[Applause] [Music] [Applause] [Music] conversations with Tyler is produced by the mercada center at George Mason University Bridging the Gap between academic ideas and real world problems learn more at arcades.in conversations withth tyler.com [Music] I'm here today with Ed boen who is a
famous neuroscientist at MIT there is much more to say about him but he'll do some of that explaining himself before we get to what you've done let me just toss out a few general questions that the audience might be interested in if I were to read all of the good popular
books on brain science what is it that I'm still most likely not to understand I think something that people don't appreciate is how little we know about the brain so if you think about brain diseases you know like Alzheimer's and Parkinson's and Epsy basically none of these can be cured and
the treatments if they do exist are very partial and have a lot of side effects and similarly we we don't actually have theories detailed knowledge enough to make predictive interesting models for example of how we form emotions of how we make decisions so I think that uh you
know I sometimes half jokingly say we should write a book about the brain called ignorance what we don't know about the brain not sure how many copies it would sell though if I think about mental illness it seems that it's hard to find chemical correlates for mind states that would normally be counted as
mentally ill is that part of the puzzle how does mental illness show up in the brain do we know anything about that well this is a big mystery so there are two issues which which really need to be addressed so one is that mental illnesses for the most part are defined
by the symptoms I have a lack of appetite I feel apathy I don't feel pleasure in things that I normally do take pleasure in and then the chemical side is also a bit murky you know if we think about pharmaceuticals to treat brain conditions you know it's bathing the brain this complex wired circuit in
a substance and so of course it's going to affect parts of the brain that you want to change as well as parts of the brain that you'd rather leave alone so I think part of the problem is we need to Define brain conditions in terms of the underlying wiring and circuitry and so
most of the Technologies we build are oriented around two classes of approach one is can we make maps of the brain you know detail maps of the wiring if you will of the brain and the other is can you watch and control the highspeed Dynamics of the brain in other words can
you watch the brain in action and then perturb it so that you can heal the brain by speaking the natural language of the brain which is electrical pulses so let's get to optogenetics which you just mentioned if I understand this correctly you can in essence turn on lights control a mouse and make the
mouse run in circles is that an oversimplified account of what you do that's correct well I think it's important to point out the goal so the goal here is that if you could precisely control neural activity maybe you could actually repair a brain or discover the principles of how to repair the brain in
order which could inspire better drugs or better non-invasive brain stimulation methods so what we do is to speak the natural language of the brain which is electrical pulses we borrow from the natural world effectively tiny solar panels that exist in bacteria and
plants and those are arons right or algae yep so algae have these ARA have them yep y so these uh they make these little molecules proteins that convert light to electricity we transplant them into brain cells and then we can control the electrical pulses of brain cells
with light and what's the delivery method for the transplant that's viral well this is where we got really lucky so it turns out that these solar panels are actually proteins and proteins are encoded by DNA so you can use all these tricks from gene therapy to deliver the
gene into the brain and then it'll make the product this little protein encoded solar panel so what are the activities right now you can make the mouse do well we've given the Technologies to thousands and thousands of research groups at this point so people have been using the techniques to study even very
complex things like memory or aggression or complex emotions one of my favorite studies was done by du Lynn and David Anderson and colleagues they took our a molecule that lets you activate neurons with blue light and they put it into a region of the brain deep deep in the
brain and then they implanted an optical fiber connected to a laser and aimed the optical fiber at this cluster of cells now what happened when they turned on the laser these cells were activated and this was done in mice the mice would become aggressive or violent they would
attack whatever was next to them even if it was a rubber glove and so what I like about these techn IES is we can start to ask questions about you know why does the brain do what it does you know what is the nature of something like a decision or an emotion or even something like aggression or violence where you
know it has ethical implications so to be speculative it might someday be possible that you could fix somebody's Alzheimer's by showing them a movie well so this is an interesting uh you know I think of optogenetics as a tool for discovering how to repair the brain but
then you can build very practical Technologies to try to help people and so my uh collaborator leeway Sai led a project where she used our optogenetic tools initially to discover a pattern of brain activity that in mice engineered to get the symptoms of Alzheimer's disease it would actually make them
better and then the teams went on to actually discover that through a movie a bunch of blinking lights and and so forth you could simulate the same pattern of activity so leeway and I have now co-founded a company Cognito Therapeutics to effectively do human Trials of movies to treat Alzheimer's
what's the most likely therapeutic application that might come next um out of optogenetically inspired discover yeah yeah well there's a lot of people who are uh discovering regions of the brain that you can modulate to shut down for example epileptic seizures uh people
have found that if you stimulate the brain in certain patterns you could actually help with parkinsonian symptoms again in mice and again it requires a gene therapy which is expensive to deploy to humans but if you use the information they've gotten by studying Parkinson's and epilepsy in mice and
then try to build non-invasive ways of controlling the brain to repair it I think that could translate to humans quite rapidly and so in my GR group uh near Gman who is then a postto in the group we actually found a way to focus the effects of electricity deep in the
brain from the outside so imagine now that we use optogenetics to discover a pattern of activity and then we try to induce it through non-invasive means like watching movies hearing sounds focusing electricity from the outside and so forth I think that could be a
pretty good pipeline for the future another area where you've had major contributions is expansion microscopy what's your basic explanation of what that does well for 300 years people have been trying to zoom in into biology you know lenses to see bacteria and then about 100 years ago people started
finding out about brain cells and other interesting things but there's a problem you can't see things much smaller than the size or wavelength of light and light has a finite wavelength of a couple hundred nanometers now that might sound small but biomolecules are much
smaller they're a couple nanometers so they're like 100 times smaller than the the limit of a microscope so there are tricks you can play a bunch of people won the Nobel Prize a couple years ago for inventing super resolution microscopes which are very accurate but they can be expensive and slow and
they're hard to use to image three-dimensional objects so in my group we often start by trying to think about can we do the opposite of what other people have done and so we started thinking what if we instead of zooming in like they've done for 300 years let's blow it up and so two uh then gr it's
like you inflate a part of the brain exactly and then it's easy to look at yeah so two then grad students fate Chen and Paul tilberg in my group we decided what if we could take a piece of the brain preserved of course these are not living brains and we Infuse the
specimens with the same kind of chemical that you find in baby diapers a swellable polymer and if you do it just right and you soften up the brain so that it doesn't resist the uh the forces that you're going to apply Add Water the diaper material swells and the Brain
will become bigger by like a 100 times or or 10,000 times in volume and so it turns out we discovered that you can the process is very even it preserves the information of how the molecules are organized it's just bigger and that can help us make maps of the brain that's right so now we've actually taught
hundreds and hundreds of research groups how to do this and we ourselves are trying to use the technique to make entire maps of initially small brains you know like fish and flies and worms and so forth but if it works well we want to scale it up to Maman brains like
mice and then to human brains if we can make a map of the brain so detailed that we could simulate decisions or emotions in silico in software I would be very excited about this because it would kind of tie into my own desires for Neuroscience which is to understand something deep about The Human Condition
but also the practicality of it is that we can make very detailed maps of the brain and figure out where diseases begin and when you say maap you mean computational device or is it in some more literal sense a map well so brain circuits are very densely wired electrical circuits so a brain cell will
have electricity flow throughout and then brain cells have connections called synapses which exchange chemicals and in a cubic millimeter of your brain you have about 100,000 brain cells with with about a billion connections between them so how are they wired up that would give
you a big clue about what the computation is that's occurring how does the information flow and how is it transformed so what we want to do is using our expansion Technique we want to make a map of the brain which literally would tell you where the wires are and how they're connected to each other but
also which biomolecules are on those wires are some connections fast are some slow are some strong are some weak to tell those things we have to know more than the shape of the cells we have to also know where the molecules that do the business of the neural computations
where they are located as well let me ask you some questions about brains I would like the answers too go for it some of my more science fiction oriented friends speculate about whole brain emulation that someday an entire brain or something like the brain could be uploaded into a computer and people
would live forever in some different form how plausible an idea is this well if we had a detailed map of the wiring and also we could locate and identify where the key biomolecules are I wouldn't be surprised if someday we can make a biophysically accurate simulation
in a computer in fact for very small neural circuits like in the Crabs St metag gastric ganglion Eve marter at brandise already has been able to do biophysically accurate human understandable simulations so then the question though is would the computer feel like it is you or you would have a
simulation that would simply predict what you Ed boen would do in some situation so that's a big question isn't it and I think the honest answer is since we don't know what Consciousness is right you know you don't even know for sure if I'm conscious right maybe
I'm just a very accurate robot that's sitting here while my true self is lying on the beach somewhere soaking up the Rays that's kind of the big open question you know there's no consciousness meter that says oh that being is a conscious being there's no way to create Consciousness from scratch
as far as we can tell so I think one of the things we have to figure out is how can you detect Consciousness and how can you create Consciousness you know Alan Turing proposed the Turing test where you would converse with something and you could try to decide whether it's
conscious but you know with Siri and Alexa and all this stuff in homes and on phones nowaday I think everybody would agree that's probably not enough you need to know something about the internal State as well but we don't have a firm grasp on that yet do we know much reliable about LSD in the brain there
are some papers claiming LSD limits depression should we trust those papers do we know nothing you know that's not my area of expertise I mean personally I think that there's a lot of interesting questions about how chemicals modulate brain circuits and psychedelics and lots
of other chemicals uh could have interesting effects so one of another psychedelic drug ketamine which causes inations has actually been seeing a lot of Trials recently for its uh effects on rapidly helping depressed patients feel better so most anti-depressants take 3
weeks or more to help people ketamine happen uh will help within you know uh tens of minutes to hours so that's an example where a helicogenic drug can actually have a rapid acting effect on a psychiatric illness I wouldn't be surprised if there are other interesting findings that could be brought out of
this but I'm not an expert on that area unfortunately is meditation effective I person find it effective I meditate every day and I've been practicing a form of internal family systems uh meditation where you kind of treat the parts of your mind like members of a family and show compassion for them and
thank them and and love them and they relax and become you know more of your Ally and I've done this uh about 10 years now 2009 my land lady in Pao Alto when I was a grad student at Stanford taught me about it and took me a while to actually get going on it but uh yeah
I find it transformative because the parts of your mind that might be driving you anxious or causing despair you realize what they're trying to do for you and you by loving them and showing gratitude to them can make them you know on your team rather than trying to rebel
against you how much of that do you think is Placebo value which would be fine right placebos may be underused in medicine it's a good question um I think that there are a lot of different ways of trying to confront um you know everyday stressors that cause anxiety or Despair and so forth for me I played
with a lot of different strategies including other kinds of meditation that aren't so focused on the parts of your mind and to be honest I felt relaxed after doing those kinds of meditation but I didn't feel like the parts of my mind were becoming allies so that was unique with me anyway and other people
might differ but with the ifs method are we less creative if all the parts of our mind become allies maybe I'm afraid this will happen to me that I have rebellious parts of my mind and they force me to do more interesting things or they introduce Randomness or variety into my
life yeah and this is a question I think that is going to become more more urgent as neurotechnology advances so already there are questions about attention focusing drugs like rlin or Aderall maybe they make people more focused but are you sacrificing some of the
wandering and creativity that might exist in the brain and be very important for not only personal productivity but the future of humanity and I think what we're realizing is that when you intervene with the brain even with brain stimulation uh you can cause unpredictable side effects so for
example there's a part of the brain called the dorsal lateral prefrontal cortex and that's actually an FDA approved site for stimulation with non-invasive antic pulses that treat depression but patients when they're stimulated here people done studies it can also change things like trust it can
change things like um driving ability you know so you know there's only so many brain regions but there's millions of things we do of course intervening with one region might change many things there's an old saying that we quote unquote think with our gut do you attach
any Credence to this is there some broader process of computation going on we think it's not just in our brain well we've now realized as a community my group doesn't work on this yet but it's a very exciting area that the brain is almost like part of an ecosystem that
you could call the body and the whole body is Computing together so maybe over the time course of several seconds when you have an individual thought or feeling maybe a lot of that is contained within the brain but if you go beyond that time scale you know there might be microbes in the gut that secrete
molecules that can actually get into the brain and modulate you know complex functions like maybe even social Behavior some people think does that mean whole brain emulation is impossible then you basically have to reproduce the body well it's a good question one
possibility is that if you are emulating the brain maybe you can run the simulation for a short period of time but if you want to integrate all the changes that are du to the rest of the body to Encompass more complex things like long-term emotions or moods you might call them or you know memory or
personality you might have to think about um the body as an ecosystem and then there's also the concept of extended intelligence where you know I'm not just me you know if I'm getting out of bed in the morning and getting dressed and having a cup of coffee you
know that's one version of me but then you know when I get up on a stage to lecture for my class or if I go and and hang out with friends you know maybe certain parts of my personality are expressed in other parts or not and I think we all experience this all the time where you know we're part of an
ecosystem of people as well so I think what's going to happen is we're going to need to be able to simulate as much of the biology is possible and then there might be a point where things kind of become unpredictable you know what do we need to to know next do we you have to
map out the structure of human interactions as well if I think about memory is it possible that is more than just sinaps connections that there's some kind of RNA based calculation supplementing what we normally think of is memory how well do we understand memory well I think what we have learned
from the history of biology is that if a biological system could use some biological resource to get something done it will and so you bring up the question of RNA you know brain cells have one nucleus with the genome inside but thousands of synaptic connections so does it make sense to only have genes
on or off at the nucleus level you might want to turn genes on or off at the synapse level and so one of the things actually that our group published a couple years ago is a technology uh a version of expansion microscopy where we could actually try to map out which
expressed genes are located at which synopsis we can take a braid and blow it up and then look at where the the expressed genes are cached or stored throughout the brain cell so now several groups are are I think using such Technologies to try to map out whether indeed all the different biomolecular
types are involved with plasticity so it's kind of early days um but previous uh groups um before we even unveiled this technology had found some evidence that when you activate a brain cell interesting transcriptional spatial changes occur in fact one of my favorite
studies was done by a group in Utah they found when brain cells are active they turn on a gene and it this Gene looks a lot like the coat protein of the HIV virus the same virus that causes AIDS and maybe even more amazingly when a brain active it manufactures virus-like particles that can bring genetic
material from one brain cell to another so it's kind of wacky to think about it you know when you actually put your mind to it when you're forming a memory is your brain manufacturing HIV like things and you're exchanging genetic material from one brain cell to the next what the
heck is going on but I think that just shows how little we know about the mechanisms of brain function here's a real soft ball of a question is consciousness a fundamental feature of the universe or an illusion is metaphysical dualism true ah well do how many hundreds of years do
we have for this conversation what's where do you stand now let's start with that okay no one knows right but you must have an opinion of some kind well I try not to have opinions but I do try to think about uh which I know is impossible but I do try to think about the approach that one
would could take because I'm an engineer at heart and then the question is what can we do about it and so here's one thing I've been thinking a lot about suppose that at a certain moment I am conscious of something and my brain has a certain state presumably that brain state was caused
by a previous brain State and during that previous brain State we were not conscious otherwise we would we would have call that the conscious experience so one reason why I'm so focused on brain circuit mapping is if we could catch the brain circuit in action as a
conscious sensation or feeling comes into fruition maybe we can understand the process of Consciousness and so maybe that would give us a clue about what Consciousness is because we can understand how it arises so this is a very early stage way of thinking about
the problem and we don't have any data yet really but there are other people who have actually done some cool experiments um like Benjamin leet and John Dy and haes and others where they ask people to whenever they want move their hand or do some other task and then they image the human brain and they
try to figure out what areas of the brain are active when people feel like they are making that decision and they can actually detect changes in the brain up to 10 seconds before people feel like they're making the decision to move their hand so that's a clue that maybe
you could try to understand the process through which something comes into conscious awareness and if we can map out the detailed circuitry you know the electrical wires and the molecules along those wires that yield that maybe we could actually try to simulate it in a computer but this is a very early stage
way of thinking about it ultimately do you believe in reductionism that what is the brain can be understood by physical science and by materials and by cause and effect the way we we would understand say a computer um well if you say can we understand the brain in terms
of chemical underpinnings I would say yes and Consciousness well so again I think we don't have a good definition of Consciousness in the sense that we cannot detect it through a Consciousness meter and we don't have a creation Method Of Consciousness engine so the jury is still out on that front but I
hope to study it you know science can fail you know there are certain things that science can't yet answer like what happened before the Big Bang and so forth but I think we have to give it our best shot Derek parfett argues that perhaps we're not even a single person so he cites split brain experiments
where in essence one brain turns into two and you can then ask which is the real person do you have a view on the meaning of split brain experiments do they teach us anything oh I think this is fascinating and you know AI Pioneers like Marvin Minsky you know wrote about
the Society of Mind about this idea that your brain is a bunch of independent agents that can work together in the form form of meditation that I practice this internal family systems model you actually do explicitly try to consider parts of your mind as having their own
drives and their own wants and their own plans and that helps you you know understand them and a way but is there a central you behind all the different wants and desires is there a puppet master in the theater the or is it a a kind of nominalist reality where all there are the different desires and
maybe the film involves a kind of Illusion that someone's in control but that's just another actor in the play well here's another way of looking at it which is you know there's so many things that we're consciously aware of but the vast majority of the things that the
brain is doing we're probably unconsciously aware of right so for example you know here we are in my office and there's all sorts of stuff around um and your brain has been processing a lot of it and so if I point at that blue highlighter over there you'll you probably saw it earlier but
we're not paying conscious attention to it but now that I point at it you you were consciously aware of it so I actually think that something uh that we have to understand is how are all these unconscious processes this roing sea of stuff that we have no access to how are
those processes contributing to the emergence of Consciousness and that's one reason why I'm very excited to study the process of Consciousness if you will what are the processes in the brain that lead to it that happened beforehand and that might help us understand in a causal way what gives rise to
Consciousness but again this is just an idea right now let's say we can can extend innovations that allow brain signals to be used to control the physical world so I can think of something and a cursor moves on a computer screen just selfishly which innovation would you find the most use
that you could sit here in your chair think of something and it would happen someone a robot brings you coffee what is it you want not as a scientist as a person great question well I mean the the thing that got me interested in you know confronting philosophical questions
through science as a kid was about human suffering I guess i' would want to way for to help make empathy possible so right now it's very hard to know what somebody's feeling in their mind we use language to try to convey that but it doesn't quite seal the deal right that's
one of the reasons some people think why there's so much conflict that you can't understand the internal state of somebody else at a at a true level so what if I could read out what happens in my mind and somebody else could experience that literal State and vice versa this is something I've been
thinking a lot about that I would like to work on in the long term um but uh obviously has a lot of basic research to go into before we're even close to ready for that I worry sometimes that would make things worse so I think if people on Twitter they see what each other have
to say they like each other less there's some partial evidence that if you try to mentally put yourself in someone else's shoes you realize that what they think inflicts with your values you may be less inclined to agree with them is it possible we have too much empathy and we should just be more objective more Spock
and rational calculators well it also might be that we have to think of empathy in in a new way so now as we talked about earlier suppose that what we are consciously aware of is being generated by some unconscious unconscious processes that happen right beforehand maybe when we are trying to
experience empathy at a certain point in time there are other processes in the brain that occurred beforehand that we don't have access to but if we could access those processes we could have a greater kind of empathy and some of this language is used in meditative and
Consciousness oriented and mindfulness practices that try to understand compassion and empathy in a greater way but I wonder if there's a precise neuroscientific way to tackle such things there's a report from about 5 days ago that there's a new cont contribution coming out of Colombia for
a kind of mind vocoder they called it I believe almost a kind of mind reading that you can read mind signals and have some notion what an individual is thinking you're familiar with this work um I've been so focused on writing manips the last couple days that I haven't I don't know stuff in the last
couple days in in the scientific literature but the idea is conceivable to you oh yes yes groups for many years have been using uh functional MRI a kind of brain scanner to read out what people are uh are seeing uh so you can show somebody a movie scan their brain and
you can statistically guess what they actually are seeing so that's been that's been well known and many groups now have been refining this kind of approach so it sounds like this group has made an advance in that area what's your biggest worry as to how this might be used in the future well neurot
technology in general I think presents a lot of ethical implications that um I think we need to proactively start discussing and start self-regulating and start making people aware of and I think part of the problem is that people I think often don't feel comfortable talking about
their brains I was on a panel once at a conference where the chair of the panel asked the audience how many of the people in the audience had used a a cognitive enhancing drug and nobody raised their hand and then the chair of the panel said um you know what probably
20% of you should have raised your hand because they had done an anonymous poll earlier of a similar population and so I think there's a stigma about talking about the brain I almost feel like we need a new language you know I want to talk about me but I also want to talk
about my brain is there a new word which combines both of those words so that I don't have to talk about my brain in a dehumanizing sense I also think we need to start getting um neuroethics on the table you know we just all heard about the crisper baby debacle uh in China and
and now of course there are lots of people making statements about you know we shouldn't do that in neurotechnology can we get out ahead of the problem before it happens by working together and coming up with guidelines of what we want to do and what we don't want to do
and maybe some things we want to do but it should be you know thought about in detail by an objective or at least as objective as possible panel that's not connected to the work and so forth so I'm talking to people now about what if we could get maybe um a global neuroethics conference going which would
bring together the companies and the scientists the investors and the governments religious leaders and lawyers and you know people with stakes in different parts of this um and to you know get that going before you know is you know headline news that we don't necessarily appreciate but it's
self-regulation or even public regulation a kind of myth so maybe the innovators just always move more quickly than councils or bureaucracies so standards tend to be set by groups groups are relatively slow they're reactive so I know people who work on algorithms they work on uh you know
credit scores and they've had these same conversations and we wake up one day and China has a social credit system which they use to control people and it just happened and we condemn it exp poost but isn't that the most likely course for brain science that a bunch of things
will just happen many will be very good some will be bad and we won't really have much of a say at the regulatory level and there are many countries right well that's one possibility but if you look at the history of biology around 1975 or so Paul Berg who won the Nobel Prize for his work in Biochemistry
convened in aamar California a bioethics conference about because this is the dawn of gene cloning making transgenic organisms that have genes that shouldn't be there it was a period of great distrust in political systems maybe not unlike our time in a way as well and um
they decided to actually get together and figure out how to self-regulate and regulate uh molecular biology and so now half a century later you know uh this has yielded a lot of you know huge benefits to human health and for the most part they've been able to proactively discuss things and it's not
perfect of course but I think one can try to take action doesn't guarantee Perfection but we can certainly put our best efforts forth would it be good if we had a fairly accurate lie detector it could read your brain waves maybe the tone of your voice the your micro Expressions but it would be able to tell
if you're telling the truth or not and you wouldn't even have to consent to be hooked up to it so you'd go out on a date you'd turn on your lie detector it would give you feedback throughout the course of the date is this a net social good if it's bad do we have a way of
stopping it that's a good question yeah well I think there's a lot of um questions about lies and and memories that are that make the question very nuanced so for example there's a field in memory research where they look at what's called reconsolidation what happens is basically when you recall a
memory it becomes fragile and there are now studies about how even false memories can you know induced you know they've done an experence where you show somebody something in a photograph or in a story and then a week later you asked oh how is your experience and it wasn't their
experience it was in a photograph or a story and some fraction of the people will remember it as their experience so I think if we start thinking about you know these kinds of topics that connect to Everyday Human Experience like lies and memories and so forth I think we
also have to delve very deeply into the underlying Neuroscience so we know what we're talking about and what we're doing so for example if somebody talks about something uh in a certain way but you know it was not an intentional lie it was a false memory you know what are the
subcategories of different things that people say and what about things that are coupled to external influence like the example I just gave where the memory was affected by an external photograph or story so anyway I think that we have to make sure that the science
accelerates as fast as the technology you know sometimes say that the hard part of neurotechnology is the neuro part maybe we'll have the ability to scan brains and read out information with unprecedented accuracy at some point in the future but if we don't understand the underlying processes and
what the information means then we might do the wrong thing with that information in the middle of all these dialogues we have a segment overrated versus underrated and I'll toss out a few names of things and you tell me what you think you're free to pass on any of them uh
waking up at 4:00 a.m. in the morning underrated or overrated well I do that myself I I go to what's the advantage well for me I um I get four or five hours of time to think and write and uh without you know constant barrages of people emailing me and knocking on my door and so forth so I really value
value that time the downside is maybe a a less adventurous social life since I go to bed at you know 8 or 9 at night but people who want to work more should do it um I don't think I work more I mean I'm getting up early but well you're interrupted less right um well it
depends on what your goal is I mean there are certain parts parts in a project where I need to be interrupted a lot because I'm putting together lots of ideas or connecting lots of people to form a massive collaboration you know we just published paper on applying expansion microscopy for whole brain
mapping a CP couple weeks ago it has a zillion people on this this paper and a lot of people contributed ideas and techniques and so forth so it kind of depends on I try to think backwards from problems and then use that to derive my path as much as possible it's not an
exact science but the more I can understand my goal and use that to frame my Approach uh the better it can be so there are times in my life when I give up this schedule you know if if I'm at a conference and the the exciting discussions are happening late late at night I'll actually switch bird song as
music overrated or underrated oh it's funny you bring that up cuz um working on bird song as a neural circuit problem was my very first Neuroscience experience in 1998 yes and uh I worked on zebra finches which are not famous for having a particularly sweet bird song but there are there's certainly a a
wide variety of of other species that I think have more appealing songs but uh uh yeah there's a lot of species specific stuff out there and um you know uh parrots of course can emulate human speech and mocking birds can pick up all sorts of interesting patterns from their
environment and I think one of the things that I really love about um the space of ecological diversity is if you think of brains as Computing things then ecological diversity might provide many ways of computing the same thing but in different ways that actually yield
interesting computational insights or aesthetic outcomes like octopuses oh octopuses are very interesting yeah yeah and dolphins of course also have a unique form of intelligence is pretty clear yeah the list goes on and on about ways that brains solve problems or create things and it's just amazing the
the the sort of evolutionary uh set of possibilities out there that remain to be explored now you've won a $3 million breakthrough prize are using prizes for science is that underrated or overrated should we do it more that's a good question so I think of prizes as a way of Storytelling it's a way of
celebrating an achievement that makes it accessible to a broader audience but you also don't have to pay out to losers right so you can save resources well on the other hand I think that if you look at how science is evolving with more and more collaboration and and longer and
longer time scales one of the issues is that uh the number of people people who contribute it's getting larger and larger so you've probably seen all these controversies with crisper for example right with the the list of people who you know they some people discovered
crisper and then other people figured out how it works and still other people figured out that the way it worked was modular and therefore programmable and then still other people applied it to human cells and so it's a long list of of people know what if we could tell the
whole story in a way that um allows it to be appreciated in in a a broad audience fashion so part of me often wonders about you know storytelling as a modality for for conveying the value of science um but the idea that you should limit it to a small number of people I think is partly because of this this
limitation that you know we it's hard to understand a story with 100 characters neuroeconomics overrated or underrated that's a good question so I don't know much about neuroeconomics I mean most of my work is at the the circuit level looking at very small circuits on the
other hand I think that anything that Advan is a study of human behavior given its murkiness and complexity you know is much to be desired and I'm I'm starting to meet people in this field now and it's quite exciting the idea that you could actually make a prediction about
human behavior based upon some kind of insight that's mathematically extractable from prior prior Behavior or from brain Imaging I mean uh this this Free Will experiment I mentioned earlier where you can predict somebody's Behavior you know 10 seconds later uh by looking at what their brain is doing now
I find such things fascinating Archimedes overrated or underrated comdes um well I don't know the details of of who he worked with and and how they all contributed to each other but certainly you know the the famous you know stuff that he did in terms of aredes principle and the stuff that he
innovated and and discovered you know stands the test of time I guess the big question is you know if you actually were there and saw what people were doing what happened at you know in the trenches right and uh again it boils down to some of these might have had
many collaborators exactly and again you know we the story of science you know as especially in this uh sort of prehistory era where documentation was not as good as it is nowadays you can't just you know Google all the things aredes wrote down you know day by day and hour by
hour you know we have these fragments of story um it's hard to know but certainly the accomplishments of you know that have yielded Untold insights into physics mathematics and all sorts of stuff do you enjoy seeing Frank Gary buildings every day when you go to work in the morning I do like that building
yeah so I parked my car in the basement of that building and when my kids were there for daycare they would they would I spent a lot of time in that building and I I do like it I think architecture is very important I find architecture to be very inspiring for scientific
scientific ideas and so my group started out at the MIT media lab and now we have half our group over here in the MIT mcover Institute but I I like I used to wander the halls of Campus late at night and just look at stuff posters in the hallway and and get inspiration by
trying to connect dots from different fields or disciplines or even entirely separate unconnected topics and I find a lot of productivity from inspirational environments and connecting dots between random things if you're designing architecture for science what do you do what do you change what would you
improve because presumably most of it is not designed for science maybe none of it is well I've been thinking about this a lot actually lately I think you know there there are different philosophies like we should have open offices so everybody can see and talk to each other
or that's wrong you should have closed spaces so people can think and have quiet time and what I think is actually quite interesting is um this concept that maybe neither is uh the right approach you might want to think about having sort of an ecosystem envir of
environments so in my group we're partly over at the at the media lab which has a lot of very open environments and our other part of the group is in a classical sort of Neuroscience laboratory with offices and you know small gr rooms where we park microscopes and stuff like that and actually get a
lot of productivity out of switching environments in a deliberate way I do the same I might add now you were first tired here by the media lab is that correct I was so they were a different ecosystem and they saw some reason to hire you where other grp groups were didn't see the same reason yeah well I I
was ready up these faculty applications to propos to set up a a full-time neurot Technology Group let's control the brain let's map the brain and uh yeah at the time the majority of the places that I applied to for faculty jobs they actually turned me down and so I went to
the media lab to talk to people there um I'd been an undergrad researcher there that's when I was doing work on Quantum Computing for example and it was just sheer dumb luck they had a job opening that they couldn't fill and so they said why don't you apply a job opening for
what I can't recall the details it might have been a professor of Education or something I forget what what it was but but they said you know what you the media lab maybe our new mission is to hire Misfits so in the old days of course the media lab did you know media
and right but now media is everywhere right and so a lot of the the newer hires at the MIT media lab are working at the intersection of a life science and some other kind of science like Kevin esfeld who's trying to build crisper genan drives to edit ecosystems it also thinks about the ethics and the
politics and the sociology right so it's um it's a great place for people between one field and another where there's sort of some space but you know what it could be an entire new discipline and now Flash Forward 12 years later you know we actually started a center for neur
engineering here at MIT that I co-direct and is it correct that you also teach in the business school or you have why do you do what do you do and why do you do it well many many years ago when I was a student at MIT uh yo sponson who was then also a student and I were
brainstorming about an an idea about uh a neurotechnology class that would train people how to get ideas out of the lab and into the world so that brain technology is more than a list of Publications it's going to eventually become you know initially tools for say the scientific Market but later tools
that could go to the medical market and maybe eventually tools for the consumer and so um one of the first things that we did when I got back to MIT as faculty was to start a class with the MIT Sloan School of Management and also a bunch of scientific engineering and other departments it's cross-registered
amongst all these different schools here which is about that very topic neurot technology Ventures and so um we brought in the class to call it uh revolutionary Ventures because we realized that a lot of the ways we thought about neurot technology could apply to other fields
that could also benefit from a big jolt in the arm like alternative energy or other parts of healthcare and so forth and so uh yeah we have about uh 30 students or so take the class each term and we teach it every fall what is it you learn from your business school
students that you don't learn from your science students well I try to learn from everybody I I I I don't but it's different things right well I think I learn more different things from different individuals then from the categories of people because some of the people who come to take the class are
you know they might have been an executive in a big company before and I might learn something very deep about you know um how to lead a team uh where somebody who is a new business student or even a business undergrad um might have uh some untested ideas but not that
you know uh deep bench of experience that a a seasoned executive would so I think I learned more from individuals uh and their variability from then from categories of people for example in our group at MIT uh I have two PhD students who uh neither finished College actually um I I can't think of any other
Neuroscience groups on Earth where that's true you know and you hired them I did yeah knowing they didn't finish college and that was a plus uh or I'll hire them in spite of this well it was uh one of them had been a teal fellow um and then uh decided that you know it
could be good to have an ecosystem in Academia to support you know a long-term biotechnology play it's hard to do biotechnology all by yourself and and then the other uh was a College Dropout who was working as a computer tech support person next door and yeah both of them are now leading very independent
projects so I think again I I try to look more at the individual and um I try to get to know people over a long period of time to learn what they're good at and how they can maybe make a contribution based upon their unique experience that's different from what people have done traditionally is there
a style of West Coast Science different from East Coast Science are there things you can learn better out there in California I think there's so much cross talk nowadays you know I I read a statistic that 40% of the professors at MIT trained at at one point in their
career at Stanford Harvard or MIT and so's a lot of cross talk that goes back and forth I think one of the themes in science is that you you end up um you know learning different things and bringing multiple things to Bear now um in terms of how the the the Venture Capital side of Science and the the
startup side of science though I think there might be some differences um but what would those be well that's a good question I mean I again this is not my area of expertise because I'm relatively new to entrepreneurship it's only over the past couple years that I've really
been pushing hard to starting companies but it does seem like there you know many East Coast investors are um like Third Rock Ventures for example they like to build companies bring together many co-founders and so forth uh maybe in the west coast there more of a you
know founding team let them drive it uh maybe investor more passive model again this is might be me new to this whole world but um but having now talked to a few people seems like there definitely differences in the personality at least on the investing side that's consistent
with my experience how should we improve the funding of Science in this country you know I like to look at the history of science to learn about its future and one thing I've learned a lot over the past couple years and it's even happened to me um is that's really hard to fund
pioneering ideas Brian kabila who recently won the Nobel Prize for solving the structure of the G protein coupled receptor um and for context you know like onethird of all drugs Target this class of molecule so it's a very very important class of drugs you know he lost his funding um because he wasn't
you know making progress fast enough if I recall he had to Moonlight as an emerging emergency room physician to keep going on his research you know Doug prasher who cloned the gene for green floresent protein which has been used in something like a million biology studies
ballpark you know he lost his funding and eventually left science and end up driving a a a shuttle bus for I believe a rental car facility or something anyway there's so many stories and for me it became personal because when we proposed the expansion microscopy technology where we you know blow up
brain specimens and other specimens 100 times in volume to map them people thought it was nonsense people were skeptical people hated it you know I I'm like nine out of my first 10 grants that I wrote on it were rejected and if it weren't for the open philanthropy project that heard about our struggles
to get this project funded um through again a a set of links that were as far as I can tell largely luck driven um you know maybe our group would have been out of business but they came through and gave us a major gift and and that kept us going so let's say you had 10 or2
billion do a year and you would control your own agency and you were starting all over again but current institutions stay in place what would you do with it how would you structure your grants you're in charge no board you do it yeah well three thoughts so the first thing
that I thought a lot about studying these past cases and then going through it myself is thinking about peer review so what is peer review well when you propose a project a bunch of your peers will then critique it and uh the problem that a lot of these daring sounding projects encounter is that they you know
they sound bad during peer review um and so because they're so off the wall or they you know they bring together multiple Fields so that maybe nobody's qualified to evaluate them and so one thought is what if instead of just instead of taking people's opinions and then just sort of combining those
opinions and then okay you're in or you're out in terms of getting the money what if we take a step back and we think about why the peers are thinking this way you know if somebody critiques a proposal but they're doing it from a vantage point that doesn't see a certain
part of The Proposal as valuable because they're missing an underlying piece of knowledge or they're evaluating a proposal based upon opinion but if we think about the logical underpinings of it the rationale is actually pretty solid in terms of its you know being
linked to ground truth of all Sciences like physics and chemistry in other words if we take a step back and apply more logical principles of evaluation to the outcomes of peer review can we actually improve the the ranking of these proposals so this is something I'm thinking a lot about right now I
evaluate people and evaluate ideas that people propose to me as well I'm trying to hone those skills in myself so that's one of the the three things I would do how much more productive could science be on a per scientist basis let's say you could redesign everything refereeing
universities how grants are made can we double the progress of science just boost it by 10% it seems science is slowing down in many ways so do you want me to answer that question or I have two short takes also about how Chang the funding and then get to that okay so just very briefly the second thing I
would do is to be more dynamic in my funding you know right now maybe there's a grant that you apply for and then a year later you get the money but what if you know somebody try something out one Friday afternoon and whoa that could cure a disease or that could yield an
amazing new insight into biology or that could you know allow us to diagnose brain diseases early or whatever why wait a year so what if one could dynamically allocate funding you know Up and Down based upon you know the the real-time metrics of Science in my own group you know sometimes we begin a
project out of the blue and hey that's pretty cool and then we'll dynamically try to understand if we can reallocate resources that's another thing I would do and the third thing I would do is I would go looking for trouble I would go looking for Serendipity you if you look
at crisper for genome editing that was found by some scientists working on yogurt if you look at flourescent proteins that was identified by a person who just was obsessed with jellyfish and in my own Fields you know if you look at our optogenetics work or our expansion crosy work these fields owe aept to
basic curiosity about you know Critters living in you know bodies of water for optogenetics and expansionary coloscopy goes back to the 1980s where people were wondering why do certain polymers swell so hugely with no practical purpose implications of it so one idea is can we
how do we find the the Diamonds in the Rough the the big ideas but you know they're kind of hidden in plain sight I think we see this a lot right machine learning deep learning is one of the hot topics of our time right but a lot of the math was worked out decades ago back
propagation for example in the 1980s and 1990s and what has changed since then is no doubt some improvements in the mathematics but largely I think we'd all agree better compute power and a lot more data so H how could we find the treasure that's hiding in plain sight
how do we and and so one of the ideas is to have sort of a swap team of people who go around looking for how to connect the dots all day long in these serendipitous ways does that mean fewer committees and more individuals um or maybe individuals that can dynamically bring together committees hey you're a
yogurt scientist that's curious about this weird crisper MC you just found here's some B fromat assist who are looking for to find patterns here's some protein Engineers who love but should the evaluators be fewer committees and more individuals so the people doing the
work will always be groups but committees arguably are more conservative should we have people with more dukedoms and foms they just hand out money based on what they think well Committee of of people who have multiple non-overlapping domains of knowledge could be quite productive you know what
if I brought together to evaluate a proposal and I have a physicist who can tell me you know what that amount of energy won't kill the brain and then I have a biolog says you know what that's a really important problem and then a chemist who would say you know what that
molecule probably won't be toxic you actually need a committee to judge some of these ideas is progress in science slowing down right now it's a good question I think what's happening is we're tackling bigger problems so let me explain what that means so in physics there's a small number of building
blocks like protons and electrons and a small number of ways they interact like electromagnetism and so forth uh chemistry there's more stuff there's um you know 100 odd things in the periodic table although maybe there's only like 30 to 50 that you actually have to work
with if you're trying to make something actually happen and again there's a small number of bonds you know Cove valent and ionic and so forth I think the problem right now is a lot of the scientific questions we're wrestling with whether it's in biology um and medicine but I'm not an expert in this
you know more about some of these things than I do but like in economics and education and so forth it also seems like there from my you know distant view some of these uh problems they relate to this idea that there's a lot of different building blocks in a lot of ways they interact so in biology we have
what 30,000 genes in the human genome and while we know their sequence for the most part we have no idea how these Gene products interact with each other and how they're architected into cells and tissues and organs and how those go wrong so the problem is this Comal
explosion of possibility is so staggeringly huge that a lot of what we try will fail and so what do we do about it well one point of view is well if we have better tools and we can map those building blocks and those interactions maybe we could reduce the risk of biomedical science and again it's it's
not my field you know more with us than I do we have to hear your opinion but in economics and in other fields it also seems like people are trying to make better maps of things and how they interact so that's one idea is you know what if we could make these problems you
know progress might seem to be slower because the problems are so hard but with better tools maybe we can level the playing field and make 21st century Sciences more tractable in the same way that 20th century Sciences gave us lasers and computers and the internet in economics we have more good empirical
papers than ever before but virtually no more theoretical breakthroughs and I'm not sure we'll ever have them again oh how interesting may just be diminishing returns there are so many fundamental ideas and you learn those and you stop and then you measure things well in biom
medicine you know systems didn't evolve to be understood they invol evolve to survive and reproduce and all that so one can hope for structure and every now biology does give you more structure than we deserve I think I mean DNA has a double helix and you can read out the
genetic code and so uh you know there's always this question of why is the universe understandable in the first place and maybe now we're entering the realm of complexity where things are less understandable but again you know we we have to accept reality for what it is so
one of my readers suggest that I ask you about quote the approaches to problem solving problem decomposition and backward chaining that he teaches his grad students on posts does that make sense to you it does tell us well two thoughts uh so one thought is um you know we're neurot technologist for the
most part we do some science but mostly technology so a lot of people of course are have built tools for biology over the years but not not all the tools have been equally useful so one of the things we do is to think backwards from a problem so that when we build the tools
we actually can solve the problem with optogenetics the problem was how do you control the brain to repair it with expansion microscopy the question was how do we make a map of the brain that's precise but scalable so Bing Backs from major problems is really really
important now how do you actually then do anything about it well the this uh one strategy we try to do is then I think of every possible idea of how to solve the problem so with optex my co-inventor Carl dth and I when we when we were both students we just started going through all the laws of physics
how would you control the brain well there's only so many kinds of energy there's mechanical force there's magnetism there's light you know the list is pretty short actually and so you can actually try to write down every possible way of doing it so I call this method the tying tree method where you
try to take the space of possibilities and break it down into parts so that the you know like so if you do if you draw it properly looks like a tree diagram here's the space of possibilities split into two parts and each of those splits into more parts and eventually covers a
page and looks like a tree and then the leaves of the tree the bottom nodes are ideas you could actually test by doing a literature search or doing an experiment and so a lot of our projects actually at some point or another involve this kind of can we think of every possible idea
approach and so we did not Pioneer this you know Fritz zi called this morphological analysis in the 1930s and he claims to have thought up dark matter and gravitational lensing and a lot of these Hot Topics that astrophysics that are being investigated today but of
course he thought these up almost a century ago he claimed to have thought up these ideas is through this sort of tiling tree or morphological analysis kind of approach for our final segment I have a few questions about what I call the Ed boen production function oh this
is about you how old were you when you started college well yeah so yeah around age eight or nine I got obsessed with this question of can we address the meaning of life through science and it may be very uh ambitious and hardworking and focused and so I started at college and
started working on this origins of Life project when I was only 14 I went to a program at the University of University of North Texas where they take people kind of young and so a lot of my classmates were 16 years old but um but yeah it was it was great to kind of jump directly into science you know I grew up
in a suburb of Dallas Texas which didn't have a lot of scientific stuff going on at the laboratory or research level so actually getting to jump into science was just transformative for me so more people should do this you think well it's a good question you know it's not
for everybody uh but but here's how I think about it but more right well here's how I think about so so I think a lot of us have sort of a skill phase of our career where we're learning how to program computers or we're learning how to you know machine metal or we're learning how to um do mathematics and
then at some point you want to go solve a problem right and I call that the impact phase you know some people go start a company or join a a research group or you know or whatever and so for me what I realized was that you know for me the the skills I wanted to learn and
the impact I wanted to do really required me to get my hands dirty get into a laboratory and start playing around with real matter but you know if somebody's more mathematically inclined or you you might not need to go into a laboratory right lots of great people do mathematics on their own now you've
trained in chemistry physics electrical engineering and Neuroscience correct well yeah so I started college at 14 and I started my my focus on chemistry for two years and then I transferred to MIT where then I switched into physics and electrical engineering and that's when I
worked on Quantum Computing and um and then yeah so five areas actually maybe more should more people do that well you know not the median student but more people so on the plus side I think I got a lot of very good groundings in fundamental sciences and that was very
important because now I can think about the brain in terms of physical principles or chemical tools or you know um engineering uh thoughts on the other hand it's kind of a slow process I was an undergrad you know for six years so I think the world's much faster paced nowadays than it was 25 years ago so and
also we have new hybrid in disciplinary Majors so one of the majors that I advise at MIT is biological engineering which is only like a decade old maybe a little bit more so you can now go to college and major in a discipline which will combine some computer programming and some chemistry and some physical
bottling and so forth so I feel like um you know again a theme of what I try to do as a professor is you know can we do on purpose what previously we did accidentally and so one thing I try to do is to help people craft curriculums that are optimized for what they want to
do and sometimes that means prescribing mixing and matching um that uh helps people sort of go in their own Direction so you you know when when word got out that I had two College dropouts in doing the PHD in my group a lot of other people started contacting me who also
had dropped out of high school or college say how can I get into brain technology and so I kind of designed a little custom curriculum for them where it's like you need to know some Physics but frankly you know gravity waves you don't need that if you're studying the brain and then you need to know some
chemistry but you know this kind of chemistry you know that might be not so important and so I and Mathematics too there's some parts of mathematics that are absolutely essential but other parts they're not you don't probably don't need that right away in inin science and
so I kind of designed a little custom curriculum like maybe in a in a year or two you can get up to speed by learning what's most important what kind of students are you likely to hire that your peers would not hire well I really try to get to know people at a deep level over a long period of time and
then to see how their unique background and interest might change the field for the better and so you know I have people in my group who are professional neurosurgeons and then as I mentioned I have college dropouts and I have people who we recently publish a paper where we
ran the brain expansion process in Reverse so take the baby diaper polymer add water to expand it and then you can basically laser print stuff inside of it and then collapse it down and you get a piece of nanotechnology and so the co- first author of that paper doesn't have
a scientific laboratory background he was a professional photographer before he joined my group but we started talking and it turns out if you're a professional photographer you know a lot of very practical chemistry and it turns out that our big demo and why the paper
got so much attention was we made Metal nanowires and the way we did it was using a chemistry not unlike what you do in photography which is a silfver chemistry so I really try to understand how individual people and their unique background and interest could change the world but it means that we don't have a
formula I try not to have formulas in general when it comes to the actual day-to-day of science you know I often say to people in my group you know we want to revolutionize the world for the better and do the right thing and be ethical but beyond that let's not try to
make any artificial policies other than waking up at 4:00 a.m. what is a person Al work habit you have that should be taken more seriously by others or that you would recommend to at least some people well I try to treat my own career as an experiment so I try to learn you know what am I good at what am
I not good at what do I like what do I not like and who tells you or how do you measure it what do you actually do well I experiment a lot on my own life I guess so for example this whole wake up early thing I arrived at by experimenting a little bit the way that I manag time I arrived at through lots
of experimentation so so for example I keep a calendar of future plans many people do but then I also keep a calendar of the past which logs how long it actually took for me to write that Grant or to meet with that person or to eat dinner or whatever and uh over time
I've learned a lot about how long it takes me to do something do you over or underestimate how long it takes you to do things well I started really keeping this calendar of the past not that long ago maybe 2014 is but in the last 5 years have gotten much better at estimating how long it takes me to do
something and it makes me a much better time manager uh for my future tasks two last questions first how do you use discoveries from the past more than other scientists do well one way to think of it is that if a if a scientific topic is really popular and everybody's
doing it then I don't need to be part of that right you know what's the benefit of being the 100 thth person working on something so I read a lot of old papers I read a lot of things that might be forgotten because I think that there's a lot of treasure hiding in plain site and
you know as we discussed earlier optogenetics and expansion roscopy both begin from paper from other fields some of which are quite old and which mostly had been ignored by other people so I sometimes Practice What I Call failure rebooting so we tried something or somebody else tried something and it
didn't work but you know what something happened that made the world different maybe somebody found a new Gene maybe computers are faster maybe you know some other Discovery from left field has changed how we think about things and you know what that old failed idea might
be ready for prime time so with optogenetics people were trying to control brain cells with light going back to 19 1971 and I was actually reading some earlier papers there were people playing around with controlling brain cells with like going back to the 1940s so what is different well this
class of molecules that uh we put into to neurons hadn't been discovered yet the same is true in economics I think like most of Behavioral economics you find in Adam Smith and pagu who are centuries old wow so I almost think you know search engines like Google often
are trying to look at the most popular things and I think to ADV science what we almost need is a search engine for the most important unpopular things sometimes I try doing searches I take the words I want and then I throw in a random word that is not related at all and I'll try Googling that or through
scholar. gooogle and I'll see what comes up absolutely I do that a lot too and that's one thing where I I really value those six years I spent learning a bit of chemistry and a bit of physics and a bit of electrical engineering because it allows me to stitch together some some
facts from different fields and that could be very helpful for launching a new idea or judging whether an idea is actually worth pursuing last question as as a researcher what could and would you do with more money well I'm always looking for new serendipitous things you
know connecting the dots between different fields and these ideas always seem a bit crazy and are hard to get funded and I see that both in my group but also in many other other groups so I think if if if I was given a pile of money right now what I would like to do
is to find a way both not just in our group but across many groups to try to find those unfund projects where number one if we think about the logic of it hey there's a non-zero chance it could be revolutionary number two um we can really in a finite amount of time test the idea and if it it works we
can dynamically allocate more money to it but if it doesn't work then we can deallocate money to it and if I think of optogenetics or expansion microscopy or these other techniques that we've been talking about the amount of money that we actually invested in it to get it
going was not that much they were actually fairly inexpensive projects and then finally I would like to go out and and treasure hunt you know let's look at the old literature let's look at people who might be on the fringes of science but they don't have the right connections or the right you know like
the people you know who I talked about earlier um they they're not quite in the right place to achieve the rapid scaleup of the project but by connecting the dots between people and topics you know what we could design an amazing project together Ed Boyen thank you very much
thank you it was great talking to you thanks for listening to conversations with Tyler you can subscribe to the podcast in iTunes Stitcher or your favorite podcast app and if you like this podcast please consider rating it on iTunes and leaving a review this helps other people find the [Music] show