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Professor Aaron Ciechanover of the Technion–Israel Institute of Technology in Haifa, winner of the 2004 Nobel Prize in Chemistry, talks about the ubiquitin system and how it helped to pioneer successful cancer treatment. Discover how drug companies decide which kinds of research are most promising. How does Professor Ciechanover help children to fulfill their dreams of building a better world, and why does he see his work as a labor of love rather than simply as a job?
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Interview with Aaron Ciechanover
Israeli technology and knowhow is in the forefront of the war on cancer. Nobel Prize winner Professor Aaron Ciechanover talks about his research into the ubiquitin system, which has led to many breakthroughs in cancer research. Find out what the future holds for scientific research in Israel.
Douglas Goldstein: I am happy to have on the show Professor Aaron Ciechanover, who was born in Haifa. He is now a distinguished research professor in the Technion in Haifa. In 2004, he won the Nobel Prize in Chemistry.
Professor Ciechanover, you won the Nobel Prize for research into the ubiquitin system, which has actually led to major breakthroughs in cancer research. Could you give us a little background on that?
Aaron Ciechanover: I call the system that I discovered when I was a graduate student, along with my mentor Avram Hershko, "the garbage-collecting car" of the body. There are so many proteins that we don't need any more. Either they completed their function, or they are mutated, inactivated, or misfolded, and they need to be removed. We discovered the system in the body that removes them. Meanwhile, it was also discovered that the system plays many other functions. But you can imagine that if you have proteins that precipitate Alzheimer's Disease in the brain, for example, obviously you want to remove them, or if you have a mutated protein that causes cancer, you want to remove it. Aberrations in the system do indeed lead to different diseases, and accordingly many companies have walked in, and sever al drugs have been developed, while many, many, many more are in the pipeline. So it was basic science or a basic research discovery, but it has quite immediate implications for biomedical research and drug development.
Douglas Goldstein: Tell me about some of the companies that walked in. It's interesting you bring that up, because obviously the type of research you were doing would seem to be an obvious place for drug companies to want to sponsor development.
Aaron Ciechanover: I'm not involved with them at all. I'm purely a researcher in the Technion, but the first one was a Boston-based company, Millennium, that then licensed the product to Johnson and Johnson, and then to the big Japanese mega company, Takeda. But now, basically all the big pharma are in. It's a big movement now, and there was a big explosion in the field. I just read yesterday that Roche is going to invest close to a billion dollars in the development of drugs that are related to the system that we discovered, so it's just starting, but it's big.
Douglas Goldstein: How can the drug companies identify which new research is the most promising, because certainly if you look in Israel and around the world, there are a lot of great teams working, even if we just start to focus on the cancer issue? How do they know which ones are going to succeed?
Aaron Ciechanover: First of all, many companies do not succeed. Actually, most of the ideas are flushed down the sink at the very end, but the system that we discovered is a platform. It's not just a single protein, but close to 2000 proteins. I think that this is the natural way that science is going. You know, you struggle with an idea, you identify a problem in biology that still needs an answer, and then you go to basic research. Then people say that the basic discovery they just came out with may be involved in pathogenesis and the generation of disease. Then they show that indeed in animal models, aberrations in the system lead to diseases, and then the pharma company walks in. Many have failed, and some are successful, but it's the natural route of science. We are moving slowly, from basic to modelling, to diseases, to drug development. That has been the history of science ever since.
Douglas Goldstein: And do you think that the decisions are made at the university level where to start the research, or it comes from the other side?
Aaron Ciechanover: No, the decisions are made by the company of whether to go in, and they have a radar system that they scan different discoveries. They look for the maturity, and from time to time they buy early ideas from the universities. In our case, we have nothing to do with the drug development. We remain basic scientists. Maybe my university laments that they were foolish enough not to pick it up and to patent it, but I don't regret it.
Companies are looking at it, and from time to time it will be the big companies, from time to time it will be start-up companies, from time to time it will be people within the universities, or the research itself that will start it. There are many ways to start it: angels, venture capital, and so on and so forth. In our case, it was a big company in Boston that decided to look into it. There are a lot of serendipitous elements in the success. Like everything, you need a lot of luck. In this case, it turned out to be a big success story.
Douglas Goldstein: Now you mentioned the word before about start-up, and Israel is often referred to as a start-up nation. That phrase actually started quite a while ago. Do you feel that is still true when you look at the scientific community here?
Aaron Ciechanover: Yeah, maybe, but being a start-up is not good enough, because people are quick to exit. They sell their company for whatever, and then either they, or the government, or both of them don't have the patience to develop into mega companies. So very few mega companies have evolved in Israel. Maybe one of them is TEVA, but there is not a second TEVA in Israel, and I think that we are losing a lot of opportunities. We are selling for cheap, good ideas and other companies probably will cash it in. So we are a start-up, but we are not continuing up, or end up, or whatever you want to call it. So you may look at the book, at this bestseller, from different points of view.
Douglas Goldstein: Do you think that's something that we should be trying to change, or maybe the niche of Israel is to be the start-up, and then to sell it off, because we are simply not capable of developing?
Aaron Ciechanover: The more you develop, you increase the value of your invention, and you can sell it for more. Obviously the country, the people, the universities that patent, and the IP of the researchers have an interest to take ideas and to advance them as far as they can. Why sell it early? Israel is doing things towards this. The Weizmann Institute is now developing a big platform that will help researchers to advance their ideas. I hope that the chief economist of the ministry of economics will be thinking about it, and make developments to do it. Start-up is not good enough. It's good but it's not good enough.
Douglas Goldstein: One of the areas that I think is hampering a lot of development of the Israeli economy, or at least they talk about wanting to slow down Israeli growth, is the BDS movement. This is very popular on college campuses around the world. Have you felt any of that? Has there been any of that?
Aaron Ciechanover: I didn't, but it exists, and it's both hypocritical and stupid. It is hypocritical because even if you think that Israel is as bad as we may be, or may have thought that we are, we are not the culprits of the area. Look at what's going on around us. It's just awful, so this is hypocritical and stupid because we are bringing knowledge to the world. Actually, personally, I was attacked in one of my lectures, not by BDS. The lecture was scientific, and somebody asked me about Palestinian rights.
I said, "The drugs that were developed based on our discovery don't have any gender, religious, national, language, or any other label. It doesn't say 'for Jews,' or 'only for Israelis,' or 'only for good people.' It's a drug, and I'm sure that in your country, people are using it for the good, and I'm happy about it." That's what I answered. Science is to serve the world, and to serve humankind, and to better human life, wherever they are. Israel has contributed immensely to the world, and to boycott us is just stupid, but we should fight them with all our power.
Douglas Goldstein: If you are talking to younger people, high school students who are looking for direction in the sciences, boys and girls, what would you suggest?
Aaron Ciechanover: Now it is 8:30 in the evening, and tomorrow at 8:30 in the morning I am going to talk to kids in Zichron Yaakov. I do this a lot, at least once a week, and I try first of all to tell them that I'm not talking about Nobel Prize. I'm telling them about achievement, that we don't have a right to walk 80 years or 90 years on the face of the earth without contributing. We should do something, and it doesn't matter whether it's in science, architecture, or being a good teacher, or serving the community. That's the idea - you should contribute. About science, of course, I'm a physician and I am a scientist, and I try to excite them about the secrets of nature, how fascinating it is to play chess against God, against nature, or against whoever you believe in. It doesn't matter. It's just wonderful to unravel the secrets of nature, to peel it off like an onion, and there you are. The reward is obviously just the knowledge that you expose, but in my case it's not only the knowledge. It's also impacting the lives and the health of millions of people worldwide. There is no better reward than this one, and I try really to excite them and on top if it I'm telling them that it's in their hands. "Look at me," I tell them. I'm an Israeli who was born in Israel, grew up like you, went to the scouts, high school, military service, cursing in Hebrew, Arabic, whatever, and going to the market on Friday to buy some things, food for Saturday, for Shabbat. So I tell them, "Look at me. I am exactly like you, and you can do it." Have an impact on society.
Douglas Goldstein: I think that's an important lesson for children in Israel and all over the world. A normal person who does normal work can make a huge impact on the world. How can people follow your current work and what's going on at the Technion with you?
Aaron Ciechanover: I am a scientist. I publish my stuff like all scientists, and we are continuing to work on the same system that we discovered, digging deeper and deeper. Now we are involved with cancer. We discovered a new protein that is a strong suppressor of tumors. It supresses tumors, and we are studying its mechanism of action. I have been a scientist for the last 40 years. I am excited by science. I have not been blinded by accolades, recognition or prizes, and I wake up every morning and go to work to my lab, and my profession is my hobby. That's the secret of my happiness and my success, I believe.