MONTREAL — Aaron Ciechanover was, by his own admission, on the road to juvenile delinquency.
“I already had a police file,” he recalled. Seems bathers at the beach in his native Haifa resented his swiping their thongs when they were in the water.
There were other strikes against him: he was orphaned when barely into his teens.
It would have been hard to imagine then that this mischievous boy would one day be a Nobel Prize winner in chemistry, Israel’s first, along with colleague Avram Hershko, in 2004, shared with the American Irwin Rose.
Ciechanover was in Montreal on April 7 to give the inaugural Andrew F. Holmes Dean of Medicine Lecture at McGill University, attended by leaders in research, education and health care from around the globe. They would have had to be tops in their field because Ciechanover’s subject is obscure to laypeople: “The Ubiquitin System and Intracellular Proteolysis.”
But this groundbreaking discovery in our understanding of something that can go wrong in the body possibly leading to cancer has had an impact on everyone.
The day before, Ciechanover met with local supporters of Technion Canada at the home of Viviane Amar to talk about his life and work. Ciechanover has been associated with the Technion – the Israel Institute of Technology in Haifa – since 1985 and is a professor of medicine.
He was still a student when he and Herhko identified the mechanism by which the body gets rid of unwanted proteins – specifically, the action of a molecule they called ubiquitin because the action is constant. This molecule fastens to a protein, signals that it is to be destroyed, and accompanies it to a kind of cellular waste-disposal unit.
Ciechanover draws a parallel between the arc of his life and the development of the State of Israel.
He was born in 1947 into a family of modest means six months before the end of the British Mandate when war was just around the corner. He remembers food was scarce and staples were rationed.
His father, a law clerk, and his mother, an English teacher, died when he was, respectively, nine and 13 years old.
His only sibling was a brother Joseph, 14 years his senior, who became a surrogate parent. Ciechanover credits him with setting him on the path to success by encouraging him to be serious about his studies.
At 18 he was accepted into the only medical school in the country at the Hebrew University, simultaneously serving in the military. There were 25 candidates for every spot and competition was fierce.
Just as he graduated in 1973, the Yom Kippur War broke out. He served as a surgeon in the navy, tending to the massive casualties and spending months at a time at sea, including circumnavigating the African continent because the Suez Canal was closed.
After the war, he spent six months as a surgeon at Rambam Hospital, and soon decided it was not for him and that he wanted to go into research. “People thought I was cuckoo,” he said.
He met Hershko, just back from a post-doctoral fellowship in the United States, who predicted basic research could yield amazing new knowledge of protein.
They swam against the current, not looking into protein’s building properties but how it was destroyed. “After a year or two I realized we were onto something novel, but I did not realize how important it was,” he said.
“Everybody is interested in construction, how things are made. The attitude to destruction is that it is something you need to do, but it’s garbage. It was the same in science. People were interested in the genetic code, what makes us what we are.”
Israel was still a struggling country, and resources were limited. There was little interest in funding such unglamourous research whose goal was vague.
So, all the work that went into the discovery was accomplished in a lab, with rabbits.
“It was very primitive. If I say we spent maybe $20,000, I would really be exaggerating,” he said.
They asked themselves how it is that human tissue does not rot even though body temperature is constantly at 37 degrees Celsius, if not higher. “There had to be a mechanism to clean out proteins that are no longer useful. Every living organism needs a garbage-collecting system to take away proteins before they spoil,” Ciechanover said.
As long as this quality control system runs smoothly, the body stays healthy. If it goes awry, cancer may develop.
Ciechanover believes a faulty ubiquitin system is also implicated in all brain disorders and inflammatory diseases.
Ciechanover spent three years at MIT, was tempted to stay in the United States and had many tempting offers. His wife wanted to return to Israel, and so they did in 1985.
Winning a Nobel has not made him wealthy but has filled the coffers of pharmaceutical companies.
The discovery of ubiquitin led to the development of Velcade, a drug used to treat multiple myeloma, a form of leukemia, and others.
“Sales are $3 billion a year, but we get nothing. We were foolish business people. Nothing was protected. Everything was in the public domain,” he said.
Ciechanover has become a public personality himself. He is currently president of the Israeli Cancer Society and of the Israeli ALS Society.
“At least once a week, I speak in schools from kindergarten to high school, and to the teachers. I’m a big believer in education. I believe it is the best drug for peace and quality of life.”
Ciechanover, who oversees a lab of 20 researchers today, said he is still passionate about his work. “After 40 years, every day is like a new day.”