Nobel Prize Awarded for Work on Protein Functions
A German American researcher who discovered how the body puts “addresses” on individual proteins so that they arrive at the correct location has been awarded the 1999 Nobel Prize for medicine or physiology.
The discoveries have helped scientists unravel the causes of several genetic diseases, including cystic fibrosis and familial hypercholesterolemia, according to the Nobel Foundation citation. Dr. Guenter Blobel of the Howard Hughes Medical Institute at Rockefeller University in New York City found that each of the 1 billion protein molecules in a single cell bears a short address tag. The tag indicates that it belongs in the nucleus, the cell membrane or elsewhere, or that it should be secreted outside the cell.
With such tags, the cell runs like a well-organized factory. Without them, it would be like an earthquake-damaged warehouse with cellular components scattered uselessly about.
When proteins are sent to the wrong location by a defective tag, they cannot perform their customary function and can produce disease.
In familial hypercholesterolemia, for example, a very high level of cholesterol occurs in the blood because proteins that would normally remove it are not where they should be. Understanding why that happens, Blobel noted, is the first step toward developing a treatment.
The findings have also contributed to the development of a more effective use of cells as protein factories for the production of important drugs.
Blobel’s work “has led to an explosion of knowledge on the [movement] of proteins in the cell, and even on the way some kinds of drugs may be introduced into cells,” said Marvin Cassman, director of the National Institute of General Medical Sciences in Bethesda, Md.
Blobel, a 63-year-old native of Waltersdorf, a city that was in Germany when he was born but is now in Poland, has worked in the United States since the early 1960s and became a U.S. citizen in the 1980s.
He said Monday that he will donate the $960,000 prize toward the restoration of a synagogue and the famed Frauenkirche (Church of Our Lady) in Dresden, Germany, a city that was destroyed by Allied firebombing in World War II when he was 8. At a news conference, he described viewing the city’s skyline just before the attacks began and later after the terrible destruction had been wrought.
“It left a tremendous impression on me,” he said.
Blobel is a founder of Friends of Dresden, which has already raised more than $1 million for restoration of historic structures in the city.
The tall scientist with a shock of white hair said that when the phone call from the Nobel Foundation came at 5 a.m., “I thought it might be a prank by one of my colleagues. I slowly felt confident this was real.”
After finally hanging up, he and his wife, Laura, hugged each other, he said.
Blobel was cited for work that for the first time explained how the internal structure of cells is maintained--particularly with respect to proteins. Proteins are complex molecules, composed of amino acids, that are the primary building blocks for construction of a cell. They also carry out chemical reactions--such as the construction of other proteins--and serve as signaling agents.
Before Blobel’s work, it was unknown how newly made proteins were directed to their correct locations in the cell and how large proteins could traverse the tightly sealed membranes surrounding individual structures within the cell. About the only thing that was known, according to Dr. Donald Steiner of the University of Chicago, was that newly synthesized proteins were a little bit longer than expected.
Blobel speculated in 1971 that this extra section of protein was a tag signaling the protein’s ultimate destination. Over the next several years, Steiner said, “he provided clear, elegant, decisive experimental evidence that showed exactly how this signal . . . was functioning.”
Blobel’s hypothesis and subsequent proof of the concept was a seminal insight into cellular functioning, added molecular biologist Danny Schnell of Rutgers University. “The rest of us have just come along and filled in the details.”
The system has subsequently been shown to be universal, functioning in plants, animals and microorganisms as well as humans.
Blobel cautioned that his discoveries do not have the immediate medical implications of the work of some other Nobel Prize winners. “It’s not a cure for AIDS, it’s not a cure for Alzheimer’s,” Blobel said. “It’s basic biological research.”
But it does have implications for medical research. Biotech companies now add protein address codes to genes inserted into yeast or bacteria for producing drugs, so that the desired product will be secreted by the microorganism.
*
Times staff writer John Goldman in New York City contributed to this story.
