Robert Langer: Edison of Medicine | Lex Fridman Podcast #105
the following is a conversation was Bob Langer professor at MIT and one of the most cited researchers in history specializing in biotechnology fields of drug delivery systems and tissue engineering he has bridged theory and practice by being a key member and driving force in launching many successful biotech companies out of MIT this conversation was recorded before the outbreak of the corona virus pandemic his research and companies are at the forefront of developing treatments for covert 19 including a promising vaccine candidate quick summary of the ads to sponsors cash up a master class please consider supporting the podcast by downloading cash app and using code Lex podcast and signing up a masterclass comm slash Lex click on the links buy this stuff it really is the best way to support this podcast and in general the journey I'm on to my research and startup this is the artificial intelligence podcast if you enjoy it subscribe bye YouTube review it with five stars in a podcast supported on patreon or connect with me on Twitter Lex Friedman as usual I'll do a few minutes of ads now and never any ads in the middle that can break the flow of the conversation this show is presented by cash app the number one finance app in the App Store when you get it use collects podcast cash app lets you send money to friends buy bitcoin and invest in the stock market with as little as one dollar since cash app allows you to send and receive money digitally let me mention a surprising fact related to physical money of all the currency in the world roughly eight percent of it is actual physical money the other 92 percent of money only exists digitally so again if you get cash app from the App Store or Google Play and use the collects podcast you get ten dollars and cash wrap will also donate ten dollars the first an organization that is helping to advance robotics and STEM education for young people around the world this show sponsored by masterclass sign up a master class complex to get a discount and to support this podcast when I first heard about master class I thought it was too good to be true for one hundred and eighty dollars a year you get an all-access pass to watch courses from to list some of my favorites Chris Hadfield on space exploration Neil deGrasse Tyson a scientific thinking and communication will write to crater some city and Sims on game design Carlos Santana on guitar Europa is probably one of the most beautiful guitar instrumentals ever garry kasparov on chests daniel negreanu on poker and many more Chris Hadfield explaining how Rockets work and the experience of being launched into space alone is worth the money you can watch it basically any device once again sign up a master class calm slash flex to get a discount and to support this podcast and now here's my conversation with Bob Langer you have a bit of a love for magic do you see a connection between magic and science I do I think magic can surprise you and you know and I think science can surprise you and there's something magical about about science I mean making discoveries and things like that you know so on then on the magic side is there some kind of engineering scientific process to the tricks themselves do you see because there's a duality to it one is your the your you're sort of the person inside there knows how the whole thing works how the universe of the magic trick works and then from the outside observer which is kind of the role of the scientists you the people that observe the magic trick don't know at least initially anything that's going on do you see that kind of duality well I think the duality that I see is fascination you know I think of it you know when I watch Magic myself I'm always fascinated by it sometimes it's a puzzle to think how it's done but just the sheer fact that's something that you never thought could happen does happen and I think about that in science too you know sometimes you it's something that you might dream about and helping to discover maybe you do or in some way or form what is the most amazing magic trick you've ever seen well there's one I like which is called the invisible pack and the way it works is you have this pack and you hold it up but first you say to somebody is this is invisible and this deck and you say well shuffle it and I shuffle it but you know there's sort of make-believe and then you say okay I'd like you to pick a card any card and show it to me and you show it to me and and I look at it and let's say it's the three of hearts and said we'll put it back in the deck but what I'd like you to do is turn it upside down from every other cards in the deck so they they do that imaginary and I said you want to shuffle it again they shuffle it and I said well so there's still one card upside down from every other card in the deck I said what is that and they said all three hearts so it just so happens in my back pocket I have this deck it's you know it's a real deck I show - you know it's just open it up and there's just one card upside down and it's the three of hearts and and you can do this trick I can i-55 don't I would have probably brought it all right well beautiful let's get into the into the science as of today you have over two hundred ninety five thousand citation an h-index of 269 you're one of the most sighted people in history and the most cited engineer in history and yet nothing great I think is ever achieved without failure so the interesting part what rejected papers ideas efforts in your life or most painful or had the biggest impact on your life well it's interesting I mean I've had plenty of rejection to you know I but I suppose one way I think about this is that when I first started and this certainly had an impact both ways you know I first started we made two big discoveries and they were kind of interrelated I mean one was I was trying to isolate with my post-doctorate advisor Judah Folkman substances that could stop blood vessels from growing and nobody done that before and so that was part a let's say a Part B is we had to develop a way to study that and what was critical to study that was to have a way to slowly release those substances for you know more than a day I you know maybe months and that had never been done before either so we published the first one we sent to nature the journal and they rejected it and then we sent it revise tenets of science and they accepted it and the other the opposite happened we sent it to science and they rejected it and then we sent it to nature and they accepted it but I have to tell you when we got the rejections it was really upsetting I thought you know I did some really good work and dr. Folkman thought we've done some really good work and and but it was very depressing to you know get rejected like that if you can linger on just the feeling or the thought process when you get the rejection especially early on in your career what I mean you don't know now people know you as uh as as a brilliant scientist but at the time I'm sure you're full of self-doubt and did you believe that maybe this idea is actually quite terrible that it could been done much better or is the underlying confidence what was the feelings well you feel to feel depressed that I felt the same way when I got grants rejected which I did a lot in the beginning I guess part of me you know you have multiple emotions one is being sad and being upset and also being maybe a little bit angry because the you to feel the reviewers didn't get it but then as I thought about it more I thought well maybe I just didn't explain it well enough and you know that you go through stages and so you say well okay I'll explain it better next time and certainly you get reviews and what you get the reviews you see what they either didn't like or didn't understand and then you try to incorporate that into your next versions mmm you've given advice to students to do something big do something that really can change the world rather than something incremental how did you yourself seek out such ideas is there a process is there a sort of a rigorous process or is it more spontaneous it's more spontaneous I mean part of its exposure to things part of its seeing other people like I mentioned dr. Folkman he was my post doctoral adviser he was very good at that you could sort of see that he had big ideas and I certainly met a lot of people who didn't and and I think you could spot an idea that might have potential when you see it you know because it could have a very broad implications where a lot of people might just keep doing derivative stuff and so but it's not something that I've ever done systematically I don't think so in the space of ideas how many are just when you see them it's just magic it's something that you see that could be impactful if if if you dig deeper yeah it's it's sort of hard to say because there's there's multiple levels of ideas one type of thing is like a new you know creation like that you could engineer tissues for the first time or make dishes from scratch from the first time but another thing is really just deeply understanding something and that's important too so and and that may lead to other things so sometimes you could think of a new technology or I thought of a new technology but other times things came from just the process of trying to discover things so it's never and and and you don't necessarily know like people talk about aha moments but I don't know if I've I mean I certainly feel like I've had some ideas that I really like but it's taken me a long time to go from the thought process of starting it to all of a sudden knowing that it might work so if you if you take drug delivery for example is the notion is the initial notion kind of a very general one that we should be able to do something like this yeah and then you start to ask the questions of well how would you do it and then and then digging and digging and digging I think that's right I think it depends I mean there are many different examples the example I gave about delivering large molecules which we used to study these blood vessel inhibitors I mean there we had it invent something that would do that but other times it's it's it's different sometimes it's really understanding what goes on in terms of understanding the mechanisms and so it's it's it's not a single thing and there are many different parts to it you know over the years we've invented different discover different principles for aerosols for delivering you know genetic therapy agents you know all kinds of things so let's explore some of the key ideas you've touched on in your life some let's let's start with the basics okay so first let me ask how complicated is the biology and chemistry of the human body from the perspective of trying to affect some parts of it in a positive way it's but so that you know for me especially coming from the field of computer science and computer engineering and robotics it's that the human body is exceptionally complicated and how the heck you can figure out anything is amazing well I agree with you I think it's super complicated I mean we're still just scratching the surface in many ways but I feel like we have made progress in different ways and some of its by really understanding things like we were just talking about other times you know you might or somebody might we or others might invent technologies that might be helpful on exploring that and I think over many years we've understood things better and better but we still have such a long ways to go are there I mean if you just look are there other things that are there knobs that are reliably controllable about the human body if you could service is there is it so if you start to think about controlling various aspects of when we talk about drug delivery a little bit but controlling various aspects chemically of the human body is there a solid understanding across the populations of humans that are solid reliable knobs that can be controlled I think that's hard to do about on the other hand whenever we make a new drug or medical device to a certain extent we're doing that you know in a small way what you just said but I don't know that they're that they're great knobs I mean and we're learning about those knobs all the time but if there's a biological pathway or something that you can affect or understand I mean then that might be such a knob so what is pharmaceutical drug how do you do how do you discover a specific one how do you test it how do you understand it how do you ship it yeah well I'll give an example which goes back to what I said before so when I was doing my postdoctoral work with Judah Folkman we wanted to come up with drugs that would stop blood vessels from growing or alternatively make them grow and actually people didn't even believe that that those things could happen but could we pause on that for a sec sure what is the blood vessel what does it mean for a blood vessel to grow and shrink and why is that important sure so a blood vessel is could be an artery or vein or a capillary and it it you know provides oxygen it provides nutrients gets rid of waste so you know two different parts of your body if you soso the blood vessels end up being very very important and you know if you have cancer blood vessels grow into the tumor and that's part of what enables the tumor to get bigger and that's also part of what enables the tumor to metastasize event which means spread throughout the body and ultimately kill somebody so that was part of what we were trying to do we shot what we wanted to see if we could find substances that could stop that from happening so first I mean there are many steps first we had to develop a bio essay to study blood vessel growth again there wasn't one that's where we needed polymer systems because the blood vessels grew slowly took months that so after we had the polymer system and we had the bioassay then I had isolated many different molecules initially from cartilage and almost all of them didn't work but we were fortunate we found one it wasn't purified but we found one that did work and that paper that was this paper I mentioned in science in 1976 those were really the isolation of some of the very first angiogenesis of blood vessel inhibitors so there's a lot of words there yeah that's the the first of all polymer molecules big big molecules so the water polymers what's bio sa the the what is the process is trying to isolate this whole thing simplified to where you can control and experiment with it polymers are like plastics or like plastics or rubber what were some of the other questions sorry so a polymer some plastics and rubber and that means something that has structure and that could be useful for what well in this case it would be something that could be useful for delivering a molecule for a long time so it could slowly diffuse out of that at a controlled rate to where you wanted it to go so then you would find the ideas that there would be particular blood vessels that you can target say they're connected some Auto tumour you could target and over a long period of time to be able to place the polymer there and it be delivering a certain kind of chemical that's correct I think what you said it's good so so that it would deliver the the molecule or the chemical that would stop the blood vessels from going over a long enough time so that it really could happen so that was sort of the what we call the bio sa is the way that we would study that so size of what is a by us which part is the bio sa all of it in other words the bio SAS is the way you study blood vessel growth the blood vessel growth and you can control this somehow with is there an understanding what kind of chemicals can control the growth of a blood sure well now there is but then when I started there wasn't and that that gets to your original question so you go through various steps we did the first steps we showed that a such molecules existed and then we developed techniques for studying them and we said even isolated fractions you know groups of substances that would would do it but what would happen over the next we did that in 1976 we published that what would happen over the next twenty eight years as other people would follow in our footsteps I mean we tried to do some stuff too but ultimately to make a new drug takes billions of dollars so what happened was there were different growth factors that people would isolate sometimes using the techniques that we developed and then they would figure out using some of those techniques ways to stop those growth factors and ways to stop the blood vessels from growing I thought like you say it took 28 years it took billions of dollars and work by many companies like Genentech but in 2004 28 years after we started the first one of those Avastin got approved by the fda and that that be that's become you know one of the top biotech selling drugs in history and it's been approved for all kinds of cancers and actually for many eye diseases to where you have abnormal blood vessel growth macula so in general one of the key ways you can alleviate so what's the hope in terms of tumors associated with cancerous tumors they what can you help by being able to control the growth of vessels so if you cut off the blood supply you cut off the it's kind of like a war almost right you if you have if the nutrition is going to the tumor and you and you and you can cut it off I mean you starve the tumor and it becomes very small it may disappear or it's going to be much more amenable to other therapies because it is tiny you know like you know chemotherapy or immunotherapy is gonna be have a much easier time against a small tumor than a big one is that an obvious idea I mean it seems like a very clever strategy in this war against yeah cancer well you know in retrospect it's an obvious idea but when dr. Folkman and my boss first proposed it it wasn't a lot of people didn't thought it was pretty crazy and so they in what sense if you could sort of linger on it when you're thinking about this ideas at the time were you feeling you're out in the dark so how much mystery is there about the whole thing how much just blind experimentation if you can put yourself in that mindset from years ago yeah well there was I mean for me actually it wasn't just the idea was that I didn't know a lot of biology or biochemistry so I've certainly felt a host in the dark but I I kept trying and I kept trying to learn and I kept plugging but but I mean a lot of it was being in the dark so the human body is complicated right we'll establish this quantum mechanics and physics is a theory that works incredibly well but we don't really necessarily understand the underlying nature of it so our drugs the same and that you can you're ultimately trying to show that the thing works to do something that you try to do but you don't necessarily understand the fundamental mechanisms by which it's doing it it really varies I think sometimes people do know them because they've figured out pathways and wish to interfere them with them other times is shooting in the dark is it really has varied okay and sometimes people make sure--and Jupitus discoveries and they don't even realize what they did so what is the discovery process for a drug ze said a bunch of people of trying to work with this is it is it a kind of mix of serendipitous discovery and art or is there a systematic science to trying different chemical reactions and how they how they affect whatever you trying to do like shrink blood vessels yeah I don't think there's a single way you know single way to go about something in terms of characterizing the entire drug discovery process if I look at the blood vessel one yeah they're the first step was to do to have that those kinds of theories that dr. Folkman had the second step was to have the techniques where you could study blood vessel growth for the first time and at least quantitate or semi-quantitative a third step was to find substances that would stop blood vessels from growing for step was to maybe purify those substances there are many other steps too I mean before you have an effective drug you have to show that it's safe you have to show those effective and you start with animals you ultimately go to patients and there are multiple kinds of clinical trials you have to do if you step back is it amazing to you that we descendants of great apes are able to create things there you know are the create drugs chemicals that are able to improve some aspects of our bodies Hey or is it quite natural that we were able to discover these kinds of things well at a high level it is amazing I mean evolution is amazing yeah you know the way I look at your question the fact that we evolved have evolved the way we've done I mean it's pretty remarkable so let's talk about drug delivery what are the difficult problems in drug delivery what is drug delivery you know from starting from your early seminal work in the field that today well drug delivery is getting a drug to to be good to go where you want it at the level you want it in a safe way some of the big challenges I mean there are a lot I mean I'd say one is could you target the right cell like we talked about cancers or some way to deliver a drug just to the cancer cell and no other cell another challenge is to get drugs across different barriers like could you ever give insulin orally could you give a train you know or give it passively transdermally can you get drugs across the blood-brain barrier I mean there are lots of big challenges can you make smart drug delivery systems that might respond to physiologic signals in the body oh it's just think so smart smart they have some kind of sense a chemical sensor or is this something more than a chemical sense that it's able to respond to something in the body could be either one I mean you know I I mean one example might be if you that were diabetic if you had more it got more glucose could you get more insulin but I don't but that but that's just an example is there some way to control the actual mechanism of delivery in a response to what the body's doing yes there is I mean one of the things that we've done is encapsulate what are called beta cells those are insulin producing cells in a way that they're safe and protected and then what will happen is glucose will go in and you know to sell so we'll make insulin and so that that's an example so from an AI robotics perspective how close are these drug delivery systems to something like a robot or they're totally wrong to think about them as intelligent agents and how much room is there to add that kind of intelligence into these delivery systems perhaps in the future yeah I think it depends on the particular delivery system you know of course one of the things people are concerned about is cost and if you add a lot of bells and whistles to something it'll cost more but I mean we for example have made what I'll call intelligent microchips that can don't you know where you can send a signal and you know release drug in response to that say no and I think systems like that microchip someday have the potential to do it you and I were just talking about that there could be a signal like glucose and it could have some instruction to say when there's more glucose deliver more insulin so do you think it's possible that there that could be robotic type systems roaming our body sort of long-term and be able to deliver certain kinds of drugs in the future you see you see that kind of future someday I don't think we're very close to it yet but someday you know that that's nanotechnology and that would mean even miniaturizing some of the things that I just discussed and we're certainly not at that point yet but someday I expect we will be so some of it is just the shrinking of the technology that's a part of it that's one of the things in general what role do you see AI sort of there there's a lot of work now with using data to make intelligent and create systems that make intelligent decisions do you see any of that data-driven kind of computing systems having a role in any part of this into the delivery and drugs the the design of drugs and any part of the chain I do I think that AI can be useful and a number of parts of the chain I mean one I think if you get a large amount of information you know say you have some chemical data because you've done high throughput screens and let's out I'll just make this up but let's say I have I'm trying to come up with a drug to treat disease X and whatever that disease is and I have a test for that and hopefully a fast test and let's say I test ten thousand chemical substances you know and a couple work most of them don't work so I maybe work a little but if I had a few with the right kind of artificial intelligence maybe you could look at the chemical structures and look at what works and see if there's certain commonalities look at what doesn't work and see what commonalities there are and then maybe use that somehow to project the next generation of things that you would test as a tangent what are your thoughts on our society's relationship with pharmaceutical drugs do we and perhaps I apologize if this is a philosophical broader question but do we over rely on them do we properly prescribed them and what ways the system working well what way can improve well I think you know pharmaceutical drugs are really important I mean the life expectancy and life quality of people over many many years has increased tremendously and I think that's a really good thing I think one thing that would also be good as if we could extend that more and more to people in the developing world which is something that our lab has been doing with the Gates Foundation or trying to do I saw I think ways in which it could improve I mean our if there was some way to reduce costs you know that that's certainly an issue people are concerned about if there was some way to help people and in poor countries that would also be a good thing and then of course we still need to make better drugs for so many diseases I mean cancer diabetes I mean we you know it's hard to see some rare diseases there are many many situations where it would be great if we could do better and help more people can we talk about another exciting another exciting space which is tissue engineering what is tissue engineering or regenerative medicine you know so that tissue engineering regenerative medicine have to do with building an organ or tissue from scratch so you know someday maybe we can build the liver you know or make new cartilage and also would enable you to you know someday create organs on a chip which people we and others are trying to do which might lead to better drug testing and maybe less testing on animals for people organs and I chip it sounds fascinating so what what are the various ways to generate tissue and how do so is it you know that one is of course from stem cells is there are other methods what are the different possible flavors here yeah well I think I mean there's multiple components one is having generally some type of scaffold that's what Jay Vacanti and I started many many years ago and then on that scaffold you might put different cell types which could be a cartilage cell a bone cell could be a stem cell though it might differentiate into different things could be more than one cell and the scaffold sorry to interrupt is kind of like a canvas that it's a structure that you can on which the the Susskind girl I think that's a good explanation when you just enough to use that the caskets that's good yeah so I think that that's fair you know when the chip could be such a canvas some could be fibers that are made of plastics and that you'd put in the body someday and we need a chip do you mean electronic chip like necessarily it could be though but it doesn't have to be it could just be a structure that's not not in vivo so to speak that's you know that's outside the body so is there a nervousness it's not a bad word says there possibility to weave into the scanner as a computational component so if we talk about electron ships some some ability to sense control some aspect of this growth process for the tissue I would say the answer to that is yes I think right now people are working mostly on validating these con chips for saying well it does work as effectively or hopefully as just putting something in the body but I think someday will you suggest it you certainly would be possible so what kind of tissues can we engineer today what would yeah yeah well well so skin has already been made and approved by the FDA their advanced clinical trials like what are called phase three trials that are at complete or near completion for making new blood vessels one of my former students Lorin Nicholson led a lot of that he thought that's amazing this human skin can be grown that's already approved through the entire the FDA process so that means what so the one that means you can grow that tissue and do various kinds of experiments in terms of in terms of drugs and so on but what is that does that mean that some kind of healing and treatment of different conditions for on human beings yes I mean they've been approved now for how many different groups have made them different companies and different professors but they've been approved for burn victims and for patients with diabetic skin ulcers that's amazing okay so skin what else well at different stages people are like skin blood vessels there's clinical trials going now for helping patients here better for patients that might be paralyzed for patients that have different hai problems I'm you know at different groups have worked on just about everything new liver and who kidneys I mean there have been all kinds of work done in this area some of its early but but there's certainly a lot of activity what about neural tissue yeah nurten the nervous system and even the brain while there have been people out of working on that too we've done a little bit with that but there are people who've done a lot on neural stem cells and I know Evan Schneider who's been one of our collaborators on some of our spinal cord works done work like that and ever been other people as well as their challenges for the when it is part of the human bodies there's challenges to getting the the body to accept this new tissue that's being generated how do you solve that kind of challenge there can be problems with it accepting it I think maybe in particular you might mean rejection by the body so there are multiple ways that people are trying to deal with that one way is which was what we've done and with Dan Anderson one of my former postdocs and I mentioned this a little bit before for a painted pancreas is encapsulating the cell so immune immune cells or antibodies can't get in and attack them so that's a way to protect them other strategies could be making the cells not immuno genic which might be done by different either techniques which might mask them or using some gene editing approaches so they're different ways that people are trying to do that and of course if you use the patient's own cells or cells from a close relative doubt might be another way and it increases the likelihood that they'll get accepted if you use the patient's own cells yes and then finally there's some you know suppressive drugs which you know will suppress the immune response that's right now what's done say for a liver transplant the fact that this whole thing works just fascinating at least from my outside perspective well we one day be able to regenerate any organ or part of the the human body in your view and it's exciting to think about future possibilities of tissue engineering is do you see some tissues more difficult than others what are the possibilities here yeah Wow of course I'm an optimist and I also feel a timeframe if we're talking about some day some day could be hundreds of years but I think that yes some day I think we will be able to regenerate many things and our different strategies that one might use the one might use some cells themselves one might use you know some molecules that might help regenerate the cells and so I think there are different possibilities what do you think that means for longevity if we look maybe not someday but 10 20 years out are the possibilities that tissue engineering the possibilities of the research that you're doing does it have a significant impact on the longevity human life I don't know that we'll see a radical increase in longevity but I think that in certain areas we'll see people live better lives and maybe so somewhat longer lives with the most beautiful scientific idea in biology nearing that you've come across in your years of research I apologize for the romantic no that's an interesting question I certainly think what is happening right now with CRISPR is a beautiful idea that certainly wasn't wasn't my idea I mean but you know I think it's very interesting here what what people have capitalized on is that there's a mechanism by which bacteria are able to destroy viruses and that understanding that let leads the machinery to to put you know to sort of cut and paste genes and and you know fix the cell so that kind of you see a promise for that kind of ability to copy and paste I mean everything like we said the human body is complicated is that Mele difficult to do I think it is exceptionally difficult to do but that doesn't mean they won't be done there's a lot of companies and people trying to do it and I think in some areas it will be done some of the ways that make you might lower the bar are not you know are just taking look like not necessarily doing it directly but you know you could take a cell that might be useful but you want to give it some cancer-killing capabilities something collect what's called the cart C cell and that might be a different way of somehow making a cart C cell and maybe making it better so there might be sort of easier things and rather than just fixing the whole body so the way a lot of things have moved to in medicine over time is stepwise so I can see things that might be easier to do than say fix a brain that would be very hard to do but maybe someday that'll happen too so in terms of stepwise that's the interesting notion do you see that if you look at medicine or bioengineering do you see that there is these big leaps that happen every decade or so or some distant period or is it a lot of incremental work not I don't mean to reduce its impact by saying it's incremental but yeah is there sort of phase shifts in in the science big big leaps I think there's both you know every so often a new technique or new technology comes out I mean genetic engineering was an example I mentioned CRISPR you know I think every so often things happen that you know make a big difference but still there's to try to really make progress make a new drug make a new device there's a lot of things I don't know if I'd call them incremental but there's a lot a lot of work that needs to be done absolutely so you have over numbers could be off but it's a big amount you have over 1100 current or pending patents that have been licensed sub license to over 300 companies what's your view would in your view are the strengths and what are the drawbacks of the patenting process well I think for the most part their strengths I think that if you didn't have patents especially in medicine you'd never get the funding that it takes to make a new drug or a new device I mean which according to Tufts to make a new drug costs over two billion dollars right now and nobody would even come close to giving you that money any of that money if if it weren't for the patent system because and then anybody else could do it that that that then leads to the negative though you know sometimes somebody does up a very successful drug and you certainly want to try to make it available to everybody and and so the patent system allows it allowed it happen in the first place but maybe it'll impede it after a little bit or certainly to some people or some companies you know once it's once it is out there what's the on the point of the cost what would you say is the most expensive part of the two billion dollars of making the drug given clinical trials that is by far the most in terms of money or pain or both well money but a pain goes hard to know I mean but but usually doing proving things that are that are proving that something new is safe and effective in people this is almost always the biggest expense could you linger on that for just a little longer and describe what it takes to prove for people that don't know in general what it takes to prove that something is effective on humans well you'd have to take at this particular disease but what the process is you start out with so usually you start out with cells then you'd go to animal models usually you have to do a couple of animal models and of course the animal models aren't perfect for humans and then you have to do three sets of clinical trials at a minimum a phase one trial to show that it's safe and small number of patients face to trial to show that it's effective in a small number of patients and a phase three trial to show that a safe and effective in a large number of pay and you know that could end up being hundreds or thousands of patients and they have to be really carefully controlled studies and you know you'd have to manufacture the drug you'd have to you know really watch those patients you have to be very concerned if you know that that it is gonna be safe and and and and you look at see does it doesn't treat the disease better than what the whatever the gold standard was before that if there was assuming there was one that's a really interesting line show that it's safe first and then that it's effective first do no harm first do no harm that's right so how again if you can linger it a little bit how does the patenting process work yeah well you you do a certain amount of research though that's not necessarily has to be the case but you for us usually it is usually we do a certain amount of research and make some findings and you know we had a hypothesis let's say we prove it or we make some discovery we need to invent some technique and then we write something up what's called a disclosure we give it to MIT technology transfer office they then give it to some patent attorneys and they use that and plus talking to us and you know work on writing a patent and then you go back and forth with the USPTO that's the United States Patent and Trademark Office and you know they may not allow it the first second or third time but they will tell you why they don't and you may adjust it and maybe you'll eventually get it and maybe you won't so you've been part of launching 40 companies together worth again numbers could be outdated but an estimated twenty three billion dollars you've described your thoughts on a formula for startup success so perhaps you can describe that formula in general describe what does it take to build a successful startup well I I break that down into a couple categories and I'm I'm a scientist and certainly from the science standpoint I'll go over that but I actually think that really the most important thing is probably the business people then that work with and you know they when I look back at the companies that have done well it's been because we've had great business people and when they haven't done as well we have it as good business people but from a science standpoint I think about that we've made some kind of discovery that is almost what I'd call a platform that you could use it for different things and certainly the drug delivery system example that I gave earlier z' is a good example of that you could use it for drug ABCDE and so forth and that I'd like to think that we've taken it far enough so that we've written at least one really good paper and a top journal hopefully a number that we've reduced it to practice in animal models that we've filed patents maybe I had issued patents that of what I'll call very good and broad claims that's sort of the key in a patent and then in our case a lot of times when we've done it a lot of times it's somebody in the lab like a postdoc or graduate student spent a big part of their life doing it and that they want to work at that company because they have this passion that they want to see something they did make a difference in people's lives maybe you could mention the business component it's funny to hear great side to say that there's value to business folks oh yeah well that always said so what what value what business instinct is valuable to make a startup successful a company successful I think the business aspects are you have to be a good judge of people so that you hire the right people you have to be strategic so you figure out if you do of that platform that could be used for all these different things what one are you and knowing that medical research is so expensive what thing are you gonna do first second third fourth and fifth I think you need to have a good Lex what I'll call FDA regulatory clinical trial trial strategy I think you have to be able to raise money incredibly so there are a lot of things you have to be a good good with people good manager people so the the money in the people part I get but this the stuff before in deciding the ABCD if you have a platform which trucks the first and taking testing you see nevertheless scientist is not being too always too good at that process well I think there a part of the process but I'd say there's probably I'm gonna just make this up but maybe six or seven criteria that you want to use and it's not just science I mean the kinds of things that I would think about is is the market big or small is the art there are there good animal models for it so that you could test it and it wouldn't take you know fifty years are the clinical trials that could be set up ones that you know have clear end points where you can make a judgement and and another issue would be competition are there other ways that some companies out there or doing it another issue would be reimbursement you know can I get reimbursed so a lot of things that you have manufacturing issues you'd want to consider is it not so I think there are really a lot of things that go into whether you do what you do for a second third or fourth so you lead one of the largest academic labs in the world with over ten million dollars in annual grants and over 100 researchers probably over a thousand since the labs beginning researchers can be individualistic and eccentric I don't put it nicely there you go eccentric so what insights into research leadership can you give having to run such a successful lab was so much diverse talent well I don't know that I'm any expert I think that what you do to me I mean I just want that missus gonna sound very simplistic but I just want people in the lab to be happy to be doing things that I hope will make the world a better place to be working on science that can make the world a better place and I guess my feeling is if we're able to do that you know Peter it kind of runs itself so how do you make a researcher happy in general what I think when people feel I mean this is going to sound like again simplistic or maybe like motherhood and apple pie but I think if people feel they're working on something really important that can affect many other people's lives and they're making some progress they'll feel good about it they'll feel good about themselves and they'll be happy but through brainstorming and so on what's your role and how difficult it is as a group in this in this collaboration to arrive at these big questions that might have impact well the big questions come from many different ways sometimes it's trying to things that I might think of or somebody in the lab might think of which could be a new technique or to understand something better but gee we've had people like Bill Gates and the Gates Foundation come to us and Juvenile Diabetes Foundation come to us and say gee could you help us on these things and I mean that's good too it doesn't happen just one way and I mean you've kind of mentioned it happiness but is there something more how do you inspire a researcher to do the best work of their life so you mentioned passion and passion is a kind of fire do you see yourself having a role to keep that fire going to to build it up to inspire the researchers through the you know pretty difficult process of going from idea to too big question to big answer I think so I think I try to do that by talking to people going over their ideas and their progress I try to do it as an individual you know certainly when I talk about my own career I had my setbacks s you know different times and people know that that know me and you know you just try to keep pushing and and so forth but but yeah I think I try to do that as the one who leads the lab so you have this exceptionally successful lab and and one of the great institutions in the world MIT what and yet sort of at least in my neck of the woods in computer science and artificial intelligence a lot of the research is kind of a lot of the great researchers not everyone but some are kind of going to industry a lot of them researchers moving to industry deep what do you think about the future of science in general is there drawbacks is a strength to the academic environment that you hope will persist how does it need to change what needs to stay the same what are your just thoughts in this whole landscape of science in its future well first I think going to industry is good but I think being an academia is good you know I have lots of students who have done both and they've had great careers doing both I I think from an academic standpoint I mean the biggest concern probably that people feel today you know at a place like MIT or other research heavy institutions is going to be funding and particularly funding that's not super directed you know so that you can do basic research I think that's probably the number one thing but you know it would be great if we as a society had come up with better ways to teach you know so that people all over could learn better you know so I think there were a number of things that would be good to be able to do better so again you're very successful in terms of funding but do you still feel the pressure of that of having to seek funding does it affect the science or is it or can you simply focus on doing the best work of your life and the funding comes along with that I'd say the last 10 or 15 years we've done pretty well funding but I always worry about it you know it's like you're still operating on more soft money than hard and and so I always worry about it but we've been fortunate that places have come to us like the Gates Foundation and others jovan Diabetes Foundation some companies and they're willing to give us funding and we've gotten government money as well we have a number of NIH grants and I've always had that and that's important to me too so so I worry about it but you know I just view that as a part of the process now if you put yourself in the shoes of a philanthropist it like say I gave you a hundred billion dollars right now but you couldn't spend on your own research mm-hmm so how how hard is it to decide which labs to invest in which ideas which problems which solutions you know cuz funding is so much such an important part of progression of science in today's society if you put yourself in the position of philanthropist how hard is that problem how would you go about solving it sure well I think what I do for the first thing is different philanthropists have different visions and I think the first thing is to form a concrete vision of what you want some people I mean I'll give just give you two examples of people that I know David Koch was very interested in cancer research and part of that was that he had cancer and prostate cancer and a number of people are do that along those lines they've had somebody they've either had cancer themselves or somebody they loved had cancer and they want to put money into cancer research bill gates on the other hand I think when he had got his fortune I mean he thought about it and felt well how could he have the greatest impact and he thought about you know helping people in the developing world and and and and medicines and different things like that that like vaccines that might be really helpful for people in the developing world and and so so I think first you start out with that vision once you start out with that vision whatever vision it is then I think you try to ask the question who in the world does the best work if that was your goal I mean but you really I think have to have a defined vision vision first yeah that that comes and and and I think that's what people do I mean I have never seen anybody do it otherwise I mean and and that by the way it may not be the best thing overall I mean I think I think it's good that all those things happen but you know what you really want to do and I'll make a contrast in a second in addition to funding important areas like what both of those people is to help young people and that they may be at odds with each other because a farm or a lab like ours which is you know I'm older is you know might be very good at addressing some of those kinds of problems but you know I'm not young I trained a lot of people who are young but it's not the same as helping somebody who's an assistant professor someplace so I think what's I think been good about our thing our society or things overall or that there are people who come at it from different ways and the combination the confluence of the government funding the certain foundations that that fund things and other foundations that you don't want to see disease treated well then they can go seek out people or they can put a request for proposals and see who does the best you know I'd say both David Koch and Bill Gates did exactly that they sought out people most of them you know or what are their foundations that they were involved in so I doubt people like myself but they also had requests for proposals now you mentioned young people and that reminds me something he said in an interview of written somewhere that said you're some of your initial struggles in that terms of finding a faculty position or so on they eat in quite for people fit into a particular bucket a particular right can you speak to that how do you see limitations to the academic system that it does have such buckets there's is there how can we allow for people who are brilliant but outside the disciplines of the previous decade yeah well I think that's a great question I think that I think the department has have to have a vision you know and some of them do every so often you know there are Institute's or labs that do that I mean at MIT I think that's done sometimes I know annika engineering department just had a search and they hired geo Traverso who was one of my he was a fellow with me and but he's he's actually a molecular biologist Anna and and a gastroenterologist and you know he's one of the best in the world but they but he's also done some great mechanical engineering and designing some new pills and things like that and they picked a man boy I give them a lot of credit I mean that's that's that's vision to pick somebody and I think you know they'll be the richer for I think the Media Lab is certainly hired you know people I get Boyden and others who depth on you know very different things and so I think that you know is that that that's part of the vision of the leadership who who do things like that do you think one day you mentioned David Koch and cancer do you think one day will cure cancer yeah I do I mean I coached one day I don't know how long that they will come soon but yeah so soon no but I mean I think do you think it is a grand challenge it is a grand challenges it's not just solvable within a few years not so I don't think very many things are solvable in a few years there's some good ideas that people are working on but I mean all cancers that's that's pretty tough if we do get the cure what will the Cure look like do you think which mechanisms which disciplines will help us arrive at that cure from all the amazing work you've done as touched on cancer no I think it'll be a combination of biology and engineering I think it'll be biology to understand the right genetic mechanisms to to solve this problem and maybe the right immunological mechanisms and engineering in the sense of you know producing the molecules developing the right delivery systems targeting it or whatever else needs to be done well that's a beautiful vision for engineering so on a lighter topic I've read that you love chocolate and mention two places venom Bill's chocolate thorium and the chocolate cookies the the Soho globs from Rosie's bakery Chestnut Hill I went to their website and I was trying to finish the paper last night there's a deadline today and yet house wasting way too much time at three instead of writing the paper staring at the rosey breakers cookies which or just look incredible the so whole globs just look incredible but for me oatmeal white raisin cookies it's not one my heart just from the pictures do you think one day we'll be able to engineer the perfect cookie with the help of chemistry and maybe a bit of data-driven artificial intelligence or is cookies something that's more art than engineering I think there's some of both I think I think engineer will probably help someday and what about chocolate same thing same thing you have to go to see some of David Edwards stuff you know he he was one of my postdocs and he's a professor at Harvard but he also started cafe arts sciences and you know it's just a really cool restaurant here but he also has companies that do you know ways of looking at fragrances and and trying to use engineering and in new ways and so I think that's just an example but I expect someday that AI and engineering will play a role and almost everything including creating the perfect cookie yes well I dream of that day as well so when you look back at your life having accomplished an incredible amount of positive impact on the world through science and engineering what are you most proud of my students you know I mean I really feel when I look at that I mean we've probably had you know close to a thousand students go through the lab and I mean they've done incredibly well I think 18 are in the National Academy of Engineering 16 and the National Academy of Medicine I mean they're you know they've been CEOs of companies presidents of universities I mean and Dave I mean they've done I think eight or faculty MIT maybe about 12 at Harvard I mean so you know it really makes you feel good to think that the people you know they're not my children but they're close to my children and in a way and you know makes you feel really good to see them have such great lives and them do so much good and be happy well I think that's the perfect way to end it Bob thank you so much for talking it was an honor good good questions thank you thanks for listening to this conversation with Bob Langer and thank you that sponsors cash app and master class please consider supporting the podcast by downloading cash app and using collects podcast and signing up at masterclass comm / Lex click on the links buy all the stuff it's the best way to support this podcast and the journey I'm on in my research and startup if you enjoy this thing subscribed by YouTube review it with five stars and half of podcast supported on patreon or connect with me on Twitter and Lex Friedman spelled without the e just Fri D ma N and now let me leave you some words for Bill Bryson in his book a short history of nearly everything if this book has a lesson is that we're awfully lucky to be here and by we I mean every living thing to obtain any kind of life in this universe of ours appears to be quite an achievement as humans were doubly lucky of course we enjoy not only the privilege of existence but also the singular ability to appreciate it and even in a multitude of ways to make it better it has talent we have only barely begun to grasp thank you for listening and hope to see you next time you