Welcome to the Neural Implant podcast, where we talk with the people behind the current events and breakthroughs in brain implants in understandable way. Helping bring together various fields involved in neuro prosthetics. Here is your host, Ladan Jiracek. Hello everyone and welcome to the Neural Implant podcast. Today's guest is really, really cool actually. I had no idea, but in the end, turns out he is a really, really big pioneer in this field.
And we can thank him actually a lot for a lot of the breakthroughs in this field, a long time ago, two decades ago even. Now he is an adjunct associate professor and consultant. He is, he used to be, he's semi-retired, he used to be at the George and Tech. But now he's kind of just doing consulting work. But what he's so special is that he actually was one of the founders or one of the first people to build a two photon microscope. So being able to see proteins and protein reactions within cells
is kind of something that we can all thank him for. I mean, this is something that's very common nowadays. But yeah, 20 years ago, he did a lot of speeches and a lot of talks basically saying that this is possible. You can have really good resolution and be able to see what's what the brain is doing, what neurons are doing, how they're growing, how they're learning in effect. His main focus was cultured neurons, cultured cells.
And in this way, it's kind of a sandbox mode of being able to look at what neurons are doing and how a brain is reacting. So you don't have to go into a much, much more complicated rat brain, for example, but you could just go with this with less cells. Now, he also is a big advocate for learning and teaching open source, I guess, is what I'm trying to say. And I think this is amazing. Like this is this, this really struck a chord with me as you may hear in the episode,
because I'm all about this as well. This is why I'm doing the podcast. I want to share it with as many people as possible, share this knowledge, what I'm finding out, and just really these interesting people. And he's doing a lot of cool stuff with this. I'm going to be talking about it more at the end of the podcast. He has neuro writer and lots of other open source kind of projects.
And all of his papers are open source as well. So you can go on his website and find any of the papers that he's published and read it without being behind a paywall.
So I've really liked it. We talked about some really cool experiments, some really cool demonstrations, like backyard brains, where you can have these kits basically for a hundred few hundred dollars and be able to show basically children or anybody, the fundamentals of neurons and how it works and maybe even control other people's bodies with it. It's just really fun demonstrations. So I thought this was really cool.
And actually in the beginning, we were talking about how he's left the field and he's gone into consulting, how he left being a professor. And I was a little bit disappointed. I was like, oh, man, come on. You need to get back in so you can continue to grow the field. But he said basically, ah, it's too difficult or it was too big of a suck on my time. And I wasn't doing what I wanted to do. So this is where we start.
Anyways, guys, I really enjoyed this podcast. I think it was with the first of all, with the very groundbreaking person, leader in this field, truly a leader in this field. And it was very interesting as well, like nothing but interesting stuff. So hopefully you like it and we'll talk more on the other side. You're giving up this body of knowledge in your expertise. Couldn't you kind of have both, like have one as a hobby, something like that?
I'm decent at managing. You had a lab of about a dozen people at its biggest and, you know, we accomplished a lot. We published in fantastic papers. They're very well-sighted. We've made a lot of open source technology, both hardware and software. And we also shared a lot of our data. So I feel like we accomplished many things that are still out there. You know, they haven't gone away. These papers are still there. The data is still there.
And people are still benefiting from our neurowriter suite of software and hardware. But, you know, it was just too much of a slog for me to do all that and try to be a maker as well. Now, there were two summers in which I wasn't teaching and I was able to actually call in the lab and rebuild our two photon microscope. And those were the funnest times I had at Georgia Tech, where I got to spend full time in the lab, actually programming and doing electronics and optics and building a microscope.
Yeah, I mean, it sounds like being a group leader or, I don't know, somehow a manager, a glorified manager is not the position for you. But I think, yeah, like you said, there could be some kind of ideal position. And from the outside, looking like a programmer, a graduate student or something like this. But maybe that's the ideal for you and you could just come into that. I don't know, it's just, I think it's kind of a shame.
Like, I think you are good at this maker movement and I saw the Scrabble keyboard or I saw the wooden keyboard. But at the same time, I think it is kind of a shame to give up many decades of research and acquired knowledge. Because you have created stuff, but also I think the potential to create stuff is very big as well. Yeah, well, thank you for that. It was a tough decision. It certainly is a big part of my life. I still love it.
It's not like I'm leaving it because I don't like it or anything. I absolutely love the research we did. And I absolutely loved being a professor. But it wasn't really the managing aspect of it and sitting in my office writing wasn't the fun as part of it. And I would rather actually be making stuff with my own hands. Now, to say that I'm giving it up is probably not the right word to use because I'm still a consultant.
And if anybody wants to tap into my knowledge base, they are welcome to do that and to hire me and pay me money to do that. I don't review papers or grants for free anymore. I expect to get paid for it because I don't have a regular professor job. But I would like to continue to be part of this community and to interact with my fellow scientists and engineers. And to help to continue to push neuroengineering in the directions that we've set it going when we started this thing.
Interesting. So are you still up to date on everything and attending conferences and all this? I do attend some. I'm definitely not as up to date as I once was. It's very hard to keep track of all the different fields that I was dealing with, even when I was doing it full-time. Now that I've definitely moved into other areas that are unrelated, I spend a lot less time tracking the literature and going to conferences.
But I did go to the multilectro-terate conference in Germany about a year ago and gave a talk there. And I'm also keeping track on a lot of sort of new stuff to do with brain interfaces, mostly non-invasive interfaces like EEG and Transcranial brain stimulation. So that's kind of a new direction that my lab didn't actually pursue in a physical way, although we did talk about it and we think about it a lot. But we didn't actually do experiments with these kinds of non-invasive interfaces.
And I think the thing that I'm most excited about there is the potential for citizen neuroscience. You know that now laypeople can do experimentation that really was only once possible in ivory tower because the equipment is so expensive. Now people can afford to buy a pretty cheap EEG rig and do some serious neuroscience research in their makerspaces or in their homes or their basements or wherever in their schools. So citizen neuroscience could be a big thing now.
That's really impressive. What do the citizen neuroscientists need to know in order to get started in this? Yeah, well I suppose I'm a very, very much believer in learning by doing. And so the thing to do is to get either get some kind of a device that you can record your brain waves or go find somebody who has one and use theirs. A lot of makerspaces have these things nowadays and you could also volunteer to be a subject in some scientist research experiments.
You know if they often put out flyers to say please come and be a subject and will pay you $20 or whatever. So that's one thing you can do. But you can just go buy a, say the open BCI rig is only a couple hundred bucks I think and you could also get something like Mews. You know one of these EEG headbands that help you meditate and there are apps out there that allow you to hack into the raw data from the Mews. So you don't have to use their app.
You can use whatever app you want or write your own app. And just start playing around with the data and see what you can see and see what what effects you get by putting the electrodes in different parts of your head while you're doing things. You know the transcranial brain stimulation thing is also becoming kind of a hacker activity now that there are a lot of people that are building their own transcranial stimulators. It's a very cheap simple thing to build.
It's just a matter of you know regulating the current so that you don't electrocute yourself. You want to be able to deliberate about two milliamps maximum through your skull into your brain. And when people do this they're finding all sorts of interesting effects to enhance their learning or concentration or gaming abilities or depression is another thing they're helping fight depression.
So there are lots of things and we're kind of in the very early days of understanding how this works or even how best to implement it and I think that the citizen neuroscientists can really help out there by just trying lots of different things and seeing what works.
Yeah I was actually watching one of your talks and you were saying like there would be different settings you know for studying versus going to like social parties like I want level one for this and level four to be social and clever and stuff like this. Yeah well that was in regard to some implanted electrodes that had been implanted for the purpose of curing some fairly serious problem like Parkinson's or tremor or something like that.
So if you have electrodes already implanted and it turns out that they do something beneficial in addition to helping cure whatever disease they're trying to cure then why not take advantage of that you know why not tweak the parameters to optimize not only the curing of the disease but also the enhancing of whatever personality traits you want to enhance or ability to concentrate or reducing your depression. Yeah that's pretty impressive impressive. So how did you get into
this field actually? Well I guess that depends on what you mean by this field. I in grad school I did mostly biochemistry and I was in the psychobiology department at UC Irvine and I was working for Dan Oswald who was doing brain biochemistry because I had an undergrad degree from UC San Diego in biochemistry and he said wow you know it'd be nice to have somebody who knows
biochemistry in my lab. You know and the work that I did there I'm proud of it. We studied protein aging and this particular protein called cow modulin which is a very important protein in a lot of different cellular processes in the brain and other tissues but I really wanted to be a neuroscientist
and I really wanted to do some serious brain electrophysiology research and I didn't really get to do that until I was a postdoc and when I was thinking about where I wanted to be a postdoc I said what kind of a system when I like to work in and I thought it would be really cool to work in a system
where you can watch the learning happens study learning at a cellular and network way and some sort of a creature where you could actually see the learning process and I thought about maybe insects or worms or something but then I thought how about if you had neurons growing in a dish in a
petri dish maybe you can watch the learning process there and so I went to Caltech for my postdoc because Jerry Pine was there and he knew that some of the techniques that I knew I would want to learn to make this possible so at Caltech I spent eight years building the tools to study learning
in vitro which means that we founded this new field called embodied cultured networks where you take a network of brain cells that we usually got from rat cortex grow the menopetri dish and the petri dish is instrumented with electrodes on the substrate and you make a two-way interface
between the brain cells and a computer and then you can use that signals from the cells to control the robot or a simulated creature with an early control anemone so we built all these tools including the multilectro to raise and we built a Jerry Pine and I built a high-speed camera
for imaging neural activity and I was also working in the lab of Scott Fraser and in that lab I built a one of the world's first two photon microscopes for imaging living tissue and I want so this was part of the idea of watching the learning while it happens so if you if you
if you label tissue with some fluorescent proteins like green fluorescent protein you can see the neurons lit up under the microscope and if you use a two-photon microscope you can image them growing make time lapse movies without killing them and in 1996 when I built that microscope nobody
had done that before so so I was the first one to make a three-dimensional time lapse movie of neurons growing that were labeled with the green fluorescent protein and that was big dealbacked in you know even just to be able to image the green fluorescent protein in three dimensions was a
big deal and now it's kind of routine everybody in every biology department has a two-photon microscope and they're all imaging GFP watching neurons growing but back in 1996 nobody had done this before so it was very exciting and I basically gave a lot of talks saying look you
can do this too you could build a microscope it's not that hard to convert an old confocal microscope to two-photon and make it something that you can use to watch for example we image dendritic spines in collaboration with Aaron Schumann we were putting brain slices on the two-photon microscope
that were labeled with various different dyes and fluorescent proteins and we could watch the dendritic spines changing as we put on brain derived neurotrophic factor BDNF and this was kind of revolutionary at the time but now everybody just says oh yeah of course BDNF
changes your dendritic spines well we were the first ones to see that under the microscope watch those changes happen wow I mean I was learning about this in my master's so it's really cool I'm in awe to be you know talking to you the one of the pioneers of this this whole field
so what was your what was your goals of this I mean you you wanted to see how the the neurons were were growing and linking in order to understand it better something along these lines yeah to you know to watch learning happen it had been done a lot obviously a lot in animals in those
planning behavioral researchers out there and there were a lot of people I would say you know the majority of the hardcore neuroscientists were studying learning at a molecular level they were looking at LTP and they wanted to know which proteins were involved in long-term potentiation and
when the synapse changes its strength which proteins are involved in what gets phosphorylated and all the stuff there's a very molecular approach and they're doing mutations to you know fruit fly experiments and mutations to figure out what are the molecules involved but I thought there's
this huge gap in the middle there between the molecules and the animals that we really don't know much about we still don't know much about which is the networks level you know you can say okay I understand that a synapse gets stronger when you learn something but what does that mean
where is the actual learning happen is it at one synapse probably not it's it's it's it's it's it's at many synapses across a large network of cells and we didn't really have any tools to study things at the networks level in any great detail you know you could study them with functional MRI with
a voxel size of a few millimeters and one one cubic millimeter of brain tissue has hundreds of thousands of cells in it so so we're talking a gross analysis of the network level was possible but with something like two photon microscopes and microelectro you can study it at the single cell
level across networks and especially if you have it growing in a petri dish where you can look at every single cell in the network you've got them all right there under the microscope and if you connect them up to an anomat or a robot you can have a behaving animal that whose body is moved
away from its brain so that the brain holds still while it's learning this is not true for any animals you know animals tend to move while they're learning and it's hard it's very difficult to image their brains during the learning process because of that movement you know if you want to
look things at the microscopic level now that said there are a few fantastic experiments that have been done now with people who either fix the animal's heads in in a there's some kind of a vice that holds a very steady while they're running on say a styrofoam ball or they made a microscope
that's tiny enough for the animal to carry around on their head while they run around at a maze or something so there are other approaches that are of a similar goal as mine of watching the learning happen but at the time I started this those guys hadn't done that yet and I said well the only way
we could possibly see a learning happen is if the brain is holding perfectly still on the microscope stage and actually I mean even in those even in those cases I mean there is some kind of there is some vibrations from the body and blood pressure and everything like this you you get a
good amount of movement actually right and they've done a fantastic job of trying to reduce all those artifacts either with computational approaches or just sort of synchronizing them with the heartbeat or various clever tricks like that have now gotten to the level where they can see individual
spines changing while the animals are learning but but I think the in vitro approach still has merit it's still much easier than doing that in animals and I think probably the more importantly it's a much simpler system you know than a living an intact living animal is just an immensely
complicated beast even if it's an insect if we're talking about a hundred thousand neurons in a petri dish you have the advantage that they're mammalian neurons you know they really did come from a mammal so the brain cells are like the ones in humans however it's a much simpler network and
presumably might be a bit easier to understand what it's doing more than an intact animal you know that that raises the question is it doing anything relevant now that you've taken that out of the animal and I think by giving it a body you've given it some relevance you've given it a job to do
instead of just sitting there thinking it through itself it's now controlling a body it's getting sensory feedback from our closed loop system that we built and it's behaving and learning and changing and doing all sorts of interesting things now I was hoping that by building a learning a system
for studying learning that we might learn enough about how learning works to make people smarter you asked about my original goals and and that still is my original goal still is my goal to that neuroscience research might somehow shed light on the learning process well enough to make
us a little bit smarter a little bit more considerate and make the world a happier place that way this this hundred thousand neurons okay so I'm looking to step on Wikipedia right now so I'm not actually this smart but that's like a larval zebrafish or a lobster I don't know rat 200 million
so so yeah I mean like the the difference between a rat and and what you have in this is like I guess I guess taking apart like a a simple lawnmower engine and versus a you know very complicated I don't know diesel motor or something like this in a Mercedes so and but a hundred times more
or something like this so it's much much simpler to to look at and to kind of uncover what's really going on right yeah and also the fact that it's certainly mostly two-dimensional you know it's not quite a perfect monolayer but it's it's only about three-cells thick makes it a lot easier
to image into study into probe than a three-dimensional brain structure yeah you you had some pretty cool demonstrations with this actually you were able to have like a robot draw shapes and everything like this from from this this brain and even to have it centered over the internet so so it was
disembodied so to say yeah we had you know it was like art science collaboration that we did with the guy Benari and Phil Gambling and symbiotica in in Perk Australia they built the robot the drew pictures on big sheets of paper and they said do you think we could control it with our
with our culture dishes and I said yeah I think I definitely think we could do that and we did that we built system this was 2002 the project was called Mayart and then another version of it that they built was called silent barrage and this thing was immensely successful going around
to different art galleries all over the world where we had the brain sitting in our lab controlling robots somewhere far far away and in some sense the internet was part of its nervous system and two-way communication going back and forth so for example in the silent barrage exhibit
when people walked through the exhibit video cameras recorded their position and that was used to stimulate the neurons in the dish in our lab and then the neurons would respond and those responses would get sent to the robots to control their movements that's really cool so what were
some of the challenges in this research of the the cultured neurons well certainly just keeping cultured neurons is a lie keeping them alive is a big challenge they must be kept sterile because they when as soon as you take them out of the brain they no longer have an immune system so if a
single germ gets in there they're dead and we developed a system for keeping them alive longer than anyone else had done for neural cultures I think our oldest culture lived to be two years old and my post doc Tom DeMars was the one who took care of them for those two years and he
he did lots of experiments on one culture that we called the Methuselic culture because it had lived so long and this the idea was not very complicated I just built these lids for the culture dishes that were porous that allowed gases to go through the Teflon membrane and that would keep
the cells happy but it also kept the germs out and it also reduced evaporation sometimes when the culture medium evaporates the cells get very unhappy so it was kind of a way to just maintain the environment of the cells in a happy environment and this method for keeping cultured neurons alive
for a long time has now used all over the place in that paper which we published that technique is I think probably our most cited paper so so that was one of the big challenges with just you know long-term survival of these cultures so that we could do some long experiments with them
another one was making the closed loop system so we wanted to be able to take signals that we recorded from the brain cells in the dish and to process them very quickly and use the results to stimulate the cultures so you could think of this in the embodied system as a sensory
motor feedback loop so the recordings that we're getting out of the dish are used to move the robot around or the simulated animal they they are the motor commands they're moving this thing around and then that the anomat or the robot has a sensory system some kind of sensors like
like ultrasonic rangefinders or wheel encoders and those sensory devices get translated by our electronics into electrical stimuli that we delivered back to the culture dish so to build this closed loop system that's fast enough and we're talking about 10 milliseconds to go around
the loop here it took quite a bit of technology and engineering to do that and that was done in first by Tom DeMarce and then by my graduate students Daniel Valkenar they built these fantastic multi-electro stimulators that are being used by lots of other people because we made it all
open source and shared the plans for these things another another way that you're a pioneer this is really this is really amazing that this field has to you know might even be named after you slowly well I don't really care as much about that is that more people use it you know I wish that
it didn't really catch on in America for some reason I think mostly because the funding agency is very skeptical that you know they're not they're pretty conservative the NIH especially is very conservative in terms of the kinds of neuroscience that they would like to fun and it was the
Italians that really picked up on this there's some very good Italian research that uses these nearly controlled animates or embodied cultured systems on thinking of Michaela Chapaloni and Sarah Giro Martinoia especially and then also a few Japanese groups Suburukudo is one that's
doing this and you know a few scattered ones Shimon Narrow and Israel is also picked up on this and done some fantastic work so a few groups had said you know yeah the in vitro closed loop systems could be a useful mechanism for studying all sorts of neuro dynamics where you have a tractable
system of simple enough that you could conceivably look at the whole network and map it out or even make it well-defined Bruce Wheeler is one of the few people in America that really has been pushing this for some time to to create a network of a certain architecture in vitro so that
might carry out certain types of computations or something and by making all of our tools open source and all of our code available and also by sharing a lot of our data we put we posted a lot of our data online for other people to look at and to analyze we're encouraging people to pick up
on this idea and to try it out themselves that's that's amazing that's actually I guess that's the future of research and and this kind of frictionalist collaboration not having to wait for a scientific paper to come out which is you know as you know a many-month-long process
and and have them being able to pick up on it within days yeah a lot of times you know you they put even if you're trying to publish something the actually force you put an embargo on thing so so that if you have released it certain journals will say no we won't publish that you know
we only want to publish something that is brand new that nobody's ever heard of before and so we just avoided those journals we mostly published in open journals where you can download the papers freely and if they're not open journals we put the papers up on our website since 1995 you know
I I created the website for the Pine Lab when I was a postdoc there and put all of our papers up there since 1995 for free downloading that's been an annoying thing for me you know especially having been in academia having done done my masters and then now out of it I I'm like oh man
I really didn't I guess take advantage of it enough like this free access to research papers and so I'm really grateful to you actually before before this call I downloaded a good amount from yours and and also there's there's one frontiers of science you know previous guests for
Mikhail Lebedev and he's like yeah all 160 papers on there are for free so I was like thank you finally I can start reading something and and actually learning more than than I used to so it's really it's really aggravating it's I think it has to end this this paywalls yeah it is changing and
there are you know for example any research that's funded by the National Institutes of Health in America has to be open they they have a rule there that once you publish a paper you have to make it freely available and so they kind of got around the publishers pay walls by saying well what
we'll do is we'll create our own HTML version of your paper and that HTML version is the one that people can download freely so it's maybe not the exact same as the paper that that you publish but it contains pretty much all the same information maybe in a different formatting
and I really appreciate the fact that NIH made a rule like that definitely yes so I really like these this idea of the culture neuro and I think it's I think it's really really cool like kind of a sandbox in which to play with and learn a little bit more about the brain what do you think the future
breakters will be in this field well as I mentioned the funding you know was always an issue especially in America and some exciting things are happening it seems to me that some big organizations outside
of academia are taking this on as a challenge the whole neural interfacing idea and I'm especially excited about neural ink you know mostly because I just am such an admirer of Elon Musk every single thing that he tries to do he seems to succeed way beyond everybody's expectations you know he got
behind electric cars they're now the way best electric car on the planet by far he got behind solar power he's pretty soon going to be putting solar tiles on everybody's roofs he got behind rockets and they're the best cheapest rockets that you can use to get to the space station right now
so if he puts his money and his energy behind neural ink this company that's going to do neural interfaces I'm I'm assuming and hoping that it will accelerate the same way his rockets are you know that this thing is just going to take off and it'll just be way better than the kind of
academic research where we're just making progress by tiny little increments every time we get one small grant we can do a little bit more progress if you have a big expensive big rich company with lots of wheelbase then maybe the neural interfacing field will really take off and I'm hoping that he
and others will start to appreciate that you sort of need the sandbox approach you know you need some simpler system to to start with if you're going to do neural interfacing a lot of the interface research that we did is applicable to living systems so for example the last thing that we did
research on before I closed my lab at Georgia Tech was to do a closed loop optogenetic system so half of the loop was optical with fiber optics going either into cultured dishes or into living rats and and we used that to to stimulate the neurons either to make them fire more or to reduce
their firing and then we used electrodes to record the neurons and we made a fast closed loop to study sort of slow learning called homeostatic plasticity and this this is a really useful system that could help with certain kind of kinds of diseases like chronic pain epilepsy, tinnitus all of these
things are problems in homeostatic plasticity and you could say oh let's study this in animals or let's study it in people but to study it in vitro first is is a very good first step because you have so much more control over all the variables so we built this closed loop optogenetic system it's
called neural writer and John Newman was the graduate student of mine who did most of the work designing and building that John Ralston before him made the first version of neural writer and neural writer is freely available anyone can download the software and the plans for the electronics and solder it together themselves and start doing their own closed loop research if they want to for pretty cheap you know we're talking about $5,000 compared to a commercial rig that you
might buy which is probably $100,000 so we're trying to open it up to more researchers that don't have so much resources but if a big company like neural ink wants to take it on they can just get get right into it because of the available systems that we put out there like neural writer
what would be would be the the thing that's stopping it for getting getting another 10x drop in price so down from $5,000 to maybe $500 or $50 yeah I think there really isn't anything stopping it so an example that that's already happening is backyard brains you can buy for $100 you can buy
rig for recording neural signals from cockroaches or from your own body using they have a thing called the human control human experiment where you you hook up electrodes to your arm and your muscle signals get recorded amplified and used to stimulate another person's muscles and make
their arm move and this is fantastic any hacker or even just a hobbyist can do this with $100 backyard brains kit so there's no there's no wait there's no reason why we can't do this very cheaply now and our the system that we designed for this op of genetics that probably the limiting
factor there is the genetic constructs are fairly difficult to make but they're being distributed freely by Carl Dicer-Off and Ed Boydon these guys who really got opted to put op of genetics on the map have been very good at sharing all the constructs that they built and you you get a little
test tube with some viruses in it and the viruses infect the neurons and make them light sensitive and then you just get out your fiber optics and start experimenting with them so it's it's fairly cheap to do it's just technically there's a lot of technical difficulties you know taking care
of the neurons and getting all this fiber optics and LED stuff working properly hopefully not just our rig but other people will will make devices that are more reliable and easier to use and more plug and play rather than for you know serious experimentalists who are good at electronics
to do wow this is really cool I'm looking at this backyard brains this is going to be this is amazing I think this would be great for demonstrations and and teaching kids how to do this as well well this is really cool like especially if you can get a lot more brains behind it and get a lot
more I don't know interested people and have it be easy like have the barrier to enter be be lower I think that's when you really get a revolution I think that's when computers and software for example really exploded when when you didn't have to go to the university mainframe but you
could actually like program at home and get your own stuff done and now with apps and everything like this you could it's just to click away it's a fantastic analogy I think you are you really put your finger on where we're at now with this citizen neuroscience we are exactly right at the
point where the personal computer came on to the scene and I was I was there I wasn't much of a hacker but I was I was right there in the computer lab in high school with my friend who had an apple to e one of the first apple to e computers and and we were sitting there making computer games
on it you know and he was he was the one who knew how to program and I was kind of coming up with the ideas for what he would what he would program and we made a great team doing that and it was incredibly empowering as you say that we suddenly you know instead of having to deal with some
big mainframe computer we could just do this in our own spare time and in his house packing way there so this is now something that people can do with brain cells they can go out collect a cockroach or they're a worm or whatever their favorite creature they want to study or
study their own muscle signals or their own EEG signals and start to do some interesting experiments this is really cool yeah I mean I want to do lots of lots of teaching I guess you know to to children you know basically 10 year olds I think if you can't explain this stuff to a 10 year old
then you don't understand it yourself and I think this is this is the greatest way to do it this is really cool I'm really excited this is this is why I do the podcast I'm glad that I'm glad you used to share my enthusiasm I one of the things that I did when when I was on my maker sabbatical
we toured all around Ireland and visited all the makerspaces and one of them called former labs in Quark City it's a bio makerspace and I gave a demonstration there where I brought my backyard brains stuff and hooked people up and showed them their brain waves and their
heart signals and muscle signals and and I basically couldn't get them to go away you know this is supposed to be a 45 minute presentation workshop thing and it was standing room only in former labs and the people just kept saying try that try that you know and after an hour and a half I was
exhausted and they all they I said you know I think I think we've done enough demonstration to do we should call it a dog so there's obviously a desire out there especially in kids to do this kind of stuff you know it's very exciting and if they hear that it helps them do their gaming you know
if it makes them better gamers they get very excited about it so so I don't think it's hard for kids to understand the excitement of it and to explain to them what's going on in the nervous system I hate to say it but even to my college students we don't understand you know and I'm explaining it
to college students there's so much about the brain that we don't understand in the nervous system that we pretty much just have to say look what rudimentary understanding we have now is enough to do some pretty cool things and we can solve certain diseases and we can improve certain conditions and
we can perhaps enhance the brain with our rudimentary understanding imagine how much further we could go if we understood even more wow yeah definitely and power them you know basically give the ability to 15 year old of what a professor could do even five years ago some playing this
yeah definitely citizen neuroscience I love it I love it this is probably my my takeaway from this and yeah this is this is really interesting so I'm kind of I'm kind of curious what do you think is maybe wrong with this field like like what is a big mistake or wrong direction that some
researchers may be going down in this field you know I don't want to disrespect people doing this research because I think some some really good research has been done patterning neurons on culture dishes figuring out what kind of substrate cells like to stick to or don't like to stick to
but I feel like it's too early for us to design a specific architecture in a dish that we don't really understand enough about how the structure of a network affects its function to say here's a structure that we should choose so our approach in my lab was always to let the cells randomly
connect the way they want to connect we never did try to impose any specific architecture on them you know that's that's what really a minor complaint I as I say some important research has been done to try to make the fine networks and usually when you do that you find that it's really
really hard the networks will connect the way they want to connect not them but you want them to connect and that's there's an important lesson right there so you know I suppose the other main thing which is a soapbox that I've gotten on many many times is that closing the loop is
really important if you just poke an electrode into a neuron and record from it you are only getting half of the story there you know and there are a lot of neuroscientists who do that who only either stimulate the only just stand sensory input into some animal and they look at their
neural signals or they look at some motor output and they don't let the animal do this full loop where it's receiving sensory input but making a decision and then acting on it by behaving in a certain way so I really think it's important to get some kind of a closed loop system and to do
this in vitro is technically difficult but we did it we made the tools they're now available to anyone who wants to do this and make a closed loop system where you can have not only inputs but outputs interacting with each other and I think when you do that you'll have a much more natural
neural circuit instead of this you know sort of I guess the way I think of it is a lot of culture dishes with brain cells in them are in sensory deprivation they're just sitting in the incubator not getting any inputs and if you think about an animal or a person in sensory deprivation their brain
is not working properly it goes crazy pretty quickly and you start to hallucinate and all sorts of strange things happen because the nervous system evolved to get sensory input you know it's always expecting sensory input and if you don't have that you have an aberrant strange misfunctioning
nervous system dysfunctional nervous system so so I think it's really really important if anybody wants to study the nervous system whether an animal is a vitro or a people that they make it a closed loop study where you have you have sensory input and behavioral output all in the system there
with the cultured cells with a cultured neurons how do you change the structures of the neurons do you do with proteins or do you do with the actual geometry of the electrodes that that is like the base of the the petri dish yeah so I talked about a couple of different kinds of structural changes
I suppose most recently I was referring to people who were trying to impose a certain structure on the network and that's not very easy but the most common way of doing that is to make a surface that the cells will stick to in a certain shape so you pattern a certain kind of molecules
that are adhesive to the cells like for example polyethylene amine is one that we used in this and you could pattern that using masks and in the kinds of techniques that they used to make microchips and create a substrate that where the neck where the cells that land on that's
such great we'll stick to it and if they land somewhere else they won't stick and they'll die off or they'll move over to where it's sticky so that's one kind of structure that I was talking about I was also talking about the kind of structural changes that we observed during the learning
process which are the ones that the neurons do themselves you know if you watch any of these time lapse movies of neurons growing they are incredibly dynamic creatures if you watch them under the microscope with your bare eyes they're moving kind of slowly like the mid-hand on a clock so
you don't notice a whole lot but if you speed it up about a factor 10 their movements are very dynamic and they're constantly reaching out and forming new connections and breaking connections and they're doing that with you know the the neuron has a sort of a muscular system inside of it which
is based on the protein called actin and actin is one of the proteins it's in all muscles but believe it or not all the dendrites and axons of a neuron and all of its dendritic splines have these actin protein and other proteins that interact with the actin filaments to move
this pieces of the neuron and allow them to reach out and grab onto each other and form new synapses and get branchier and become much longer you know they can axons can follow a sense trail they're smelling their way along until they make a connection to the right target neuron or
muscle cell or some other structure in your brain or in the rest of your body perhaps so there's structural changes are just an inherent part of the life of neurons they don't hold still for very long they're constantly changing their own structure I guess it would be difficult to change
the change the structure of it in such a system and I assume to recall that at the actin filaments also depend on the stiffness of the neighboring materials as well and depending on the stiffness of the neighboring material they they change and they I don't know they I guess determine
what the cell will do as well oh yeah very much so the the physical substrate that they're growing on not just you know I was talking before about the chemical nature of the substrate they're growing on determining what shape they are and whether they adhere or not but but just
the physical nature of it determines how they grow and I suspect that's because the neurons tend to follow certain structures in the brain to get to their targets and for example during development an embryonic development of the brain there are these glial cells that go from the middle of the
brain out to the surface called radial glia and the neurons just use them as guideposts they they they grab onto the radial glia and they just follow them up to the where they need to go in the cortex so it's a physical structure that they follow and if you grow them in a dish with
lots of grooves cutting it they will tend to follow the grooves and so some researchers just pattern neurons just by solely by physical structure and the neurons are very sensitive to these small features on the order of a few micron size their little growth cones as they're growing along are sensing these structures and this making little decisions about where to grow and where to
connect based on the structure of the environment they happen to find themselves in. It's maybe like a a great vine following twine or something like this yeah exactly that's exactly right the radial glia are just like the twines in a garden. So do you have any recommendations on who we should talk to or what we should read you already mentioned some names but maybe some other people
that that you find interesting. Well certainly you know since your focus on neural implants some of the pioneers of neural implant research maybe you've already interviewed these folks but for example Dick Norman who invented the Utah array is one of my heroes you know it's really
made some fantastic research there Ken Wise is the Michigan probe guy John Donahue and Andy Schwarz have done some fantastic work in monkeys and in people so but if you're talking about in vitro research my post documentor Jerry Pine is still alive and kicking I met him about a year ago and
and although he's getting pretty old he's still fully with it and would be worth talking to about the history of multi electrode arrays and cultured issues with neurons growing in them because he's he really got that going in the 70s there's another guy named good to grows who did it simultaneously
independently of him will be worth talking to he was at University of North Texas in Denton let's see who else oh so I was going to say that there are people that are kind of on the cutting edge of this neural implant research at the Allen Brain Institute have you talked to any of them?
No I don't think so yeah so definitely look up I'm not sure who exactly it is there that's doing that these days but but the Allen Brain Institute really has mates and fantastic accomplishments and they're always sharing everything they do with the public so I just love their philosophy
and their goal is to sort of understand the higher brain functions like consciousness by studying model systems like mice you know and put them in very well controlled environments and with lots of electrodes poking into their heads and microscopes watching their brain stuff so definitely
check out the Allen Brain Institute you know in terms of the philosophical mentors that I like to read and to think about Kevin Kelly is my favorite right now have you have you read this book and the inevitable that's a new one no I don't think I have yeah so the inevitable is where he's
proposing pretty much what's going to happen in the next 50 years or so with with everything you know he really covers everything he does talk a lot about artificial intelligence and he talks a little bit about the brain interface stuff that's not not his focus he's he's much more about
computers and the internet and what's the future of society given the technology is changing so fast and Kevin Kelly he was the editor-wired magazine and he's written some fantastic books before this so he's really got a lot of credibility when he makes a prediction it usually comes true so
you know he's not a white he's not a crank he's not somebody who's just guessing he really has a lot of facts to base everything that he says and I think the inevitable is is just an enjoyable read for anybody who cares about the future of technology he's got one before that that's called
what technology wants which kind of treats technology as a life form and and if it is a life form well where is it going and does it care about humans you know what are we part of its master plan so so there's some interesting philosophy to think about there that he's got gotten me and other
people thinking about by writing these books yeah I've read that one what technology wants and I I would also highly recommend it like basically saying that technologies its own thing almost like an ant colony or something like this or like a termite house and it's really just using us to
build itself something like this so Kevin Kelly is my favorite thinker right now and anybody who listens to your podcast will probably find his writing accessible and interesting many listeners are just starting out in this field so what recommendations do you have for them to get
into the field of either cultured neurons or neural implants or brain machine interfaces yeah so that's a very good question um I say you know to anybody who expresses even a little bit of interest in this obviously the first thing is to go read scientific papers about it and as I
mentioned all of our papers are freely downloadable from our website if you go to potterlab.gattek.edu and to the publications page you can read all our papers you can get to most papers by searching for things on Google Scholar probably some version of it that you can download usually but but I
think you know I as I mentioned before I'm a big believer in learning by doing and if you have a chance to get into a lab and actually do some research you should do that it doesn't matter if you're a high school student or a college student or even somebody who's who's you know already
past college age you want to just be a nontraditional researcher of some sort volunteer to work in somebody's research lab and spend some time there getting your hands dirty growing neurons and collecting data from them and trying to crunch the data and figure out what the hell it means
I think you will learn so much more and more quickly than by studying a lot of books and reading a lot of papers obviously doing what you're doing talking to people who are already in the field is a very good way to learn this thing you know so just fine you know start by reading the papers
and say oh this person has written several interesting papers and ask those people questions based on their papers and I guarantee you any scientist or researcher who gets a question about their papers will answer it doesn't matter who you are oh no I'm going through this audio right now
and it turns out that the last I don't know 10 minutes or something like this of Steve Potter's audio was cut off so no but anyways based on my questions because my my audio was still there we talked about how you should just kind of push yourself into an internship and push yourself
into a lab for minimum of a few months because that's when you become the most useful and then finally if you don't know something you should remedy that with reading lots of journals read read read and I talk about a story or my experience with this of how I was kind of bad in my master's thesis
but that it was only when I started reading and read like 40 50 papers that I started to figure out what the field was like and yeah was able to be helpful again so don't worry if you're not helpful for the first few months you will be eventually and this is how you're going to get into the field
anyways guys again sorry about this but technology what can you do what can you do there's something weird I remember there was something weird about the recording and yeah hopefully you enjoy this and and you can reach out to Steve Potter on his website or LinkedIn or just generally
the same ways you would find any guests on this show just type Steve Potter neuro into Google and BingBang Boom you got it so hopefully you guys enjoyed it yeah it was really interesting like I I think it's kind of a shame that he's gone down this road of of basically not being a professor
not being so heavily involved in the field anymore and I think he's a very smart guy he's a builder he's a creator you know so it needs to continue I think but but he wasn't very happy so it's it's just kind of a shame that that he's not able to be helping out in this field as he used to be
so hopefully like me you enjoyed this episode and found it very informative again you know when we got on to this field or this topic of basically open source and teaching children and all this kind of stuff I really resonated with this I really enjoyed this is this is absolutely the future and
being able to explain these things simply is very very important that's that's the point that's the goal of this podcast let me know if I'm actually doing it so hopefully enjoy this I really like this interview I think this is what the interviews should be like this is a little bit philosophical
side you know keeping stuff open source but also talking about the nuts and bolts of this so hopefully you've enjoyed this please let me know what you think about this please write to me neural implant podcasts at gmail.com I love getting your guys's response your feedback and honestly I can make
the show better and if you give me feedback as well of who I should have on the show that's that's another great thing but I just love just generally getting feedback from you and and learning about you as well and we can start a conversation I really like this I really appreciate it and it's
it's starting finally you know it's it's finally I'm getting I'm getting more and more feedback so it's it's great this this show is here to stay this show was launched just a few months ago but I love it and I'm learning so much and the feedback from you is great so I'm going to continue because
I'm learning as much as you are so until next week this is the neural implant podcast hope you enjoyed the show we're able to learn something new bringing together different fields and novel ways until next time on the neural implant podcast