HEADLINE: NOBEL PRIZE AWARDED FOR WORK ON PROTEIN FUNCTIONS; MEDICINE: NEW
YORK
RESEARCHER'S DISCOVERY HAS LED TO BREAKTHROUGHS IN UNDERSTANDING SEVERAL
GENETIC DISEASES.
BYLINE: THOMAS H. MAUGH II, TIMES MEDICAL WRITER
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 63yearold 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 proteinsand 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.