Günter Blobel, Nobel Laureate Who Found Cell ‘ZIP Codes,’ Dies at 81

Günter Blobel, a molecular biologist who was awarded the 1999 Nobel Prize in Medicine for discovering that proteins in any living cell have virtual ZIP codes that guide them to where they can help regulate body tissues, organs and chemistry, died Sunday in New York. He was 81.

A spokeswoman for Rockefeller University in Manhattan, where he had long conducted his research, confirmed his death, at New York-Presbyterian Weill Cornell Medical Center, and said the cause was cancer.

Because all diseases have a molecular basis, medical experts say, Blobel’s achievement was a fundamental step on the road to improved health, holding out the promise of understanding the mechanisms behind cystic fibrosis, Alzheimer’s disease, leukemia, schizophrenia, the virus that causes AIDS and other immune-system deficiencies, hereditary conditions and cellular aberrations, including cancers.

A Silesian-born boy in Nazi Germany during World War II, and later a refugee from postwar communism in East Germany, Blobel (pronounced BLO-bull) set out to be a physician in America but found himself increasingly drawn to pure research. He spent nearly all his working life at Rockefeller University, what he regarded as the valhalla of research.

Like many scientific advances, Blobel’s had no moment of “Eureka!” It unfolded over 30 years of painstaking, often frustrating, but occasionally thrilling investigation: a process of building on others’ work, intuitive thinking to form new hypotheses, and testing, using the results to modify his theories, and then testing and modifying again and again.

Driven to find underlying causes of diseases that were being treated for symptoms, and funded by the National Institutes of Health and the Howard Hughes Medical Institute, he successively developed five models of his original “beautiful idea.” Along the way he won many prestigious awards, some for essentially the same insights recognized later by the Nobel committee.

It was all terribly complicated. As Blobel liked to tell ordinary people, “To greatly simplify ...”

To greatly simplify, Blobel built on the work of his Rockefeller University mentor, Dr. George E. Palade, a pioneer in using electron microscopes; Palade shared the 1974 Nobel Prize in physiology or medicine, as the award is formally called.

Palade’s discoveries about cells’ inner workings, and the functions of cell structures, laid the foundations of modern cell biology, the basis of the biotechnology industry.

Blobel, who joined Palade’s laboratory in 1967, inherited from his scientific forebears the knowledge that each living cell — about 1 quadrillion of them in an adult human body — contains 1 billion protein molecules that are constantly being created inside tiny bladder-like cavities called the endoplasmic reticulum, which is encased in a protective membrane.

The mystery Blobel confronted was how cells control their internal traffic, so that large proteins can get through tightly sealed membranes surrounding their birthplace and then travel to sites within the cell, or even through cell walls on intercellular trips through the body, where they can find specific worksites, called organelles (little organs) and penetrate them to perform assigned tasks.

In 1971, Blobel and a colleague, Dr. David D. Sabatini, who later headed cell biology studies at the New York University School of Medicine, proposed a bold idea known as the “signal hypothesis.” It suggested that each protein carries in its structure a sequence of signals comparable to address tags on airport luggage or ZIP codes on mail to ensure that it all arrives safely.

The signals, Blobel found, are chains of amino acids created by protein-making machines that read distinctive RNA codes and then fix them on each new batch. Like transmitters, these signals order receptors in membranes to open up watery holes so proteins can pass through. They then act as GPS devices to cross the crowded terrain of a cell or a human body and, like finding a mailbox across the universe, penetrate precisely the right worksite organelle for each protein’s assigned task.

Proteins have many tasks: rebuilding or replacing constantly dying cells, protecting against viruses and bacteria, regulating body chemistry, reading DNA to make new molecules, releasing hormones to signal and repair tissues and organs, carrying and binding atoms throughout the body, and many other functions.

Despite proteins’ variety and complexity, however, Blobel demonstrated that their signaling system for getting through barriers and finding their worksites is universal, operating similarly in all animals, plants and even common yeasts.

Moreover, he found, this signaling system has evidently been working quite smoothly for millions of years, since the evolution of the first cell. Mistakes can be catastrophic to an organism, but they are relatively rare.

“Günter Blobel’s discovery has had an immense impact on modern cell biological research,” the Nobel Assembly at the Karolinska Institute in Stockholm said in announcing the prize on Oct. 11, 1999. “Furthermore, knowledge about the topogenic signals has increased our understanding of many medically important mechanisms.”

Günter Blobel was born on May 21, 1936, in the Silesian village of Waltersdorf, then in eastern Germany and later part of Poland. He was one of eight children of Bruno and Margaret Blobel. His father was a veterinarian. The boy and his siblings attended local schools, and in their remote village the family, by his account, was bypassed by World War II until its closing months.

“Until then my childhood was a perfect 19th-century idyll,” he wrote in an autobiographical sketch for “Les Prix Nobel” (2000). “In the cold and snow-rich Silesian winters there were hourlong rides on Sundays in horse-drawn sleighs to my maternal grandparents’ farm to have lunch and spend the afternoons. The house was a magnificent 18th-century manor with a great hall that was decorated with hunting trophies.”

In late January 1945, the family fled in a car from the advancing Red Army, heading west to seek refuge with relatives in Saxony. Passing through Dresden, Günter, 8, was struck by indelible impressions of the city’s “many spires and the magnificent cupola of the Frauenkirche” (an 18th-century Lutheran church with one of the largest domes in Europe) and “the many palaces, happily decorated with cherubs and other symbols of the Baroque era.”

Days later, on Feb. 13, Blobel recalled: “We saw from a distance of about 30 kilometers a fire-lit, red night sky reflecting the raging firestorm that destroyed this great jewel of a city in one of the most catastrophic bombing attacks of World War II. It was a very sad and unforgettable day for me.”

As chaos engulfed the crumbling Third Reich, the family was split up among relatives in various villages. After the war, the Blobels settled in Freiberg, in Soviet-occupied East Germany. Günter graduated from high school there in 1954, but, refusing to join a communist youth group, he was labeled “a member of the capitalist classes” and barred from universities.

Crossing to West Germany, he studied medicine in Frankfurt, Kiel and Munich and earned his medical degree at the University of Tubingen in 1960. After two years as a hospital intern in Germany, he decided that medicine was merely treating symptoms and that to get at underlying causes he must devote himself to research.

At the time, his brother Hans was on the faculty of the University of Wisconsin on a Fulbright Scholarship. Hans urged him to move to Madison for advanced courses to enhance his chances for a career in medical research. Blobel did so, and earned a doctorate in oncology at Wisconsin in 1967.

He then joined the Rockefeller Institute for Medical Research as a postdoctoral fellow under Palade. He moved steadily up the ladder of Rockefeller University, as assistant professor of cell biology in 1969, associate professor in 1973 and full professor in 1976. Since 1992, he had held the John D. Rockefeller Jr. professorship. He wrote many scientific articles and never retired.

In 1976, he married Laura Maioglio, the owner of Barbetta, a Manhattan theater-district restaurant founded by her family in 1906. The couple, who had no children, kept homes in Manhattan and Fubine, Italy.

He is survived by his wife; three brothers, Hans, Reiner and Albrecht; and two sisters, Sigrid Mack and Ingeborg Cosack. Tall, gentle and white-haired, Blobel, who became a naturalized American around 1980, won a score of awards, including the 1987 Horowitz Prize for biochemistry from Columbia University and the Albert Lasker Medical Research Award in 1993 for public service. Both cited his work on cellular proteins, and explicitly noted the ZIP code analogy mentioned in his later Nobel citation.

After winning the prize, he told Medical Tribune, a publication for doctors, that his work would lead to medical and pharmaceutical innovations in treating leukemia, schizophrenia, AIDS, cystic fibrosis and many other conditions. “It will impact on every disease, essentially, because all diseases have a molecular-cellular basis,” he said.

Blobel donated the Nobel’s $960,000 stipend to Friends of Dresden, a group he founded in 1994 to help restore the city’s architectural legacy, particularly the Frauenkirche, which was lost in the Allied bombing, and a synagogue to replace one destroyed by the Nazis in 1938.

The gifts were made in memory of his sister, Ruth, who at 19 was killed in an air raid near the end of the war.