Attacking The Roots Of Cancer
Israeli Nobel winner, at 74, still researching why cells go awry.
Staff Writer
Avram Hershko
Avram Hershko

Dr. Avram Hershko, a Hungarian-born Israeli biochemist, shared the 2004 Nobel Prize for Chemistry with his former graduate student, Aaron Ciechanover, and American researcher Irwin Rose.

They were recognized for their joint discovery of the ubiquitin system, the mechanism by which cells of most living organisms degrade and discard proteins that malfunction, leading to diseases such as cancer.
Hershko earned medical and doctoral degrees from the Hebrew University-Hadassah Medical School in Jerusalem in 1965 and 1969, respectively, and joined the faculty of the Technion-Israel Institute of Technology in Haifa in 1971. In 1998, he was appointed a distinguished professor, allowing him to continue working beyond the university’s mandatory retirement age. He is one of 76 cancer researchers in Israel who received grants this year totaling more than $2.7 million from the Israel Cancer Research Fund, the largest private funding source in Israel for cancer research.

Jewish Week: I understand that since you won the Nobel Prize you have continued to try to better understand the ubiquitin system. What specifically are you looking for?
Avram Hershko: The ubiquitin system destroys proteins that carry out all the processes in our body. DNA is the genetic material that functions to make proteins, and each gene makes one protein. The gene is like the conductor of an orchestra and the proteins are the players. It’s a big orchestra with thousands of players, and they have to play in harmony and be coordinated.
The role of the ubiquitin system I discovered is to destroy proteins that can no longer work properly. So in a symphony if a cello is playing when it is not supposed to, the ubiquitin system comes in and destroys the cello.
The ubiquitin system is important also in cell division, and here we come to cancer. Cancer is cell division that should not occur. In cancer patients the ubiquitin system does not destroy the proteins that make cells divide.
My discovery was basic science trying to understand why proteins died — how they were disposed of. This basic discovery led to the creation of a new drug, Velcade, that is targeted against the ubiquitin system and is helpful in the treatment of multiple myeloma, which is bone marrow cancer.

There are scores of different types of cancers. Are there any similarities?
They have a common denominator — cells dividing when they should not divide. In addition, we have DNA within our chromosomes, and normally when a cell divides each new cell gets the exact same number of chromosomes. The human cell has 46, and when they divide you get 46 new chromosomes. In a patient with cancer, each new cell gets a different number of chromosomes. So there is chaos, and that is important in the progression of cancer because it gets worse over time.
The ubiquitin system is involved in maintaining the accuracy of chromosome splitting so that they divide properly. I am now trying to understand how the ubiquitin system controls the accurate division of chromosomes — and that is important in cancer. Hopefully we can get some insight to be able to treat different kinds of cancer because when cancers get worse, the number of chromosomes goes crazy. Hopefully we will be able to stop this type of cancer.

It is said that finding a cure for cancer is unrealistic because there are so many different cancers. Is that correct?
That’s true, but if it can stop the progression of cancer, if we can give patients a good quality of life for several years — that is the aim. Then we have accomplished something. But we are not there yet. What I’m trying to do is understand the ubiquitin system. Then we would be ripe for getting there. I have been working on this for the last seven or eight years, and I am about half way to understanding it. It’s a long process but you have to start.

How much longer do you plan to work?
I’m 74 and I’m planning to work much more. I don’t feel my age; I’m making plans to work more than 10 more years.
I began working on the ubiquitin system about 30 years ago and ICRF has provided me with much of my funding for the decade or so.

Is cancer research getting enough funding?
It is never enough. I don’t have grudges against any funding agency — there are other priorities — but attention should be given to basic research, not just applied research.

Basic research has to be supported by society. Although it is not giving any direct benefits, there must be a long-range investment by society because all basic discoveries are eventually used for important applications.