found that new proteins bear a few extra amino acids, apparently tacked on by the ribosome according to specifications in the protein's genetic code. Those amino acids act as destination tags, which can be "read" by roaming molecules called signal recognition particles, which in turn deliver the proteins to key transport channels or other destinations bearing matching codes.
Blobel also showed that this mechanism operates virtually identically in plants, animals and fungi -- a discovery that now allows scientists to use bacteria and yeast as factories that secrete human drugs and other useful proteins. About 350 of the approximately 1,000 new drugs now being tested in patients are products of biotechnology, according to the Pharmaceutical Research and Manufacturers of America.
"He's the granddaddy of this field," said Arthur Horwich, a Yale University cell biologist and geneticist who studies protein traffic. "His Zip code concept was a major idea that inaugurated a whole field of investigation with some real practical spinoffs. He anticipated what was going on years before the rest of us tuned in completely."