 Hello everyone and welcome back to Conversations with Tyler. We are recording on Armenian Christmas Day with Nubar Afayan. He is founder and CEO of Flagship Pioneering, but these days perhaps best known as co-founder and chairman of the board of Moderna, which has produced one of the two best anti-COVID vaccines in the world. Nubar, welcome. Welcome. We station our awards in und. That's Merry Christmas in Armenian, and we celebrate this day as our Christmas. A very simple question to start. Which aspect of entrepreneurship is hardest to teach to other people? The fact that it is a combination of mindsets and beliefs as opposed to a birthright and connections. And how did you learn how to teach that? By putting myself in the shoes of the students and imagining what I would have wanted to know before I launched down a path of doing entrepreneurship in as professional as a way as I could fathom. Because I also think that generally the field believes that entrepreneurship is condemned to be a perpetual kind of improvisational unprofessional act. And I some 25 years ago decided that it would be much more productive if we could think about which aspects could be made more professional. And the first way to do that is to figure out that it's neither genetic nor somehow only about these kind of amorphous characteristics. Then hard work coming up with learning ways to do the kind of future backwards planning that we involve. And it turns out those things can be learned by both practice and by hearing about case examples and how people made decisions. Now at Flagship you have a string of successes of what? Over 40 companies that you have helped to create. Is that correct? Yes, in my case yes Flagship has a larger number than that probably closer to 100 now. Now how is creating a company as a co-creator a different skill than being either a VC who picks winners or doing all the work yourself in building the company? How would you best describe the nature of that skill that you and Flagship have? Well I should say that Flagship is itself an experiment in a new breed of company that conceives and creates and launches and develops companies. So a company that develops companies is not a traditional way one fathoms what a company does. Our products are effectively platforms that are embodied within companies. So in that regard if you think of the traditional startup methodology what one needs to do is to take a scientific breakthrough or an innovation typically in the life sciences that comes from academia managerial skills to both initiate and then grow and manage the growth up and then capital. If all three of those things come in together and coexist harmoniously and the product works and the pricing is right and the excuse is right then you get a gigantic overnight success. The likelihood of that happening before we get to the product and the pricing and the execution is very low because the sources of innovation the sources of talent and the source of the capital have a lot of let's say friction among them as to what they think should be done. Contrasted that to what Flagship set out to do which is to have the innovation capacity the human capacity to lead and the capital all as part of one entity one organization such that they are co-deployed in pursuit of something that is then for slightly more risky in the eyes of others because we can persist and we can cooperate because we all share one common objective and that is the success of that thing that we're creating. So creating a company having all three of those elements coming from the same source is a very different act than collecting and optimizing the pieces. It's been my experience I've done both obviously for the first 13 years of my life before 2000 of my professional life I did it the traditional way and since then we've been doing it this way. And which part of entrepreneurship biotech entrepreneurship in particular is hardest to scale so you don't have 792 companies right so something is stopping there from being more companies what's that scarce factor. It's a good question because usually the form of the question I get is what is limiting and why don't you do more and I'd say the simple answer to that right now for us is kind of not being forced to let's put it this way in other words if there was a need for us to create 20 companies a year instead of a six to eight that we do I believe the same methodology could do that and I believe that we would not scratch the surface of the possibilities of transformations that could be going on but you know we've been you know one of the things you do when you're exploring novelty in our case novelty of our life form if you will that is flagship as an entity is we've been pretty cautious and pretty humble about the notions that what we do can be scaled and could be replicated and can be effective regardless of scale and that is not something that we can easily kind of defend and so we've given it some time to ramp up but your question more specifically what's rate limiting it's usually about people more so than capital and innovation since we're sourcing a lot of capital both to start these things but also to scale them you know some roughly five billion of capital has gone into our collective activities over the last decade a little more than a decade of it just as we've wrapped up so and then on the innovation side our methodology by which we actually make inventions which is quite different than the way scientific innovations are usually made I don't think that that is limited in its potential there's far more white space out there than there is occupied adjacencies which is kind of what innovation today is usually focused on so long way of saying I think it's about people and it's people who on the one hand need to be kind of trained in this way of thinking about it and be willing to dedicate themselves to a pretty contrary and way of life when speed is of the essence as it was with the Moderna mRNA vaccine how do management styles have to differ well Moderna is a company that was already 10 years old by the time the virus appeared and so unfortunately for the virus there had been quite a lot of time to get ready with a platform and with a team that was assembled even though it was still a massive undertaking to do something that had never been done before so from a managerial standpoint it's a combination of being able to focus very rapidly on the task at hand be able to make rapid decisions which requires a level of pre alignment around how to do what we do around alignment around values and and and then execution with rapid iteration all of those things are crucial to to kind of perform at that type of uncertainty and that type of pace and fortunately in the Moderna case they had nine years of upbringing before the pandemic that was filled with that culture that those set of principles and so I think we were somewhat lucky in being poised to take on things that others would consider well first of all they all considered impossible but that was not new to Moderna because when Moderna as for the last 10 years heard that everything is doing is impossible and then improbable and then undesirable and then but now you know hopefully we've at least shown that in one case it can be effective and impactful and then that opens up a whole lot of new opportunities there's a now famous two-day origin story right so you don't even have a physical instance of the vaccine you just have the code and in two days you you come up with basically the relevant innovation now during those two days what are you doing are you peering over someone's shoulder are you at by the swimming pool are you on zoom calls all day how do those two days look for you you know actually for me my role as an eco founder and chairman has been to work with the leadership team obviously separate from the board itself on a variety of strategy issues that required very rapid decision making the decision to go down this path is one that involved more than just having a sequence in fact you know there was very little doubt in any of our minds that we could go from the sequence to a vaccine in a short period of time we've done it many many many times before it's just that that speed wasn't needed or appreciated by anybody didn't mean that we took three months before and now we did it in two days it always can be done pretty quickly that step but the decision making that proceeded it was were we willing to kind of gear up to go into the clinic in in a matter of weeks from having the starting point and and that was the thing that I was mostly working with Stefan and his senior leadership team on the scientific team that did the conversion of the sequence and optimization frankly did what they do for a living I should point out Tyler one of these people don't yet realize is that there are this is you know mRNA in addition to being unique in that it's really the first broadly applied code molecule information molecule that is used as a medicine and with all the advantages that come with information versus you know kind of digital versus analog or where you actually have to do everything bespoke the way drugs usually work the other major advantage that that it has is that it is something that is actually taking advantage of nature and so there was a lot of know how we had going into this around how the process could be done and in fact let me tell you the parallel that we used we have a program in cancer vaccines you might say what is a cancer vaccine have anything to do with coronavirus the answer is the way we work with cancer vaccines is that we take a patient's tumor sequence it obtain the information around all the different mutations in that tumor then design the novel completely nonexistent before set of peptides that contain those mutations make the mRNA for them and stick them into a lipid nanoparticle and give it back to that patient in a matter of weeks that is an ongoing has been ongoing for a couple of years clinical trial that we're doing well guess what for every one of those patients we're doing what we did for the virus over and over and over again so we get the RNA sequence we convert it into the antigenic part we make it into a RNA we put in a particle so in a in an interesting way we had interesting precedents that that allowed us to move pretty quickly that and the partnership we have with NIH where for the prior year and a half we've been actively working on a MERS vaccine which is a close cousin to the SARS-CoV-2 and therefore we had specific knowledge together with NIH the NIAID Dr. Fauci's group on the particular protein that we need to go after so all of those contributed to be notable very quickly why is it that right now it seems so many biotech successes are turning into reality they're not just cool articles in the Atlantic they're things that are working we're now stage three on a malaria vaccine CRISPR against sickle cell anemia why the sudden concentration is that computational techniques it's partly computational techniques for sure convergence as people call it between technology and biology I'm you know I've been working in that space for 33 years so it seems like an overnight success 33 years in the making in the sense of you know there was no human genome back then we didn't know even what proteins were existing in the body and we've come a long way we know things about you know hundreds of millions of bacterial sequences that occupy our gut we've learned that viruses occupy our body that we could use for therapy all these things it's it's kind of the expanded frontiers coupled with and this is what I would say at least that's where we come from the willingness and the ability to leap right so my belief is that we've reached a level of capital confidence commitment community whatever of those C start you know C letter starting words that it takes to get to a critical mass where people are willing to leap they're not just incrementally doing you know if a then be then be blind and then maybe see this sequential incremental and then looked at the permission to leave the permission to leave is given either by confidence or need if you have a pandemic you have permission in the need to leave if you have serious diseases that you can truly cure through editing or gene therapy you have an obligation and those things are all converging but yes absolutely capability those needs were there before now we have more and more capability but I'll tell you 10 years from now the capability we have will seem like 1% of the capability we will have I'm very sure of that 15 years from now how will CRISPR make people's lives better I don't know if CRISPR will be the particular technique that's used 15 years from now to be honest because I think CRISPR like many other things is a is a step along a series of innovations that will go beyond that and by that I mean the particulars of the enzymes that are bacterially derived that have been repurposed to edit one or two letters I think that the the next step beyond that will be and you could imagine we're already working on it we worked on CRISPR we were one of the founding groups that was involved in the formation of editas but we're now moving on to gene writing and and like basically literally inserting words and sentences into the genome not just spelling mistakes but if you think of CRISPR as a metaphoric CRISPR kind of the ability to to do things with a genome I think 15 years from now we will see multiple rare genetic conditions that are addressed by and corrected by it during somebody's life as opposed to in the conception phase which is which is a whole another ethical issue but I think that will be done it'll be more precise it'll be more pervasive but I think there'll be plenty of other ways to that will compete by the way with the end result which often is I need a corrected form of a protein I don't really care if I get it from my DNA being altered or I get a virus that can safely coexist with my cells so that keeps making what I need or RNA I mean you know one of the things that we got to realize is that in this field it's not winner-take-all at all it takes too long it takes too much money to kind of then say okay once I've done it I own the field it's different than the tech sector where the competition is around execution and then here I think there can be multiple approaches that can be taken forward and are being taken forward and they'll all exist when will the mRNA platform repair someone's damaged or bruised heart for instance look we have a program as you probably know that's in phase two trials with AstraZeneca that's going into phase three to work on post myocardial infarction a heart muscle recovery through stem cells it's using a molecule called VEGF that in animal studies and in phase one we've already shown indications of safety and potential for activity and we're advancing that with AstraZeneca I think those programs are probably several years two three four years in clinical development it's still going on because you've got to make sure you can show a treatment effect but I think especially now that the platform is even further blown out and established we'll be able to pursue not one of these but 10 20 of these and let's see which one makes progress more quickly as you well know some of the early papers on mRNA vaccines they were rejected repeatedly at academic journals Kotel and Kariko had trouble in her academic career now she's highly likely to win a Nobel Prize so what's wrong with academia and how do we fix it well I'll just say that is true generally you know in their particular case it was really more about pretty basic mRNA modifications as opposed to vaccines because back 20 years ago people weren't working on vaccines they were just working on being able to show that mRNA could even get into a human cell and people were quite resistant to believing that was possible look the scientific method the scientific community it works on advances that are predicated on current and prior advances incremental advances are the coin of the realm it's not it's not that they're conservative it's just that the process the communal process of accepting truth as that which can't be negated causes you to therefore be in every which way questioning everything so and I learned long ago the expression organized skepticism that's what science is predicated on as a result if you come forward with something that is not fully supported by and connected to the current reality people don't know what to do with it now what what many academic scientists do is to spend the next five ten years putting the the connections in place to make what's being proposed you know kind of a natural extension of what existed before but in industry we don't have that need and the reason we were modern was able to really be the pioneer in the space of establishing a therapeutic platform even before a vaccine platform is because for us the lack of connection between what we were able to do and what had been done before was marginally interesting but not a we weren't trying to publish it we know when you patent something you don't have to show that it's a natural extension of what people did you just have to describe something that is novel that is unobvious in fact the less connected the more unobvious and or the less connectable you know my answer to your question would be a lot of it has to do with the essence of academic scientific pursuit of knowledge which causes this this collectivism and it has its disadvantages one of them is if you don't have all the pieces together people will be skeptical how should we improve the biomedical funding cycle well boy that's you're in charge we're going to do what you say tell us what to do no no yeah um no that would be that would be a difficult day for me just because i'd rather do things that people don't think should be done look i think i hope that the the illustration that a vaccine developed in a short period of time with robust at least early results hopefully making an impact on on the population should give people a use case from which to think that this is not some artisanal activity that you need a phd in molecular biology to be able to understand but rather a set of new tools a equivalent of a computing infrastructure for other sectors that has been put together it may not look like a computer but the assemblage of processing techniques and knowledge gathering and storing techniques has you know somewhat digital somewhat analog has created a capability that's why we call these platforms has created a set of platforms from which we can expect not just slightly better cures and slightly better treatments but pretty dramatic departures not once or twice but over and over and over again and i think society if that begins to be understood then biomedical funding should be thought of as as an enabler of the underlying science needed to keep making this happen so i want to make a strong case for what others call basic research which i'd rather call enabling research because inevitably basic research is enabling to something and so in a weird way sometimes academic research frames things as having no purpose whatsoever so that they could keep the purity of it but actually it's they can't even assure that because eventually somebody will come along and use that to for good i think all of it is for good so enabling research i understand it can be bad uses of science by the way parenthetically i'm not naive but i'm we're talking about biomedical now i think that enabling research and then followed by applied research where you do the translational work i would see it's just not about more money it's about being able to to invest in the areas where we're able to have impact and then create the conditions for future impact in the other areas now some institutions seem to be much more successful than others so broad institute in mit has had a string of successes howard use medical institute are those successes just luck or is there something systematic we can learn from the best performers and if so what is that what should we be doing more of no that's an excellent question first let me just say that being systematic is an advantage in and of itself in my view i know that that's not doesn't make me popular with with people who want to believe that exceptional things are by their nature unpredictable and rare and unreproducible i happen not to believe that i think that many things with him exceptional are illusions because we haven't actually gotten around to creating a systematic way to produce the conditions to have them happen and that's you know that's my personal belief so i would say in and of itself that the hhmi that the broad or you know the the cancer the various cancer institutes that exist have done some amazing things the welcome trust is a function of their systematic thinking about the job at hand so that's one and then of course it's about kind of leadership it's about the the patience inherent in the money look i let me say maybe something start which we at flagship believe and embody but maybe start in the context i'm saying it in which is that we have to be willing to embrace unreasonable propositions and unreasonable people in order to make extraordinary findings because the notion that utterly reasonable people doing utterly reasonable things will produce massive breakthroughs it doesn't compute to me because yes they can there's also such a thing as a lottery so every week somebody will win a hundred million dollars and that but the notion that our that we should go searching for extraordinary advances amidst what is otherwise kind of pretty reasonable things each connected to each other by short distances i i think that we need to allow for leaps to coexist with the hard work of filling in the gaps and so i think that those places you talked about in hhmi enables very few but importantly professors to have capital to do whatever they want to do uh and that's kind of guess what that's a leaping ability you know permission to leap maybe in the military way and then it broke uh you know a lot of what what the money that that that elie brode gave and the rest of it that has been assembled has been deployed to doing things that that are scientifically kind of with merit but merit and i would say not as dogmatically asserted as one would need if it was going to go through our whole funding process so i think some of that so i'd say encourage leaps create a culture where leaps are not only permitted but they're encouraged and they're protected so that if it doesn't work out that people celebrate that at some level and then have a systematic way to think about it so that there's learning cycles that come with that now as you know moderna has already issued a no comment statement on the policy idea of first doses first for vaccines in general when should companies whether it's flagship or moderna speak out on policy because you all know the most yet at the same time you have a fiduciary responsibility to the shareholders of the company and how do you weigh off speaking out on policy issues versus your duties to the company that's a that's a very tough question and i think it's answered largely on a case by case basis which is inadequate but necessary particularly given that we're in uncharted territory there is such a heightened degree of of scrutiny on every single word that's that's uttered and amplification and potentially misdirection that i think that we have to be even more careful plus i think people in a pandemic are vulnerable to believing excesses and and we don't want to kind of play into that by being misconstrued so one the first thing is utmost care second is in the right context so we have the ability to to express our views on policy in places where those are are relevant with government colleagues with certain nonprofits that are focused on issues but we have to be as you said careful about that because of the the way in which the world is processing information on these things it's not easy it's it's not an easy situation for any of us now when it comes to the boston cambridge area as an innovation center what is both its greatest underappreciated strength and its least recognized drawback boy you have you've thought about the questions a lot more than i've thought about the answers uh because you're asking me can kudos to you asking me a lot of questions that uh that i don't typically answer i think that you know boston is is its own uh as its own culture it's beautifully filled with immigrants that constantly reconstitute that culture but at the same time it has roots it has it has a history that kind of gives it a i'd say a rootedness you can't live in boston for a long period of time and not feel like you're part of something that has been there and that is this kind of so that so the beauty is there are institutions that are real class and and i think that all of those conditions helped the biotech ecosystem take hold you know frankly there was no biotech or ecosystem when i started i remember in 1987 i started my first company and i was quite young i was 24 years old and at the time young people didn't start any companies and i was interviewed by ink magazine i remember it distinctly and they pointed out that the office i was in was was previously the office of a company that had failed and how did i feel about that and and my response was that i did not think about whose office i was occupying i thought about the office of then the most notable iconic but a non biotech but the startup success in boston which was lotus and lotus was just across the street from from where i was and i said i choose to look at that office as opposed to looking at who might have had a business card at my desk and and that that kind of forward-looking culture has developed at least in boston because boston i think is a place where you definitely can feel like anything's possible you know you have world-class institutions that educate people enable them to believe that and then i think what's happened over the last 30 years what's really not appreciated is that ecosystems aren't designed or constructed they emerge they are a highly kind of ecological concept and in nature you really got to realize that many many forces that that apply to things through iterative cycles it caused an emergent kind of form either way it's a life form or a community form and i think that's the best way to understand boston's ecosystem so when people kind of talk about reproducing the boston ecosystem or for that matter silicon valley more dispersed but but similar kind of things i think that's very very difficult because you'd have to reproduce the emergent trajectory that's my view there's people who publish books that say the opposite but so i'd say that's less understood maybe is in the category of just how a product of the sequence of events an emergent ecosystem is and i think what is what is appreciated is that this is a special moment for boston kainbridge and and really the biomedical enterprise the hospitals the large pharma companies that the human talent that's been attracted the key is going to be how not to necessarily preserve it in the way it is today but how to make sure you don't mess with the evolutionary experiment through policy here come the easy questions we we have a segment called overrated versus underrated i toss out a word or an idea you tell me if it's overrated or underrated plant biotech overrated or underrated let me make sure that you have to say more plant biotech as a as a future potential as a future potential say to protect against climate change on highly underrated tell us why because just like we understood very little about human health we understand even less about plant health and plant health is manifested in yield and resilience and drought and in the functionality of plants which we are other than feeding ourselves with or animals with done very little else with but we the technological capabilities are now absolutely upon us to be able to harness plants and their own ecosystems to do a lot more than just create food and and i think that that's just beginning so you know plant and we work in this area so i'm not saying this as a spectator i think in the 30 years i've been involved in biotech where there was an initial kind of excitement but ended up with with monsanto going down a a genetic modification route the understanding of plants as kind of living productive systems that can be harnessed to do things including in climate is just beginning and i think it's got a lot of promise aram kachaturian overrated or underrated hardly known amazing artist and i wish everybody i mean obviously he's known for one major piece of music the saber dance but i would say overlooked in much of the world but by the hero to me where should someone start the piano concerto the ballet music what what would you say yes yes leveronian overrated or underrated uh appropriately highly rated jason tatum overrated or underrated well you know you're of course testing the limits of my my belief versus my hope and it's really hard to keep them apart i would i would like it to be underrated certainly not overrated what is the highlight of Armenian food in your opinion boy oh boy just one look at me and you'll realize that i'm not very discriminant in that regard um highlight of Armenian food you know well i mean Armenian food is is largely built around barbecue meat with a lot of barbecue vegetables so probably this notion of what's called chorovaz which means barbecue which is the centerpiece of what a lot of the main meals are uh there are refined things that Armenians make and eat but uh i'd say that i hate saying it is either the meat and potatoes or the of the cuisine are these kind of combined meat and vegetable dishes that are quite good so say i'm on fountain avenue in los angeles or rome and glendale and i want to find better rather than worse Armenian food how should i think about that conceptually what should i do uh yeah well let me go to a place where there's mostly Armenians and relatively less tourists as a usual algorithm that works beyond just with Armenians but i would say you know look i grew up with Middle Eastern army flavored Armenian food so kind of a fusion between Lebanese food and Armenian food and because Armenians have been spread all around the world uh we have fused our cuisine with wherever we end up and not say probably there's some pretty pretty interesting Armenian dishes you can get in glendale they could probably not get many other places but i won't profess extreme knowledge there's a place called finicia for example there that that is quite good but these are hybrid between Lebanese and Armenian i just happen to like that why is the city of montreal fallen into underrated status it was once the financial capital of canada right now it feels like a backwater what happened god well you know first of all montreal is where where my family escaped to from the civil war in lebanon at a time when people didn't think it was going to be a long lasting war and thanks to my now departed father and his vision we were among the first to get out and so montreal for me has this incredibly special place because that's where i grew up your question is is a tricky question because one i'd say in some areas it's certainly fallen a bit behind but in other areas is thriving uh get canada had a a period of time where there was a lot of infighting around language around laws around kind of some of those concepts of self between a bilingual society and i think that had some some impact on montreal's uh vibrancy because there was a big exodus of companies there was an influx of other ones and i think a lot of that has has largely passed now and so i think you know canada in general is itself i'd say underrated uh because it's got a lot of potential and it's got very progressive values and and and uh maybe a little less kind of at the edge the way the us is able to and willing to be but that's a choice they make that's their culture and so you know that would be my answer what do you love most in classical music oh boy what piece you mean i i love what composer what what let me tell you i love most but that's not for cognitive reasons that my mother was a classical pianist trained at the power's conservatory and when we grew up she played a lot of Chopin and so there are many Chopin pieces that are kind of you know kind of embedded into my into my cells i would say but but i more broadly i didn't have the ability to continue playing the cello which i learned growing up based on the fact that we moved and changed countries and that was a pretty disruptive event in our lives but i'm happy to enjoy classical music and and and with together my wife but i don't have a particular kind of piece or a particular hero in that regard obviously the major names but also once in a while trying to find out i'm very happy that the bass and symphony orchestra which i support have been involved with has a a strong commitment to new artists and new classical music intermixed with the more the older ones what is your armenia related philanthropic project that right now you are most excited about yeah that's that's there's a bunch of them but i'll say that you know we have we we have a um we created a humanitarian project which which was both a prize and a and a movement called aurora humanitarian initiative that was actually not armenia related but founded upon armenia's armenians experience with the genocide because the notion was that at the at the cent the centennial of the armenian genocide which was in 2015 the commemoration that we needed to kind of look forward by looking back and expressing gratitude to the people who saved my grandparents for example back in 2019-15 but instead of thanking them because they'd long gone to to step into the shoes of the people who're doing that today and give them the financial means the recognition and the worldwide so aurora humanitarian initiative is a project that i'm quite proud of and involved with now what's happened is that unexpectedly armenia itself in the last few months has been thrust into a humanitarian disaster by virtue of a war that's been going on with with its neighbor uh for hope fortunately recently it they entered into a peace accord but the resultant damage done to thousands and thousands of families and tens of thousands of lives is immense so now what's happened is that this aurora initiative that was a gift from armenians to the world to thank people in Africa in in in Myanmar in different places doing humanitarian work has now focused some of its attention in providing help to the very same armenians that a hundred years later are afflicted with this again the irony is painful but i'm proud of our ability to contribute to a pretty dire situation now you think about company building in a pretty different way do you also think about philanthropy in a different way and what would you describe as the unity across your approach to companies and your approach to philanthropy well this is becoming a excruciating pattern uh the parallelism the parallel between the two has over the years uh struck me and it's been kind of almost instructive because i i used to keep kind of those two sides of my life quite nicely separated and what i found was that was that some of the things that we were doing in flagship with the way we thought about kind of the future backwards approach kind of what's the what's the destination you want to reach and how do you get there seems like a simple idea quite absent when you're trying to react to people's needs because people's needs are here and now they're not really forward looking you know education is meant to be something the government provides because its impact is kind of slowly felt but so is economic development so is many things so so i'd say that the the crossover has been on the on in terms of the relationship with the future so i for example in the philanthropy work that we've done in particular with respect to developing our media which has been going on for 20 years now the central i i've decided that our our customer is a five-year-old today uh i say five-year-old to make it concrete but basically somebody that can either vote nor can express what they wish the future looks like but for whom we want to try to create a more reasonable life and a more safe existence and sustainable existence so in terms of that that's not that different than a startup where you often can't describe your customer but it's somebody that will at some point need an inject into their body to make a vaccine that might save their lives but but nevertheless describing it future backwards and being anchored in the future as opposed to anchored only in the present or past that thinking does affect very much the philanthropy that i've been involved with when do you think human beings will start living to age 140 in okay enough shape tricky question i've i have um yeah i assuming that that would be a desirable outcome is is is a is a big assumption for me um i don't want to guess on that and i i tell you why i have a for for somebody who has a few bounds on what i'm willing to imagine i think that longevity as a goal versus longevity as a result uh are are you know separate the way in which you know different people think i think of longevity as a result i think that if we can deliver on on health security that is getting people most of their lives to be defended in terms of their health versus treated with their diseases chances are the result of that will be longer and longer lives but also longer healthier lives and presumptively happier lives the notion that we can come up with disease treatments that keep people alive but are largely just fighting the disease uh and with with all the damage that it's already done that to me is a less desirable future vision when do you think we will arrive at the point where dementia and Alzheimer's they may still be present but they will not be significant social problems in the wealthiest countries i'd like to see a a more credible direction there over the last five over the next five to ten years and so that it will have impact in the 10 to 20 year time frame i don't see if i just roll back the clock 20 years much of what we're doing today south therapies messenger RNA microbiome none of those existed or were dreamt of uh largely and so i think if i just use that yardstick to go forward that level of both increased knowledge about the the pathophysiology coupled with increased tools to address it with i may be being too conservative but let's see over the next five ten years proof points clear proof points that that's where the reach should emerge here's a very hard question again what is the most important ethics question you face in your biosciences work and how do you handle it or think about it you know we have being in this space uh there's a lot of ethical issues uh ranging from kind of what what you're willing to do in terms of genetic genomic modifications uh to the ethics of supply and availability of of vaccines uh to what do you do with people who are who have volunteered for trials and now you know that there's a way to treat them but that might cause different challenges there it's just it's it's not the case that you know ethical issues come up rarely they come up a lot and what i what i do is try to kind of get as many people of different backgrounds and mindsets to talk about it uh and and and you know kind of get external input but also internal we've got to we're lucky to have a pretty pretty diverse set of folks who have points of view about things and try to arrive at at least a a a thesis but be open minded to revisit it as data emerges i'm you know i'm i'm quite i've long practiced maybe it's out of my ignorance the notion that many things there may not be a definite answer for but you need an answer in order to persist to come up with a better answer and it may be the opposite answer and so you're not done answering it but you still need to proceed so there are things you know i'm not of course there are things in the ethical realm that are pretty crystal clear you know but but the more interesting things are not and they need to they need to be discussed and iterated what do you think is the most conceptual or most structural reason why lebanon has been so politically unstable uh i won't profess expertise in this area other than it's my birthplace and i i live 13 years of my life enjoying what seemed in hindsight as a disney ride it was a an idyllic place it was a fun place it had a lot of different cultures commingled seemingly harmoniously just you know mountains and and sea and you name it but it turns out that a lot of the seeming societal um kind of stability that i thought we lived with it in the in the decade that i lived there or so was kind of a was was a surface on on a volatile situation i think that what happened in the middle east um basically led to displacement of populations some of which came to lebanon of course there was a large pashtunian contingent there that kind of was looking for the world to to help it and and administer its its fate or or help it with its fate after the after the wars that took place and so it was a it was an unstable place that that you know clearly the way it was put together uh you know post world war one and the way the governance was decided upon there were very forward looking things done but actually they did not prove stable uh that plus you know used to be the financial capital of the region and and and you know once you have a civil war abstracted one of that then that's a fleeting advantage in that it moved to other places like dubai and other places now so you know what single thing contributes to it um it's easier for me to answer how lebanon has endured despite those things which is a an incomparable degree of optimism about things getting better i mean it's really genetic uh in in that in that country and i think to some extent probably it's what what makes them survive is what might also condemn them to go back there because they may not spend as much time to try to address the underlying conflicts and underlying incompatibilities to so many different fractions trying to coexist there as one would like in order to maybe trade off the short-term optimism for long-term durability but that's as an outsider i haven't lived there for some 45 years but i i view lebanon in the context of my the prism of our media which has in some ways similar problems in that you know when you've we have a rather optimistic population despite the setbacks and you got to ask yourself is the optimism sometimes hurting you or helping you sometimes it can hurt you if it doesn't if it makes you accept the next illusion or the next fiction versus actually dealing with tough problems you've described your own approach as a kind of paranoid optimism and you got that from lebanon in your lebanese background or your armenian background you probably didn't get it from canada how did you get that probably my armenian background and i would say i realized i i've i've viewed paranoid optimism as a mindset that is advantageous in in in entrepreneurship particularly when you go to the far edges of what is known as a as almost a survivalistic thing but i never ever associated with my kind of armenian roots or the history of of what armenians have endured until some five six years ago when my world's kind of collided a bit and and i had to i found myself talking about these kind of survivalistic mindsets in both of the world the world of innovation is very much one of of toggling between survival and thriving i wish there was a word tribal but i haven't quite managed to get that word in the dictionary but that's a good word but between surviving and thriving in this constant toggle between the two characterizes high risk daring startups and just like it does within a recovering population where they've been afflicted with massive trauma and they have to on the one hand survive but on the other hand not get trapped in the ghetto of just survival and try to escape it and try to thrive and i think those that's probably where the life experiences have have at least helped but i cannot draw a connection because it was not conscious at all three final questions all about you first what is your most unusual effective work habit unusual effective work habits you take notes on everything you wake up at four a m in the morning you have a glass of orange juice before every meeting those are highly those are highly precedent that i'd say maybe less about a work habit but rather a because much of my work is just talking to people effectively you know it's kind of the the instrument that i play is is really just dialogue and discourse and in that regard the one thing that i i believe in is that i've said this to you i've got a strongly evolutionary kind of mindset and and this notion of emergence so i think that if you're doing something that's never been done before you have to be very humble to recognizing that you don't know what the right thing to do is but also nobody else does and in that milieu you need to create a culture where people are willing to say things and be wrong so that others can say other things and over time whatever is right can emerge so i'd say probably the most unusual thing that i insist on is people's willingness to say things that are not backed up by all the facts that one would typically need and then to engage them in a dialogue that will eventually get us there it's tiring it's not a pleasant activity but i've developed a sense of that because that i think that that gets you to new truths as opposed to repetitions of current dogma what book has had the greatest impact on you as a person god um i should have a standard answer to that uh and i will disappoint you in saying i don't have one i've had i've had an opportunity to read a number of books growing up i read books less books now and they have often to do with kind of entertainment to me as opposed to kind of content uh so i'm going to disappoint myself in not giving you a singular answer but tell us an entertaining book just one that entertains you Jean Lacarré or what what would it be you know i read a couple years ago this book i think it was called Origins i want to say by Dan Brown if it wasn't by Dan Brown it was probably somebody like Dan Brown because it seemed like that the kind of series it was about kind of ai in the context of some mystery novel and that book for example entertain me i'm just giving a an example of it there there's yeah if i if i thought enough about it i could give you two three good answers but i'll just throw that out i think it's called Origins i think it's by Dan Brown last question how do we attract more people like you to come to America be America what does that mean uh what i mean is uh recognize that that the country is itself one giant experiment it's a melting pot it has been a melting pot it should continue to be a melting pot a melting pot means that people come here to effectively make the country like them and themselves make like the country and that that dissolution is not a source of negative i know there's lots of people who who kind of want to create ethnic differences and all the differences among us but there's an element of this where where i think people have come to this country fully intending to to adapt and to contribute but also to add of themselves to what is considered America today and i i think that that system that cooperative system between the precedented and the new uh is what accounts for you know unimaginable creativity resilience resourcefulness that this country has and i i would protect that far greater than any monument or any other national treasure uh i think i think that's so that's that's that's personally you know it may seem romantic but that's what i think is attractive about this country uh because this country has that that as a core advantage and and i think that's a tough thing to pull off let me tell you a lot of other countries that kind of come and go and civilizations who don't have that who become a bit more homogeneous more exclusionary kind of lose their i'll say it evolutionary advantage their competitive advantage to adapt and to respond and so i think we clearly have a bunch of things to fix as it relates to the way the governance of the country is is being executed uh there's there's a level of over maturation of that and over stagnation of that that seems that seems very very troubling uh and and i don't know how that gets changed is beyond my my experience base but i would say whatever happens should and i'm by the way i have not said should protect immigrants or immigration but should protect this dynamism that that comes from that i also would say that as a country there's so many people who have the experience of coming here that that experience can also be transmitted to people who are born here for whom the same mindset of being willing to imagine a better look every single person who comes to this country imagines a better future for themselves that's my belief maybe not every single person 99 so imagine if all of us were also born imagining a better future for ourselves well we should be but we got to work to get that an immigrant who comes here understand that they got to work to get that they have to adapt the problem is if you're born here you may not actually think that you're going to work to get that you might think you're born into it and if we're all you know i this will be kind of a funny thing to say and i apologize to anybody that i offend if we were all americans by choice we'd have a better america because americans by choice of which i'm one actually have a stronger commitment to whatever it takes to make america be the place i chose to be versus you know not thinking about that as a as a as a core responsibility so i i i think that that is something to be said about that is to really make a new pact a compact to say what's the america that i really want to be contributing to and if that's more equal less discriminating you know different rules and and laws etc but we should we should be open to talk about those things new bar if i thank you very much thank you