Professor Avram Hershko, Technion, Israel Institute of Technology, Haifa, Israel, won the Nobel Prize in Chemisty 2004 for the discovery of ubiquitin-mediated protein degradation together with Professors Aaron Ciechanover and Irwin Rose. They were the first Israelis to win the Nobel Prize in Chemistry.
Here, Professor Avram Hershko speaks with Dr. Vera Koester for ChemViews Magazine about how curiosity, choosing the right research, and persistence work as a general principle for success. He also discusses the importance of good science teachers that can arouse the fascination of future scientists.
What do you enjoy most about the Lindau Nobel Laureate Meeting?
I enjoy the talks, but mostly I come here for the interaction with the students. They are very bright and very interested. I like to talk to young people, as they are the future, whereas we are the past. I find the interaction very enjoyable and I hope it is also helpful for them.
You studied medicine, then you went to biochemistry, and then you received a Nobel Laureate for chemistry. What do you now regard to be your field?
What you do first leaves a mark on you. I have been in medical school for a long time teaching biochemistry. So I have strong feelings for what is important in medicine and human health and how biochemistry and chemistry can help human health. Of course, the boundaries are kind of blurred that is why the Nobel Committee awarded me the chemistry prize; biochemistry is basically chemistry in the human body.
How did you come up with the idea of looking at how cells die?
Well, it was coincidental, how things happened. As a medical student I had to learn a lot of basic sciences. That is how I got into science. I didn’t dream about being a scientist when I was young, I wanted to be a doctor. But then after my M.D., I did my Ph.D. in biochemistry and then post-doctoral research.
The hot topic at that time was protein synthesis: how proteins are synthesized, how the information from DNA is transformed to protein, and how that is being controlled. When I went to the place where I wanted to do my postdoc, there were already 25 other postdoctoral fellows and everyone was working on protein synthesis. I thought it was too crowded and so I asked my tutor if I could work on something else. He said why don’t you study the opposite: protein degradation. Not many people were in that area.
Why did you want to have a topic on which not so many people were working?
I think young scientists should not do what everybody else is doing. You should try to find your own subject or niche that you believe is important but that is not yet in the mainstream.
I thought like this intuitively at that time. Now, I know I made a good choice. So, I studied the opposite of what everybody else was studying. People were not interested in this area at that time. That is also good, because you don’t have to worry about competition.
But how did you know that would lead to success?
Well I didn’t know. You know success is never guaranteed in science. I thought the topic was important, I was persistent, obstinate if you want.
It took me quite a long time and the help of other people: you may have heard of Aaron Ciechanover, who was my student, actually, my graduate student. Together with him and also Irwin Rose, who I collaborated with during my sabbatical at Fox Chase Cancer Center in Philadelphia, USA, we found out how proteins are degraded; that they are being marked by another protein called ubiquitin. And then we worked out all the steps. It was just basic science, we didn’t think about applications. However, now this discovery turns out to be very important in medicine. There already exists a potent drug for a certain type of cancer and many companies are working on it. So I came from medicine, then out of curiosity got into basic science, but in the end it actually helps fix people.
Is there a recipe for success?
There is no recipe. I tell my story and students ask me, OK, so what should I do now? I can tell them the general principle, that is, choosing a subject that is important but not in the mainstream. That takes some judgment and some luck to find, but a lot of judgment. And they have to persist with it because usually it is not easy. So there is a general principle, but no recipe.
Was your motivation to help people?
No, my motivation was curiosity to understand how a process works; a process that is very important for the body because your body has to get rid of dead proteins and proteins that are not needed.
How did receiving the Nobel Prize affect your work?
A Nobel Prize can be very dangerous for your work. You can go from one meeting to another, and, if you want to carry on with research, you, of course, don’t just feel you want to continue with what you are doing, but you want to do something new. But if you do something completely new, then usually it doesn’t work. For example, even Crick who I think is maybe the greatest biologist of the 20th century thought, OK I have found out how DNA replicates, so I’ll now study the brain in relation to consciousness. He didn’t get anywhere and this has happened to other people, too.
I think if you make too great a change after receiving a Nobel Prize it can be very frustrating. So, what I did is I made a change and now we are working on how the ubiquitin system is involved in cell division and how our chromosomes accurately divide into the new cells. But I am still using the same technology because the ubiquitin system is involved. So, I went in a new direction but it is based on what I know. It is be a change, a completely new direction, but I hope it won’t be such a big change that I won’t achieve anything. I want to achieve something.
So you are still working?
Yes, I am still working, I have a group, a small research group – I never had a big one. And I like to do experiments with my own hands. I enjoy it and do it almost every day.
How do your students react when their boss works in the lab?
I usually go in in the morning and talk with my students and my postdocs and then I begin my experiments. They know they shouldn’t interfere. It works well, I do some very good experiments myself.
Was that a huge surprise when you received the Nobel Prize?
So, so. I got some other prizes before. The Albert Lasker award, which is the biggest prize in medicine in the USA, and some other awards. Usually people who win a Lasker award have about a 50 % chance of getting a Nobel Prize. So it wasn’t a complete surprise. The surprise was that it was in chemistry and not in medicine, but that’s OK, I’m not complaining, of course.
Israel has a lot of Nobel Laureates. Do you, within Israel, meet each other or do you meet at meetings like this one?
Usually I see the other Nobel Laureates here. Aaron Ciechanover, for example, who used to be my student, usually I see here. But this time he left yesterday and I only arrived yesterday, so I didn’t see him. But we meet up sometimes.
We also had a very nice occasion, involving chemistry actually: We have some small towns in the desert where they have never had chemistry teachers. So, a colleague at the Technion, who is a real chemist, organized for chemistry teachers to go there to teach. He made a kind of celebration of teaching chemistry in the desert and he invited all four Israeli Nobel Prize winners. It was really a miracle that all four could come.
Do you think that how we teach students is important?
This is very important. If you have a good and interesting teacher, children will love the subject. They can even like mathematics if they have a good teacher but if they have a bad mathematics teacher, they will hate it forever. The same is true for chemistry and all sciences. We have to show the children how fascinating it is, how important it is, and teach them well, in a way that arouses their curiosity, not just have them learn by heart all kinds of formulas and things like this.
Arousing their curiosity isn’t easy. It depends on the teachers – so maybe the teachers have to be taught or selected to be good teachers. That is important for the future of science. Those students that are really interested will go into science or will have a bigger chance to go into science, but those who hate chemistry at High School will never go on to study chemistry or biology at university.
So do you have any ideas on how we can also improve the general public’s perception of science?
We should, of course, communicate with the public because the public is important. The public pays for research so it has a right to know what we are doing with the tax money that the universities and institutions are getting. So we should tell them the importance of basic research. Also, they should know that applications are based on basic research. It is very important to support basic research even though the prime driver of basic research is curiosity. They should know that the curiosity of good scientists is very important and can eventually after many years benefit society.
That is how science progresses, and how technology progresses. You start with basic research then based on this research other people look into applications and then society is paid back. For example, I started out by trying to understand how proteins degrade and now maybe thousands of people with the specific cancer multiple myeloma are benefiting. With this disease people died within a year or two and now they can have many more years of good quality life. It is all based on curiosity and, of course, it took thirty years of work, but eventually we got there.
Do you think in the future we will be able to cure all kinds of cancer?
Well, cancer is not one disease. So there won’t be one magic cure for cancer. Each type of cancer is a different problem. It will take time, but, eventually, you never know, there have already been big steps forward. Some types of cancer are treatable, some types are curable, and some are not at all. Eventually, if we work hard, society supports us, and good young people go into science then maybe …
And the last question. What do you do when you are not in the lab?
Well, even before my work my priority is my family. I have six grandchildren. My second priority is science and then the third is gardening, again something I do with my hands.
Thank you very much for taking the time for the interview.
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Avram Hershko, born in Karcag, Hungary, on December 31, 1937, and studied medicine at the Hebrew University-Hadassah Medical School, Jerusalem, Israel, where he obtained his M.D. in 1965 and his Ph.D, which he carried out under the supervision of Jacob Mager, in 1969. From 1969–1971, he was a post-doctoral fellow with Gordon Tomkins at the Department of Biochemistry and Biophysics of the University of California, San Francisco, CA, USA. He returned to Israel in 1971, when he took up the position of Chairman of Biochemistry at the Rappaport Faculty of Medicine, Technion, Haifa, Israel. He is currently a Distinguished Professor at the Rappaport Faculty of Medicine.
Avram Hershko, Aaron Ciechanover and Avram Hershko became the first Israelis to win the Nobel Prize in Chemistry. They were recognized for the discovery of the Ubiquitin System, the body’s method of removing damaged proteins.
Selected Awards
- 2000, Albert Lasker Award for Basic Medical Research, jointly with Aaron Ciechanover and Alexander Varshavsky
- 2001, Wolf Prize in Medicine, Israel, jointly with Alexander Varshavsky
- 2003, Foreign Associate, National Academy of Sciences, USA
- 2004, Nobel Prize in Chemistry, jointly with Aaron Ciechanover and Irwin Rose
Selected Publications
- Roles of different pools of the mitotic checkpoint complex and the mechanisms of their disassembly,
Esther Eytan, Danielle Sitry-Shevah, Adar Teichner, Avram Hershko,
Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 10568–10573.
DOI: 10.1073/pnas.1308928110 - Role of phosphorylation of Cdc20 in p31comet-stimulated disassembly of the mitotic checkpoint complex,
Shirly Miniowitz-Shemtov, Esther Eytan, Dvora Ganoth, Danielle Sitry-Shevah, Elena Dumin, Avram Hershko,
Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 8056–8060.
DOI: 10.1073/pnas.1204081109 - Regulation of the action of early mitotic inhibitor 1 on the anaphase-promoting complex/cyclosome by cyclin-dependent kinases,
Yakir Moshe, Ortal Bar-On, Dvora Ganoth, Avram Hershko,
J. Biol. Chem. 2011, 286,16647–16657,
DOI: 10.1074/jbc.M111.223339
