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 rogue proteins to defend itself from diseases like cancer.
Israelis Aaron Ciechanover and Avram Hershko and American Irwin Rose won for work in the 1980s that could help treat illnesses like leukemia and cystic fibrosis by identifying how the body "degrades" unwanted proteins.
"When the degradation does not work correctly, we fall ill. Cervical cancer and cystic fibrosis are two examples," said the Academy in its citation, adding that such knowledge "offers an opportunity to develop drugs against these diseases and others".
The scientists found that the unwanted proteins which could, for example, lead to errors in cell replication or genetic coding are "labelled" for destruction with a molecule called ubiquitin. It sends them to "waste disposal" units, called proteasomes, where they are chopped into small pieces.
"We are not a building that stays still, we are all the time exchanging our proteins, synthesising and destroying them," said an elated Ciechanover. "Some proteins get spoilt. 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 told Reuters that it had already "led to development of numerous drugs for degenerative diseases and malignancies that big pharmaceutical companies are busy working on".
One drug based on the research is the bone marrow cancer drug Velcade made by Millennium Pharmaceuticals.
Proteins build up all living things but cells constantly regenerate, divide and die, making their breakdown a vital process regulating a wide range of biological activity including preventing plants from self-pollinating - which would lead to their eventual extinction - and cell division in humans.
Errors in DNA genetic code replication can lead women to miscarry or cause Down's syndrome. Most malignant tumours have faulty DNA as a result of mistakes in cell division.
Protein breakdown's role in these processes "is absolutely fundamental. There is nothing in the cell that can work without some role of ubiquitin or its cousins," said molecular cell biologist John Mayer at Nottingham University medical school.
The laureates' research had "enormous" significance for understanding the human immune system and fighting diseases such as cancers and neurological illnesses, he said.
Ciechanover and Hungarian-born Hershko, both from the Technion in Haifa, Israel, and Rose from the University of California in Irvine, will share the 10 million Swedish crown ($1.36 million) prize. Ciechanover said it would be a welcome boost in income for the low-paid Israeli researchers - and for Israeli science.
"I have never thought of money, we earn very small salaries in Israel," he told Reuters. "It is more the honour for Israel, for myself, that a small country can make it."
The other Nobel science prizes this week have gone to David Gross, David Politzer and Frank Wilczek for Physics and Richard Axel and Linda Buck for Medicine - all from the United States.