Good Morning Aaron. Good Morning, Avy. Thank you for coming and your willingness to share your experience with our students. I want to start with the biggest question. We tend to classify new product developments on a spectrum between minor modifications and breakthrough thinking. And I guess that your invention was a breakthrough thinking. Am I right? First of all, it's not an invention. It's a discovery. We discovered the system that has been there for millions of years. So, yes, when we discovered it, we didn't know that it's a breakthrough. And it became a breakthrough only later on when the importance was unraveled and then later on when drugs were developed based on need that have now saved the lives of millions of people worldwide. So the importance was gained a long time. We couldn't predict it at the very beginning. What was the driving force behind your research? The driving force was curiosity, and we had to define a question for ourselves for the system that we didn't know much about or didn't exist at that time or wasn't in the knowledge of the people. And it turned out to be what many people thought at that time were very neglected, unimportant problem, and that's how proteins in the body are destroyed. People typically are interested in construction, in build-up. And we were interested in waste, in garbaging of protein, and garbaging is never something that is exciting or interesting. But we nevertheless thought that there is something interesting there, and we decided against the stream and against the thinking at that time in the field to go there and the rest is history. Was it difficult to swim against the current, where everybody was thinking differently? It's very difficult to swim against the current because, first of all, you are taking a risk. You don't know where you may end up drowning in the swamp of nothing. And so it will be the end of your career. You may spend years and years searching for something elusive that either doesn't exist or truly is not important. That's one risk but, the other risk and the other difficulty is practical. Publishing in science, you need to publish in order to not only to be promoted, I think that promotion is something secondary, but in order to bring the system that you discovered to the attention of the scientific community so other people will pick it up. So people are very skeptical about it. They don't believe that it's important. Then you'll encounter problems in publication. Obviously, if you cannot publish, you are encountering problems in funding. Funding is a very important element in basic research. So it's a vicious circle that accelerates itself. And it takes time to get out of this vicious circle to the point when you are recognized that there is something. You are never recognized immediately as a breakthrough discoverer, but there is a point that people say, "Yes. There is something about it," and then you start to emerge gradually out of the darkness. Many breakthrough discoveries are the foundation for new products, new markets, new inventions. Was it the case in your? Well, I'm a physician by my education, and I'm coming from the world of life sciences and biomedicine. So there, the implications are clear because if you're doing research and you're discovering a system that is working in the human body or even in the body of other organisms, and there is always an application, a possible, a potential application in the horizon, in the form of either a device to diagnose diseases or a drug to treat diseases. Anything that has to do with human health, improving human life and so on and so forth since we discovered the biological systems that treasures the protein.Then, obviously, aberrations in the system may lead to accumulation of garbage proteins in the body. Think about strike of the garbage collector in our city. First day, you can tolerate. Second day, smell will come up in the air. Third day, the cats and the rats will come around. Fourth day, people will be hospitalized because of infectious diseases. The same happens in the body. So we didn't predict it. We really were driven by curiosity and by the fact that the answer to the question was not known. But since, again, we are dealing with a human body, people immediately once the system became known, and people realized that it's important. People discovered that there are diseases, where the body with the system is aberrated, accumulates garbage proteins, disease and then the drug industry is walking on, and there is a huge drug industry around our discovery. So it was a staged stepwise process that evolved along two decades since the discovery was slow. Well, I don't know what's slow in science. But at the end of the day, there are wonderful products in the market, and we're just seeing the tip of the iceberg. But, again, we are driven by curiosity, and I think that that's the beauty of science. You're not the one that have to take the discovery all the way to the shelf in the supermarket or in the factory or wherever. You're doing one stage. Somebody else realized that it's important, model it, realize that indeed it has to do with diseases in our case, the pharma companies coming in. So it's a multi-bodies type of an effort that at the end matures to a very successful product. You talked about the risk involved in breakthrough discoveries. Is it a way to mitigate or to manage such risk, or you have to take it as it is, and you can do nothing about it? If you really want to make a real discovery, you have to take a risk. I'm an adventurist by nature, I've always been. So for me, it's a game. I like to walk on the very brink of the rock, and there were the risk of all the time crashing into the valley below. So, I'm a risk-taker by nature. And I think that you need to take a risk like in business in any other thing. I don't think that you have to be genius. It's not thinking out of the box. It's defining the problem knowing that there is indeed a true problem and then go into it. And then, I think that the risk as big as the reward. So you have these two sitting in front of you, and you know that you're going either to crush or to climb to the tip of Everest, and it's your choice. If you're taking the paved road, it's the paved road somebody has paved it, and somebody is already riding it, there is no surprises on the paved road. So, I think that you need to take a risk in science anywhere, in business anywhere. Can management develop a system where people will be willing to take risks or? Yes. Let's put it this way. We were not alone. I'm not taking any credit to myself. We were surrounded by excellent people, in this case, our co-share of the Nobel Prize. I was a graduate student as a matter of fact when I made the discovery. So, I had a very good mentor, and we were in a very good ecosystem at that time. I think that nowadays, the science has become very complex and multidisciplinary. We need computer scientists around here at least in my profession. You need chemist. You need physicists, device people, a data analyst and so on. And the management has a critical role usually in mitigating the risk. You can mitigate the risk. And one is to build the infrastructure, to invest in infrastructure. That's something that doesn't belong to a single researcher but serves the community. You know microscopes, genomics, proteomics, screening of molecules, that in the case of the drug industry, biomedicine. This is one thing. And the other thing the institute has to build around you in other parts of the ecosystem and that having excellent people that you can talk to around you, you need the critical mass. We are not alone anymore. Discoveries are not coming from the Louis Pasteur type of work that the single "crazy" scientist is sitting in his room or in his laboratory, and making an invention, and everything explodes out of the window, and the world bows in respect to this major discovery. It's always teams. There is a leader to the team who came with the idea but it's always teams and management is responsible for establishing such a team. It's not a team that works together in collaboration, but it's an environment by which you can get advice. I call it the noise of the corridors that you're walking out of your room, and there is always in the next room an expert, a good graduate student, a technology, an instrument, whatever that you need in order to solve the problem that just came up. Yes, the management plays an important role. How about teamwork? Do you need a leader to the team or the team can be just a collection of good people working together? You do need I think a leader, but I cannot tell you what will be in the future. Nowadays, I think that you still need a leader that will come with the idea and will glue the team together. People become eclectic. We shouldn't forget in science there is always an issue of credit, who is credited, and then people start to take their own way. You need the glue. You need the leader. You need a role model. And I think that people accept leadership. They accept leadership. So you do need somebody that will come with the idea, and somebody will find the resources, somebody that will convince the management that this is the right idea. In the case of business, somebody that will convince investors that the idea are worth pursuing and invest more and more. And in the drug industry, it's huge because, at the beginning, the investment is kind of, not minor but moderate. But once you are coming to the clinical trial and especially to the phase three clinical trials, we are talking hundreds of millions and billions of dollars. You do need to invest investors pharma companies to go for it and leadership is important. Is it possible to train such leaders to educate them? Can we as the university develop a system or a program by which we train new product development leaders or new scientists as leaders? I can't tell you because I can only judge from my own so-called success. I grew up. So maybe I'm a natural leader or maybe not. I don't know. But I think that yes. I think that the world of today is extremely professional and extremely multifaceted, multidisciplinary. Think about running a hospital. It's not enough to be a physician. You need to be understanding finances. You need to understand new technologies. You need to know the preference of the new technology. You can buy all the toys in the store, and then go bankrupt in no time. Preference, you need to understand the market, what the advantages that you have over your competitors. And I think that you do need to educate leaders or to give them some tools to run teams and so on and so forth. Yes, I think that this is an important part of our education, but at the end of the day, you do need the brilliant, courageous risk-taking people. So, it's a mixture of selecting the right people and giving them the right to education, the right training, the right tools and techniques and so on. From your experience, and I'm sure that you had many students in your lab, is it difficult to identify the future leaders? I find it difficult. Students are coming to my lab to something like six years to do their graduate studies, Ph.D. So, you try to use some tools. And some of the tools that I'm using is obviously their past. You're always build on a credit. So, if somebody was a good student in elementary school and a good student in high school, and excelled during the bachelor-ship and during the Master-ship, there is something to him, if it's a persistent success. But then, it still doesn't guarantee anything because people can be just hardworking and obedient and they will be shy from coming with their own ideas. They will not be able to challenge authority, to ask the right questions, to say, "No, my dear mentor. You are wrong. I read something." So it takes more than just excelling, and it takes just formally excelling by documents. And it takes time at the end I discover them along the way. But I think that in our world there is a place for people of all kinds. For team players that maybe not these leaders. And then for the very thin layer of people that will grow out of it, that will have all the attributes that are needed in order to come with them. And I've seen them all. I've seen them all. But I must tell you that the mixture that you are just talking about is rare a one. We are not walking in the streets for free and in large amounts. I agree with you. And the next question is if we agree that a good leader in your product development has to have this. Born talent. Let's call it charisma. The gift of God. And some tools that we can learn. What is the most important tool that we can teach? Well, I'm frequently asked about the secrets or the recipe for success. And admittedly, I must tell you that the real element is luck. But beyond luck, there are element that are in our control. I say luck because I tell people, if there was a real recipe, I wouldn't have told you it anyway because I would have used it myself to run for my second success. And the fact that there are now second successes, at least now in science or they are very rare, tells you that a lot of it is beyond our control. But nevertheless, you can control it. You can control it to some extent. I think that hard work is minimal element. Maybe in Mathematics you can be sparky, something comes to your mind. But in life sciences, in biomedicine, in business, you need to really be a time investor. So, a second element is passion. You need really to love what you do. People ask me from time to time about my profession. I said, I've never had a profession. I always had a hobby. And I'm very lucky to have a hobby because I'm coming everyday to my lab or to what I do. And it's like a new day for me and this new day is repeating itself for the last 40 years that I've been there. And it's wonderful to feel like that and even my university pays me for that. So, why not? Ideal life, somebody pays you for your hobby. So, passion, passion is extremely important. Otherwise, if you should just look at it as a source of your monthly salary, you'll never succeed. And another element is mentorship. I think that we talked about it. But mentorship, I was lucky to have excellent mentors almost all along my career from my school teachers, faculty of medicine, graduate school, post-doctoral fellowship, all along the steps of the ladder that I climbed along my academic career. So, mentorship is extremely important, and you see succession. When you see people, the Nobel Prize. You see that Nobel Prize educate another Nobel Prize, another Nobel Prize. So, mentorship is extremely role modeling. It's like apprenticeship. But in the apprenticeship, there are two sides, there is the teacher and the students. It's doesn't have to be active teaching by your mentor. That he will give you a list of instructions and you follow them one by one like a checklist. It's just you look at him and either you grasp it or you don't. It's like surgery, it's an art to hold the scalpel in the right way. And you look at your master, and it's like a master class, the old Middle Ages Renaissance time master class. So mentorship is important. We talked about ecosystem of the management. So I think that there is a collection of elements that must be there in order for you to succeed. And then, your DNA that you inherited from your mom and your dad. And the luck, the stars in the heaven. And there are many elements. Many are in our control, some are not. I want to go back to management. A very difficult problem is when to terminate a project. It's going on, we already invested time and money and so on, but it's leading nowhere. Should management intervene? Should there be a point where management say, "Hey, we want to stop it." Well, I think that in science, I encounter it a lot of course. Because we are starting a project and then it goes nowhere and you have to take a decision, you have already funding for it. You have to have a good gut feeling when it's the end. You have also career. For you, it's management and business. For me, it's career of my students and the future of people. So, you cannot just send the students and tell them work and work and work and hit your head against the wall, starting to realize that nothing will come out. So you'll need to put a stop to it. Part of it will occur by itself because if there is nothing coming up and there are no results, then there will be no publication. If there are no publication, there will be no funding. So, it's kind of a self ending like a servo-type of machine that will end itself. Because it's crazy, you're going to commit suicide if you're keeping on running this track. And a lot of gut feeling. Actually, it's happened to me more than it doesn't happen to me. We're doing it a lot. We start a student on an idea, and then the idea doesn't work, and then you come to a decision you need to. This is an important characteristic or attribute that the PI or principal investigator, or a businessman, or an investor must have. And I think that that's common to all worlds of what we are doing. It doesn't matter where you come from. A major tool in our profession is peer evaluation. We are trying to publish and our results are sent over to peers who are knowledgeable in the area and they have to decide. Is peer evaluation a good way to judge new product development? Well, there are tons of literature written on the pros and cons of peer evaluation. Peer evaluation, I think that it's the optimal I wouldn't say ideal system nevertheless, because it's balance. You're sending it to different peers, different countries, but it's also biased. Your peers are also the experts are competing with you, so there is vested interest. If it's in business, you may revealing your secrets despite the signing of all kinds of papers and so on. It's very difficult to have credit on ideas and then to materialize it in court fighting. I'm witnessing in many patent disputes that run in different courts in Israel and abroad. But it's never the same. There are many interests behind, competition, commercial competitions, scientific competition, and selection of their own reviewers. From time to time, I see reviews on my work that the reviewer doesn't have a clue of what is in the paper. What's right? What's going on there? And then you have to deal gently with the editor and so on and so forth. But at the end, I think it's a balance system. If you have good reviewers and they are balanced, and the handling editor in the middle, the mailman in the middle is open to see the problems, then I think it's a working system. You need to have input of opinions coming on, but you have to take it with a grain of salt. Industry is now adopting the idea of peer evaluation. They call it the stage gate approach, where you're going through a stage in the product development project and then you have a gate. And in the gate, you have to explain what had been done, what you're going to do in the future. And your peers will judge your progress and the probability of success in the future. There are quite a few people who are promoting this idea, but from what I know from academic life, it's quite dangerous because peer evaluation may be biased. So the question is, should it be applied to industry and how? I'm not coming from the industry world, so I cannot tell you. But I can tell you that you need to have some input I think at the end of the day. And if the experts are neutral, and they don't have a vested interest, and they are coming from different disciplines, and you have mixed critiques that are coming and looking at the product from marketing, from quality control, from need of the market, then you get a balanced view. I think that then it's desirable. At the end of the day, we are not the masters of knowledge, we are just coming with an idea. If there is anybody biased, it's the discoverer or the inventor because he's for sure sold for the idea. So I think that consulting around, in science it's mixed. It's either peer review in the case of paper. It's either scientific advisory board for an institute that evaluate the overall performance or the overall academic direction. And I think that there is a place for that in the industry as well. I didn't think about how to establish it, how to evaluate it, who will be the experts, can you find experts that don't have any vested interest direct or indirect? That's very difficult today. People are lecturing for money for some company and the company is always in the back of their mind. You never know the spouse has shares in the company. It can be so indirect that it will be very difficult to trace. And even maybe the reviewer himself is not aware that he's biased by some factor. But I think that at the end of the day, if it's done in a balanced way, it has a value. There is a lot of effort to identify the critical success factors in new product development. Critical? Critical success factors. So, if you are to come up with a single critical factor that influence success of such project, what is it? For me, as a basic scientist, it's almost impossible to answer. Because in my case or even in our case,that there is a big economical success, huge drugs, billions of dollars industry, then you say, "Wow! What's the problem? There is money in the bank for the company." As for me, there is also lives of people that we save. For me, as a physician, it's a huge value. But for me, knowledge itself has a value. People are being recognized for understanding the acceleration of earth or the expansion of earth. For me, understanding the universe in which we are living, even it's a pure knowledge that you know that will never be applied at least not in your generation or not even in the generation of my grandchildren, it still has a value. So I think that it really depends from which culture you're coming in order to evaluate what is a critical success. I think that this element should really belong more to the business side than to the pure science side. Because in pure science, we really want to better our lives, and that measured by product and by the success of products. And the success is not only money. There are many money-making products that have no value at all to our health. They're bought because of propaganda of advertisement, we know how the market is working. And some really have a value. But for me, knowledge itself, just understanding the universe, has also a great value. So I think that it really depends on the culture in which you were reared up. Thank you so much for sharing your knowledge with us. Thank you very much. Thank you.
