By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)
From developing new paradigms for early-stage drug discovery for rare and common diseases to fostering the convergence of peptide nanotechnology, and launching scientific experiments in space, Israeli biochemist Ehud Gazit is wearing many hats these days.
In his role as academic director at the newly-formed Blavatnik Center for Drug Discovery (BCDD) at Tel Aviv University in Israel, Gazit is leading efforts to provide the missing link that may enable many scientific discoveries to evolve into beneficial drugs. The Center is uniquely dedicated to translational science by helping researchers turn their discoveries into effective pharmaceuticals.
Gazit – also a biophysicist and nanotechnologist – stays active in his university lab, which explores biological and bio-inspired molecular self-assembly. The lab studies the organization of biological systems in diverse fields, including amyloid diseases, diabetes, virology, and metabolic disorders.
Gazit – who has been a faculty member at Tel Aviv University since 2000, after completing his postdoctoral studies at MIT – also serves as the Chair for Biotechnology of Neurodegenerative Diseases at Tel Aviv University, and heads the Laura Schwartz-Kipp Institute for Biotechnology.
Today, he is also leveraging his former role as the Chief Scientist of the Israeli Ministry of Science and Technology, as well as leadership positions at Tel Aviv University, to bridge science, government, and industry for the greater good of the community.
I recently had an engaging conversation with Gazit, who explained further the mission of the BCDD, his role as a public servant, and how a combination of out-of-the-box-thinking and ‘hutzpah’ can advance science.
Rich Soll: To set the stage, let’s talk a little bit about Israel. The country has several million people and is highly entrepreneurial, highly educated, highly motivated, with professionals in the life sciences and biomedical sciences, and is producing some of the world’s most cutting edge science and innovative products, which was captured a number of years ago in the book, The Start-Up Nation. In your view, what are some of the top factors that contribute to this disproportionate influence by Israel in the sciences and biomedical research?
Ehud Gazit: I think there are some things that are quite unique that may signify the way that Israel is seen. First, I think it’s out-of-the-box thinking – this is something in Israel that is very clear. Some of it is due to lack of resources. I remember during my time at MIT, I took these courses on out-of-the-box thinking, and then I realized that maybe Israel needed in-the-box thinking; out-of-the-box thinking comes very natural here.
Secondly, something that may be related to this is the informality which allows Israelis, many time young students and young faculty members, to challenge many of the paradigms. In order to achieve innovation, you need this courage, the hutzpah, to allow yourself to challenge well-known paradigms.
Thirdly, I think it’s the excellent public education system. In Israel, me and most of my graduate students, and my fellow faculty members, we are all products of an excellent public education system, especially the higher education. On a modest budget, we’re able to give first-rate education open to everybody independent of the socio-economic background. This is how you get the most out of the population. I think that every child, even if they grow up in a less favorable environment, deserves and can enjoy a high level education and get into a university – for about $2,000 a year, you get a first-rate education.
Rich Soll: Does having limited resources breed a new way of thinking because you’re faced with this unique challenge?
Ehud Gazit: Yes, you need to be very focused; you need to be very creative. When the resources are limited, indeed, you need to try harder, you need to be focused, and you need to know where you are going. It’s less of a fishing expedition, but rather very directed and precise science.
Rich Soll: Despite having all those limited resources, look at what you’ve done. And your work has such practical consumer implications, such as self-assembly as it relates to fast cell phone charging applications. Can you give us some other examples of this type of work?
Ehud Gazit: We applied a systematic reductionist approach to identify the most fundamental recognition modules in nature. This work had inspired hundreds of groups around the globe to follow our discoveries. Although our quest was for basic biological questions, it turned out to be very important also technologically as some of the minimalistic assembly units form nanostructures with unique mechanical, optical, piezoelectric, pyroelectric and semi-conductive properties. Scientists are very creative in using the nanostructures that we had identified. I have this Google alert on ‘diphenylalanine,’ the module reported in our 2003 Science paper, and every week I get all kinds of applications you couldn’t even think about. This includes the fueling of nano-boats, production of electricity by pressure or heating, and the use of the optical properties to measure very low temperatures like near absolute zero.
Rich Soll: Can you elaborate on some of the themes that you’re examining and the implications of your findings?
Ehud Gazit: We are working on diverse disciplines. One may think that it doesn’t make sense working simultaneously on energy storage devices, superhydrophobic surfaces, biosensors, biomaterials, disease mechanism and drug discovery, but actually they all have a common denominator, which is our quest to understand the most fundamental modules that mediate and facilitate molecular self-assembly at the nano- and micro-scales. I call our research minimalistic and systematic, not biased, so we take complex questions, let’s say recognition by proteins or nucleic acids or other organic molecules, and we try to cut it into the smallest pieces that allow the molecular recognition and self-assembly. It provides us with insights to mechanisms of disease. It helps us to understand how you obtain interesting physical phenomena by identifying these elements. We understand fundamentals of supramolecular polymers chemistry.
One of the things we study is the assembly of structures using the guanine, those parts of DNA and RNA that allow the recognition between the bases. By a systematic, minimalistic, non-biased approach, we go into guanine, which is one of the four nucleobases of DNA, but it is also being extensively used in nature. Evolution has realized over and over again the unique physical properties of guanine assembly. Guanine is the structure that allows the physical coloring of fish, allows chameleons to change their color rapidly, and it serves as reflectors in nocturnal reptiles like crocodiles. We use guanine-based building blocks to obtain various architectures at the nano-scale with remarkable and tunable optical properties.
Rich Soll: I read recently that you were involved in some space rocket experiments. Can you tell us more about that?
Ehud Gazit: Yes, it’s part of our collaboration with Space Pharma, an Israeli start-up company looking to explore biological activities in space, on the conditions of no gravity. We sent a system based on our small dipeptide system I mentioned and we are trying to see what will be the effect of no gravity on the substance that we put on the physical properties. I do hope that we will see alternative architectures and new physical properties at zero-gravitation conditions.
Rich Soll: This is outstanding science. Have new tools and knowledge increased the possibilities and functions of self-assembly?
Ehud Gazit: Yes, one emerging area is the ability of metabolites to self-assemble. It’s been realized for many years that metabolites can crystalize. This is a case of gout, kidney stones, but now we have new tools to understand the formation of the structures, to understand how alternative amyloid-like structures could be formed within the metabolite, and maybe provide new direction to disassemble these structures. We provide new insights into the mechanism of inborn error of metabolism disorders in which there is accumulation of metabolites. So I think, over the last two decades, there has been an important realization from the scientific and medical community of the role of protein self-assembly in neurodegenerative disorders. But I think it’s much wider, looking at molecular self-assembly in general, metabolites, proteins, and lipids.
Rich Soll: So let’s talk more about BCDD. How did it get started and what is its mission?
Ehud Gazit: We’ve been provided with a very generous donation from Len Blavatnik, who is a great supporter of science. Through my experience as a researcher, and as an administrator at a university involved in tech transfer, it became apparent that what is missing in Israel is the very early stage of drug discovery. By engaging in an inclusive, multi-disciplinary environment, we target not only the researchers who are familiar with drug discovery and development, but many others who are excellent scientists but discovered a new biochemical agent, a new receptor, or a new enzyme, but are not familiar with the first steps that could allow these wonderful discoveries to be translated to the development of drugs. In a recent call, we had nearly 30 applications from different fields.
The center is also open to other communities. We often host high school students, very gifted ones, who are being exposed to activities in drug discovery. We also provide information and testing for individuals with rare disease. We are looking for targeted therapy; we try to understand the basic mechanisms of rare disease, and we are in constant dialogue with patient organizations and others. Another activity of the center is organizing conferences. We have had conferences on rare disease, on computer-aided drug design, and drug discovery. We are having another annual meeting on drug discovery and development.
Rich Soll: By being a center, you can draw in research from the university. Is that working so far?
Ehud Gazit: Yes, we are able to include in the drug discovery community excellent researchers in the university who were not part of drug discovery and development activity. While Tel Aviv University is now doing remarkably well in terms of publications, we are ranked constantly somewhere between 15-to-20 in the world in terms of citations, and have many European Research Council (ERC) grants, even though the number of drug discovery programs is not high.
Through a collaborative approach, we can provide unique service and we can provide our own directions in terms of fragment-based drug development, natural products, and screening for individuals with rare disease. I really want the center to be involved particularly where we have some core expertise that is already appreciated by the industry.
Rich Soll: What do you see as the strengths of the center?
Ehud Gazit: Firstly, it is providing, under one roof in a very efficient way, the full direction needed for drug development beyond the screening, medicinal chemistry and computer-assisted drug design. For many of the projects we have an integrated approach. The center is turning excellent multi-disciplinary science into therapeutic leads. On a daily basis, we sit together – the computation scientists, the high through-put screening specialists, the biologists and the medicinal chemists – in the same room speaking about the challenges, discussing with the faculty members, and people coming from the industry what their needs are. It’s a truly integrative approach.
Secondly, we are located in the middle of the campus, the place for people to stop on their way to their lab, and for students to come by. We are just above the central lecture hall of the university so we have many times students, even freshman, coming to the center to learn about the importance of drug discovery and wanting to be part of this activity.
Thirdly, it is our understanding that you need to provide the full spectrum from basic science to applied science.
Rich Soll: Are there similar centers in Israel? How would you differentiate BCDD versus others?
Ehud Gazit: In Israel there is the National Center for Personalized Medicine at the Weizmann Institute of Science, which provides excellent services, and which we have very good connections with. We see ourselves being more of a research institute and less of a service provider. We try to have our own uniqueness and direction. In our case, there is a stress on an interdisciplinary approach and a close connection to patients. Other centers are excellent and we are coordinating our efforts with them, all for the benefit of science and the benefit of patients.
Rich Soll: You’ve had a very illustrious career – a great educational background, terrific research, a strong publication record, and then on your career side, rising all the way up to the Chief Scientist of the Israeli Ministry of Sciences. Can you share your personal journey?
Ehud Gazit: Similar to statistical thermodynamics, these were random walks. I always knew I would be a scientist, but being chief scientist for the Ministry of Science, vice president for research, these things were not planned. As part of my career, I joined Tel Aviv University after my post-doc at MIT. I grew through the ranks, had tenure in two years and became a full professor in about six years. And then I got this offer a very short time after I joined the university, about seven years, to serve as the vice president of research. You cannot refuse such an offer. I decided, quite to the surprise of many people, to assume also administrative roles. I was vice president of research, and chairman of the technology transfer office, but always keeping my lab active. Then came the offer from the Minister of Science to serve as chief scientist. Again, I could not refuse the offer. It was a way to serve the scientific community; I saw myself as a civil servant.
Rich Soll: What were some of your accomplishments and what lessons did you learn from having these leadership roles?
Ehud Gazit: I learned that science is truly bi-partisan, and something you could get a consensus from left to right, and center. There is an appreciation of the role and importance of science. I also learned that you must motivate players, at the political level and the administration level; you need to motivate people and convince them you can make big changes. I’m not an engineer, but one of the things that I decided was missing in Israel is a type of funding program that is specifically targeted to engineering science. We found so many times that engineers were doing either applied science or very basic science, but less of what I would denoted as ‘engineering science.’ So we established this fund for engineering science.
One of the other things that I pushed forward was international and bilateral agreements between Israel and other countries. I realized that when you convince people about what you do and build up the right coalition, it’s not political, but rather based on the understanding of the importance of things that you think should make a difference. It was really quite an exciting time. Scientists are usually not exposed to government and parliament meetings and hearings. It makes you understand the importance on making science accessible to the general public. You need to let the people understand why they invest so heavily in scientific activities. It’s important to bring the message to the public.
Another thing for me that was very important was to have a public education system in Israel as open as possible to all parts of society, so we have research and development centers all across the country including several in the Arab sector that I specifically supported, as well as special programs for the advancement of women in science. For me, it was a great opportunity to serve the public at the largest extent.
Rich Soll: How are you implementing those lessons learned to the BCDD?
Ehud Gazit: One thing that I realized is the importance of bringing together people from different disciplines. The BCDD is much about inter-disciplinary, and proving the full spectrum, from basic science to applied science. We also decided to focus on several subjects and one of them is rare disease, in which I see as a remarkable importance from a scientific point of view, but also as a service to society. I see our interaction with the general public, from parents to children with rare disease, for people who carry a mutation and looking for a solution. It is very clear for us that it’s not only about science, but we are there for the people. So in our decision to focus on rare disease and rare disorders, our research is also related to our service to the community.
If I can summarize, you must have excellent basic science in order to have excellent applied science; you can’t take shortcuts. It’s the importance of integrating different disciplines, people from different backgrounds, and the service to the community.
Rich Soll: Looking to the future, what milestones would you like the center to achieve in the next two years?
Ehud Gazit: I hope that we will have several leads related to both common diseases and rare diseases that are less explored. This is a very challenging type of opportunity, since we can’t count on having a drug come from the center very soon, but if the number of researchers, faculty members, and graduate students are involved in drug discovery opportunities was doubled or tripled, that would be very important. And I’d like to extend our dialogue with Israeli start-ups in the biomed industry, which needs the help of the academic institutes. Of course, we are truly hoping to get therapeutic leads for various diseases, but we also want to increase the community related to drug discovery both at the university and at the national level.
Rich Soll: So five years from now, what do you think the center would like?
Ehud Gazit: I hope the center, even though it’s still in its infancy, will be a source of excellence for the Tel Aviv University community as well as the community in Israel, and maybe internationally. I hope that we could provide the scientific community with new paradigms for drug discovery with new methodologies on the development of drugs. I hope that in five years, drug discovery will be a strong point of Tel Aviv University.
Rich Soll: It’s a wonderful set of ambitions. What will it take to achieve these goals?
Ehud Gazit: I think the way to be successful is to be brave, to think big, and to think out-of-the-box. Scientific activity is twofold: on one hand it’s to be the best possible at the state-of-the-arts; you must think at the current state-of-the-art in science. At the same time, you always have to challenge the known. You have to say, ‘maybe it’s different, maybe I can do it in a different way.’ I try to do this at the center; it is challenging.
Rich Soll: What advice would you give to young scientists?
Ehud Gazit: You must ask the major questions, you must be as good as possible at the science that you do, but you still have to think, ‘maybe I could change things, maybe I could use a different type of mechanism.’ Maybe it’s something beyond what we see. To be a successful scientist you must be brave. You have to believe in what you do. You shouldn’t be disappointed with failure. You should be very happy when you’re experiment is running just as opposite as what you expected.