October 10, 2004, Updated September 13, 2012

Professors Aaron Ciechanover, 57, (right) and Avram Hershko, 67, in their lab at the Technion-Israeli Institute in Haifa.Two Israelis and an American won the 2004 Nobel Prize for Chemistry on Wednesday for helping to understand how the human body gives the “kiss of death” to faulty proteins to defend itself from diseases like cancer.

Aaron Ciechanover, 57, Avram Hershko, 67 – the first Israelis to win the chemistry prize – and Irwin Rose, 78, were honored by the Royal Swedish Academy of Sciences for their work in the 1980s that discovered one of the cell’s most important cyclical processes, regulated protein degradation.

Ciechanover is director of the Rappaport Family Institute for Research in Medical Sciences at the Technion in Haifa, while Hershko, originally from Hungary, is a professor at the institute.

Their work, carried out in the early 1980s, shows how a molecule called ubiquitin attaches itself to the doomed protein and accompanies it “to the cells’ waste disposers,” the Royal Swedish Academy of Science said in a statement.

“When the degradation does not work correctly, we fall ill,” the academy said, but added that the knowledge of how the breakdown process works offers hope for the treatment of cervical cancer and cystic fibrosis, among other diseases.

More than 25 years ago, Hershko took a road less traveled in science and began studying how cells rid themselves of unwanted or damaged proteins. With the help of his colleagues, Hershko discovered the ubiquitin system and eventually determined that it impacts major physiological processes in the body.

Scientists now know that it is involved in regulating cell division, aids in controlling embryonic development, and helps maintain the immune system. It is implicated in a number of diseases as well, including cervical cancer caused by the human papilloma virus. Because it is involved in the body’s inflammatory response to invading microbes, it may also play a role in autoimmune diseases.

At a news conference in Hershko’s apartment in Haifa, the two Israelis said they hope their work will lead to advances in cancer treatment. One such drug, Velcade, is on the U.S. market, Ciechanover noted, and “there are many more in the pipeline.”

“It does not mean that a miracle drug to beat cancer is on the way, but I do believe there will be advances in the treatment of cancer based on our work. This I truly believe in,” said Hershko.

“We are not a building that stays still; we are constantly exchanging our proteins, synthesizing and destroying them,” said Ciechanover. “Some proteins get spoiled. We discovered the process by which the body exercises quality control.”

Lars Thelander of the Nobel Committee for Chemistry said the trio’s work was highly relevant for cancer research. Ciechanover said it had already “led to development of numerous drugs for degenerative diseases and malignancies that big pharmaceutical companies are busy working on.”

An Israeli company called Proteologics is developing an AIDS drug based on the research of the Nobel Prize winners. Proteologics plans to raise $9-10 million in the coming week from Israeli billionaire Morris Kahn and generic drug giant Teva Pharmaceuticals and existing investors. Investors say Proteologics ubiquitin-based AIDS treatment has a good chance, but the company has not yet even reached the stage of conducting animal trials. The current financing is slated to bring the company to that stage, and allow the investment of tens to hundreds of millions of dollars in drug development should the animal trials succeed.

Hershko and Ciechanover said they take pride in being the first Israelis to win Nobel prizes for science.

“We’re a small country… so we don’t have all the infrastructure that big laboratories have in the U.S. or in other places,” Hershko said.

The prize is “identified 100 percent with Israeli scientists (who) . . . have worked and lived in the country and will continue to live and to work in this country,” Ciechanover added.

As reported last month by ISRAEL21c, Hershko has spent every summer in Woods Hole, Massachusetts since 1991, leading an investigation into cell division in clams in a project dubbed ‘The Clam Project.’

The international team convened to pry open part of the clam genome by sequencing the surf clam’s active genes. The effort is the first step toward sequencing the entire clam genome, and its goal is to provide scientists with better knowledge of the clam’s active DNA. Such information is crucial to the study of the basic cellular processes involved in many diseases such as cancer, premature aging, and muscular dystrophy. The scientists plan to use the new genetic information to create molecular tools such as antibodies, and DNA and RNA probes.

Hershko and Ciechanover, began working on their research into the ubiquitin system in 1981 when Hershko oversaw Ciechanover’s doctoral thesis in science at the medical school of the Technion. In 2000, the two received the prestigious Albert Lasker Basic Medical Research Award in New York, together with Alexander Varshavsky of the California Institute of Technology.

Hershko was born in the small town of Karcag in Hungary in 1937. Twelve years later, he immigrated to Israel with his parents and siblings. In 1956, Hershko began studying medicine at the Hebrew University of Jerusalem’s medical school and from 1965-67 served as a physician in the army. In 1969, he was awarded a doctorate in biochemistry from the Hebrew University. That year, Hershko went to the University of California for post-doctoral research, and it was there that he began his seminal studies on the ubiquitin system.

In 1994, Hershko was awarded the Israel Prize and in 1998 he was appointed head of the Technion’s Rappaport Institute of Medical Research. Hershko was appointed a member of the Israel Academy of Sciences in 2000 and in 2003 was elected a member of the National Academy of Sciences of the United States. He also received the Wolf Prize for medicine in 2001.

Hershko is married with three sons and five grandchildren, whom he calls “my major achievements.”

“Avram Hershko’s discoveries over the past few decades have revolutionized our thinking about the central importance of the ways that cells break down their proteins,” said Dr. Ronald Goldman, a biology professor at Northwestern University in Chicago. “His findings, as well as those of his colleagues, have provided critically important insights into the physiology of both normal and diseased cells.”

Ciechanover was born in Haifa in 1947 to parents who immigrated here from Poland before World War II. His father, Yitzhak, was a lawyer and his mother, Bluma, an English teacher. He was orphaned at a young age and brought up by his Aunt Miriam and his eldest brother, Joseph, who became legal adviser to the Defense Ministry and director-general of the Foreign Ministry.

Ciechanover began studying medicine at the Hebrew University of Jerusalem in 1965 within the framework of his military service and from 1973-76 served as a combat physician and later in medical research. In 1970, he also began a master’s program in basic science at Hebrew University and between 1981 and 1984, did post-doctoral work at the Massachusetts Institute of Technology in Boston. Between 1994 and 2000, he headed the Technion’s Rappaport Institute for Medical Research. He was also awarded the Israel Prize for biology in 2003.

Previous Israeli Nobel Prize laureates were Shai Agnon (Literature, 1966); Menachem Begin (Peace – with Anwar Sadat, 1978); Yitzhak Rabin and Shimon Peres (Peace, with Yasser Arafat, 1994); and Daniel Kahanman (who is also an American, Economics, 2002).

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