WEBVTT - Ep90 "What's the future of connecting our tech to our brains?" 0:00:05.120 --> 0:00:09.039 Why is it so hard to reverse engineer the brain? 0:00:09.240 --> 0:00:11.480 Can't we just measure the signals and all of the 0:00:11.520 --> 0:00:15.040 brain cells and then figure out the neural code. And 0:00:15.080 --> 0:00:18.040 if not, why not? And what does this have to 0:00:18.079 --> 0:00:23.160 do with solving vision loss and eavesdropping on the activity 0:00:23.160 --> 0:00:29.319 of cells using other cells and communication between brains using 0:00:29.360 --> 0:00:35.479 something other than conversation or observing and understanding and maybe 0:00:35.600 --> 0:00:43.000 changing our own experience of the world. Welcome to Intercosmos 0:00:43.080 --> 0:00:46.239 with me David Eagleman. I'm a neuroscientist and author at 0:00:46.240 --> 0:00:49.800 Stanford and in these episodes, we sail deeply into our 0:00:49.880 --> 0:00:55.720 three pounds universe to understand the mysterious creatures inside the 0:00:55.760 --> 0:01:00.160 eighty six billion neurons that are chattering along with tiny 0:01:00.440 --> 0:01:08.479 electrical and chemical signals producing our experience. Now, today's question 0:01:08.640 --> 0:01:12.480 is how do you actually get inside the brain to 0:01:12.560 --> 0:01:16.160 study it? After all, we know that the brain is 0:01:16.280 --> 0:01:19.480 the root of all of our thoughts and hopes and 0:01:19.640 --> 0:01:23.679 dreams and aspirations and our consciousness. And the reason we 0:01:23.800 --> 0:01:28.080 know this is because even very small bits of damage 0:01:28.080 --> 0:01:31.880 to the brain change who you are and how you 0:01:32.000 --> 0:01:36.039 think and whether you're conscious. Note that other parts of 0:01:36.080 --> 0:01:40.320 your body, like your heart, can get completely replaced by 0:01:40.400 --> 0:01:43.839 a machine and you are no different. Or you can 0:01:44.280 --> 0:01:47.000 lose your arms and your legs and you can still 0:01:47.040 --> 0:01:50.560 be conscious, or you can get a kidney replacement and 0:01:50.800 --> 0:01:53.200 you're still thinking about your life and your family and 0:01:53.200 --> 0:01:56.800 what you need to do tomorrow. But even a tiny 0:01:56.880 --> 0:02:00.800 bit of damage to the brain caused by let's say 0:02:00.800 --> 0:02:03.800 a stroke or a tumor or a traumatic brain injury, 0:02:03.840 --> 0:02:08.480 even a small bit of damage can change you entirely. 0:02:09.000 --> 0:02:11.440 Even if you don't lose your consciousness, you might lose 0:02:11.480 --> 0:02:16.000 your ability to think clearly, or to speak, or to move, 0:02:16.760 --> 0:02:21.280 or to recognize animals or understand music, or understand the 0:02:21.320 --> 0:02:24.520 concept of a mirror, or a thousand other things that 0:02:24.560 --> 0:02:29.040 have taught us over the centuries about the complex landscape 0:02:29.440 --> 0:02:33.240 of this three pound inner cosmos. So we know the 0:02:33.240 --> 0:02:37.240 brain is necessary for our cognition and experience, but we 0:02:37.360 --> 0:02:41.720 didn't get to that understanding through detailed studies of the 0:02:41.760 --> 0:02:47.279 intricate circuitry, but instead mostly through observations of crude damage. 0:02:47.720 --> 0:02:52.160 So there's still an enormous amount that we don't understand 0:02:52.240 --> 0:02:55.800 about how the whole system works. We only have a 0:02:55.840 --> 0:02:58.880 sense of how it breaks. It would be like if 0:02:58.919 --> 0:03:02.160 you were a space salien and you looked at cell 0:03:02.240 --> 0:03:05.200 phones and discovered that if you zap the phone with 0:03:05.280 --> 0:03:09.760 your laser, then it doesn't make calls anymore. Okay, that's important, 0:03:09.760 --> 0:03:14.120 but it doesn't tell you how telecommunication works in terms 0:03:14.200 --> 0:03:17.960 of base stations and frequency bands and compression and sim 0:03:18.000 --> 0:03:21.400 cards and everything else. For that, you would need to 0:03:21.480 --> 0:03:24.640 take off the cover of the cell phone to figure 0:03:24.680 --> 0:03:29.640 out what the billions of transistors are actually doing. And 0:03:29.680 --> 0:03:34.480 that's really our modern challenge in neuroscience to study this 0:03:34.639 --> 0:03:41.840 incredibly detailed system more directly. So why is progress still 0:03:42.160 --> 0:03:45.680 so slow on that front? Well, it turns out it's 0:03:45.760 --> 0:03:51.320 very hard to study the brain's trillions of neurons directly, 0:03:51.760 --> 0:03:57.520 this pink, magical computational material that mother nature has refined 0:03:57.640 --> 0:04:02.920 through hundreds of millions of years evolution. Why because this 0:04:02.960 --> 0:04:06.640 is the computational core, and so mother nature has protected 0:04:06.640 --> 0:04:10.320 it in armored bunker plating. So that's the first challenge. 0:04:10.360 --> 0:04:15.160 The brain is tightly protected inside the prison of our skull. 0:04:15.920 --> 0:04:17.680 But that's only part of the challenge, and that can 0:04:17.720 --> 0:04:22.520 be addressed by careful neurosurgery. The bigger difficulty is that 0:04:22.720 --> 0:04:25.520 even when we can get in there by drilling a 0:04:25.520 --> 0:04:28.560 little hole in the skull. What we find is an 0:04:28.560 --> 0:04:35.080 incredibly densely packed device made of very sophisticated units that 0:04:35.160 --> 0:04:39.799 are microscopically small, and there are almost one hundred billion 0:04:39.880 --> 0:04:43.040 of them, which is about twelve times more than there 0:04:43.080 --> 0:04:46.920 are people on the planet. And each one of these 0:04:47.000 --> 0:04:52.640 neurons is sending very tiny electrical signals tens or hundreds 0:04:52.680 --> 0:04:56.600 of times per second, and these signals zoomed down axons 0:04:56.920 --> 0:05:02.000 and cause chemicals neurotransmitters to be released. And it's not 0:05:02.400 --> 0:05:07.760 generally clear how to read this insanely dense circuitry to 0:05:07.880 --> 0:05:13.960 understand how these trillions of incredibly small signals racing around 0:05:13.960 --> 0:05:18.040 in there lead to a particular outcome at the scale 0:05:18.240 --> 0:05:21.880 of a human like you move your arm, or you 0:05:21.960 --> 0:05:26.200 have a craving for pistachios, or suddenly you're reminded of 0:05:26.240 --> 0:05:31.080 the poem osomandias or whatever. What is the relationship between 0:05:31.400 --> 0:05:34.839 this small scale and the large scale? So how do 0:05:34.960 --> 0:05:40.080 neuroscientists try to decode this incredible complexity. The answer is 0:05:40.640 --> 0:05:45.240 by marrying the technology that we have like computers, directly 0:05:45.320 --> 0:05:48.200 to the cells of the brain. And this is what 0:05:48.240 --> 0:05:53.479 we generally call a brain computer interface or BCEI. We 0:05:53.640 --> 0:05:56.799 use that term to refer to essentially anything that allows 0:05:56.920 --> 0:06:01.200 direct communication between the brain and to an external device. 0:06:01.240 --> 0:06:05.960 So people use these to control wheelchairs or robotic arms, 0:06:06.360 --> 0:06:09.600 or type directly onto a screen or speak through a 0:06:09.640 --> 0:06:14.360 synthetic voice. The idea is to use BCIs to restore 0:06:14.520 --> 0:06:19.160 functions in people who have lost them, like paralysis or blindness, 0:06:19.360 --> 0:06:24.159 and someday perhaps to enhance the capabilities of healthy people. Now, 0:06:24.360 --> 0:06:28.680 how does a BCI actually work. People sometimes think about 0:06:28.760 --> 0:06:32.360 BCIs as measuring electrical activity on the scalp with an 0:06:32.400 --> 0:06:36.320 EEG electroncephalogram, and that counts, but you don't get very 0:06:36.400 --> 0:06:39.359 much detail from the outside of the skull. So the 0:06:39.440 --> 0:06:45.599 more sophisticated forms of BCIs involves measuring brain activity directly 0:06:45.800 --> 0:06:48.720 from the cells. And the main way to do this 0:06:49.120 --> 0:06:52.800 is with small metal electrodes that you insert into the 0:06:52.839 --> 0:06:57.000 brain tissue. And with these electrodes you can send little 0:06:57.200 --> 0:07:00.160 electrical zapps to stimulate the neurons, and you can can 0:07:00.200 --> 0:07:04.599 also listen to hear when the neurons themselves are giving 0:07:04.640 --> 0:07:08.480 off small electrical signals. Now, this has been a technology 0:07:08.480 --> 0:07:12.600 that researchers and neurosurgeons have used for many decades, but 0:07:12.760 --> 0:07:15.320 it's still a challenge because you have to drill a 0:07:15.320 --> 0:07:18.480 hole in the skull and these little, tiny metal electrodes. 0:07:18.520 --> 0:07:21.640 Although they're tiny, they're actually pretty big from the point 0:07:21.640 --> 0:07:24.120 of view of neurons. From the point of view of 0:07:24.160 --> 0:07:27.440 the neurons, it's like inserting a tree trunk. It damages 0:07:27.520 --> 0:07:31.320 the tissue. Now you've probably heard of companies like Neurlink. 0:07:32.000 --> 0:07:36.040 They're still inserting electrodes just like neurosurgeons have done for decades, 0:07:36.240 --> 0:07:39.480 but they're working to make them smaller and finer and 0:07:39.640 --> 0:07:43.960 robotically inserted, and also wireless in their communications so the 0:07:44.000 --> 0:07:47.520 information can go back and forth without having a cable there. 0:07:47.720 --> 0:07:51.120 So it's a better version of the same idea of 0:07:51.160 --> 0:07:55.600 sticking electronics into the brain. But are there new ideas 0:07:55.680 --> 0:07:58.840 about how to read and write to brain cells, about 0:07:58.880 --> 0:08:01.560 how to interface with the brain. Today, we're going to 0:08:01.640 --> 0:08:04.240 talk about what is at the cutting edge, and so 0:08:04.440 --> 0:08:07.160 for that I called a colleague of mine who is 0:08:07.520 --> 0:08:12.440 shaping the future of BCI technology, Max Hodak. Max is 0:08:12.600 --> 0:08:17.720 an unusually brave thinker. He started studying brain machine interfaces 0:08:18.080 --> 0:08:21.120 as an undergraduate, and while most people would be thrilled 0:08:21.120 --> 0:08:23.840 to simply be a part of that. He was already 0:08:23.880 --> 0:08:26.840 thinking about the ways that parts of the science were 0:08:27.200 --> 0:08:30.400 inefficient and could be improved. Some years later, he went 0:08:30.480 --> 0:08:32.800 on to be a part of the co founding team 0:08:33.080 --> 0:08:36.320 at Neuralink and he became the president, and then four 0:08:36.400 --> 0:08:40.920 years ago he left to found his own company, Science Corporation. 0:08:41.320 --> 0:08:44.480 When I visited him at Science Corporation recently, many of 0:08:44.480 --> 0:08:47.880 the things I saw there would have seemed like science 0:08:47.880 --> 0:08:52.080 fiction fantasy just a few years ago. So here's my 0:08:52.160 --> 0:09:00.679 interview with Max Hodak. You started a company called Science Corp, 0:09:00.840 --> 0:09:03.640 which will refer to as Science and tell us about 0:09:03.640 --> 0:09:05.560 science because it's so exciting what you're doing there. 0:09:05.760 --> 0:09:08.839 Our main focus at Sciences is restoring vision to people 0:09:08.840 --> 0:09:10.800 that have gone blind because they've lost the rods and 0:09:10.840 --> 0:09:15.040 cones in the retina. And I this was not something 0:09:15.080 --> 0:09:17.280 I'd not worked on the retina before, but I had 0:09:17.280 --> 0:09:19.720 this thesis that that the technology was there that this 0:09:19.760 --> 0:09:23.880 would be possible. There's I think two different ways to 0:09:23.960 --> 0:09:26.559 do this that people have been thinking about in the retina. 0:09:26.679 --> 0:09:30.560 There's a technical optogenetics, where you use a gene therapy 0:09:30.679 --> 0:09:33.080 to deliver a little bit of DNA to the cells 0:09:33.080 --> 0:09:35.760 of the optic nerve to make them light sensitive. That 0:09:35.760 --> 0:09:37.920 then you could activate with a laser, or you could 0:09:37.960 --> 0:09:40.480 put an electrical stimulator under the retina and drive the 0:09:40.520 --> 0:09:42.719 remaining the cells that are still there electrically. 0:09:43.320 --> 0:09:45.040 And the mean for just one saying, the retina is 0:09:45.080 --> 0:09:47.479 the lawn of cells at the back of the eyeballer 0:09:47.600 --> 0:09:50.440 catching the photons that are coming in through the front. 0:09:50.760 --> 0:09:53.560 And so if you've got a problem where let's say 0:09:53.559 --> 0:09:56.240 those cells have died for whatever reason, lots of reasons, 0:09:56.679 --> 0:09:58.760 then what you're talking about is how do you how 0:09:58.800 --> 0:10:01.520 do you get those cells to catch the photons and 0:10:01.640 --> 0:10:03.600 send their signals back along the optic nerve. 0:10:03.840 --> 0:10:05.720 Yeah, so I think you know to take a step back. 0:10:05.760 --> 0:10:08.000 If you're thinking about getting vision into the brain, there's 0:10:08.000 --> 0:10:09.880 a couple of different places you could think to do it. 0:10:09.920 --> 0:10:11.960 The first is the retina. So the back of the 0:10:12.000 --> 0:10:15.079 eye is the retina, which is this really nice two 0:10:15.160 --> 0:10:17.800 D sheet of neurons and a big cable going into 0:10:17.840 --> 0:10:20.960 the brain. So in some ways this is like a 0:10:21.000 --> 0:10:24.440 really ideal interface to the brain. Evolution has done this 0:10:25.480 --> 0:10:28.439 to give us vision. The first stop of the optic 0:10:28.480 --> 0:10:31.240 nerve out of the eye is a structure in the 0:10:31.360 --> 0:10:34.360 thalamus called the lateral janiculate nucleus, which is a very 0:10:34.360 --> 0:10:37.839 deep structure in the brain. It's very old evolutionarily, and 0:10:38.440 --> 0:10:41.360 there's about one point five million cells in the optic nerve. 0:10:41.520 --> 0:10:45.000 There's about about the same number of cells in the thalamus. 0:10:45.240 --> 0:10:47.920 And then from there you go out to a much 0:10:47.960 --> 0:10:51.400 larger number of neurons in cortex called primary visual cortex. 0:10:51.760 --> 0:10:54.760 And so if you want to supply vision to the brain, 0:10:55.080 --> 0:10:58.880 in some sense synthetically your choices are really in the retina, 0:10:59.000 --> 0:11:02.920 in the in the LGN, or in V one, and 0:11:03.720 --> 0:11:07.920 everywhere past the optic nerve gets much much harder. Nobody 0:11:07.920 --> 0:11:10.440 has ever really shown the restoration of form vision by 0:11:10.480 --> 0:11:13.800 directly stimulating either the LGN or V one. I mean, 0:11:13.800 --> 0:11:16.000 people haven't even really shown the restoration of form vision 0:11:16.000 --> 0:11:19.200 simulating the optic nerve. The device that we're bringing to 0:11:19.240 --> 0:11:21.600 market now that just recently finished to face three clinical 0:11:21.600 --> 0:11:24.720 trial sits under the retina and stimulates a layer of 0:11:24.720 --> 0:11:27.679 cells called the retinal bipolar cells, which are the first 0:11:27.720 --> 0:11:30.680 cells past the rods and cones. And so this is 0:11:30.679 --> 0:11:33.400 really in many ways the first opportunity to get a 0:11:33.480 --> 0:11:36.400 visual signal back into the signaling pathways into the brain. 0:11:36.679 --> 0:11:38.920 So let's back up. So how does your device work. 0:11:39.559 --> 0:11:42.520 So the device is called Prima. It's a pretty cool idea. 0:11:42.600 --> 0:11:45.800 So it's a tiny little solar panel chip about two 0:11:45.840 --> 0:11:49.360 millimeters by two millimeters, so it's really very small, and 0:11:49.960 --> 0:11:51.679 there's if you look. If you look at it, you'll 0:11:51.679 --> 0:11:53.920 see all these little hex grids on it, these little 0:11:53.920 --> 0:11:56.040 hex tiles. Each one of those TXT tiles is a 0:11:56.200 --> 0:11:59.080 photodiode and an electrode. So what we do is you 0:11:59.120 --> 0:12:01.000 implant this under the retina in the back of the 0:12:01.040 --> 0:12:03.440 eye where the rods and concept degenerated, and the patient 0:12:03.480 --> 0:12:06.880 wears glasses that have a laser projector on them, and 0:12:07.440 --> 0:12:11.120 the laser projector projects the scene with laser energy onto 0:12:11.160 --> 0:12:13.800 the implant in the back of the eye, and wherever 0:12:13.880 --> 0:12:17.920 the laser energy is absorbed, it stimulates, and wherever there's 0:12:18.080 --> 0:12:20.560 darkness in the scene that it doesn't. And so this 0:12:20.640 --> 0:12:23.000 is a cool idea because there's no implanted battery, there's 0:12:23.040 --> 0:12:26.800 no wires, there's no PCBs, there's no electronics other than 0:12:26.840 --> 0:12:29.720 this tiny little chip. Because you send it both energy 0:12:29.840 --> 0:12:34.079 and information simultaneously in the laser pulse and so this 0:12:34.160 --> 0:12:35.840 is like, it's tough to imagine how you would do 0:12:35.880 --> 0:12:39.240 this more simply than this. And when you look at 0:12:39.520 --> 0:12:42.000 past devices, so like a little over a decade ago, 0:12:42.000 --> 0:12:45.040 there was a company called Second Site that had a 0:12:45.080 --> 0:12:48.680 retinal stimulator that is probably what people would be most 0:12:48.679 --> 0:12:52.160 famous when people think about retinal prustcs. So it worked 0:12:52.280 --> 0:12:56.679 very differently than than the science prima implant. First of all, 0:12:56.679 --> 0:12:58.480 it targeted a different layer of cells. It targeted the 0:12:58.520 --> 0:13:02.000 optic nerve rather than the bip our cells, which are 0:13:02.040 --> 0:13:05.840 just much harder to stimulate naturalistically in this way. And 0:13:05.920 --> 0:13:09.199 the second is because it wasn't it was a conventional 0:13:09.280 --> 0:13:12.679 electrical implant. You had this big titanium box attached to 0:13:12.720 --> 0:13:14.760 the side of the eye. You had cables going in 0:13:14.920 --> 0:13:18.439 through through the eyeball to power it. This was a 0:13:18.440 --> 0:13:21.400 four and a half hour surgery. Being able to just 0:13:21.480 --> 0:13:25.280 put this little two by two millimeter chip of silicon 0:13:25.800 --> 0:13:28.760 fully wirelessly under the eye with a little inserted tool 0:13:28.880 --> 0:13:31.480 is a totally different game and it's and the clinical 0:13:31.480 --> 0:13:33.720 trial results I think really speak for themselves. The first 0:13:33.800 --> 0:13:36.000 time ever in the history of the world, as far 0:13:36.040 --> 0:13:37.839 as we know, that blind patients have been able to 0:13:37.880 --> 0:13:38.320 read again. 0:13:38.679 --> 0:13:42.160 Oh that's so amazing. So all of the electronics and 0:13:42.200 --> 0:13:44.520 all that stuff is in the glasses themselves, which are 0:13:44.559 --> 0:13:47.480 capturing the scene like a camera and zapping it back 0:13:47.520 --> 0:13:49.520 with a laser to the chip. 0:13:49.640 --> 0:13:52.520 Yeah yeah, powering it, Yeah, basically like a solar cell. 0:13:52.679 --> 0:13:56.080 Congratulations on all your progress with that. It's an incredible device. 0:13:56.400 --> 0:13:56.600 Yeah. 0:13:56.800 --> 0:13:59.600 And also I should say we didn't develop this from 0:13:59.640 --> 0:14:03.120 a scratch ourselves. We acquired this from another company called Pixium, 0:14:03.320 --> 0:14:08.800 which was based in Paris and had done has started 0:14:08.840 --> 0:14:11.560 the clinical trial. Originally the technology came from a I 0:14:11.640 --> 0:14:14.800 love at Stanford scientist Daniel Planker in the Electrical Engineering 0:14:14.800 --> 0:14:17.400 department who came up with the idea, did the early 0:14:17.400 --> 0:14:20.280 work at Stanford that was licensed by Pixium. They started 0:14:20.280 --> 0:14:23.120 the clinical trial which we acquired and have finished and 0:14:23.200 --> 0:14:25.160 finished the clinical trial and to bring in to market. 0:14:25.080 --> 0:14:27.960 Right, I mean, I'm so I'm so jazzed that you 0:14:28.000 --> 0:14:30.480 guys are doing that or bringing it to market and 0:14:30.520 --> 0:14:33.040 making making this across the finish line. So that's what 0:14:33.080 --> 0:14:36.440 you're doing in the retina for people who have lost vision. 0:14:37.680 --> 0:14:42.720 Tell me what you're doing with uh reading from neurons? 0:14:42.880 --> 0:14:46.520 So before just before we get there. So the challenge 0:14:46.840 --> 0:14:50.400 with brain computer interfaces has always been, well several One 0:14:50.440 --> 0:14:52.520 of them is that you know, mother nature has wrapped 0:14:52.560 --> 0:14:55.480 the brain in this armored bunker plating, so it's hard 0:14:55.480 --> 0:14:57.360 to get to. But then when you get in there, 0:14:57.760 --> 0:15:00.600 you've got eighty six billion neurons and you have to 0:15:00.600 --> 0:15:03.840 figure out who's saying what. And the traditional way to 0:15:03.880 --> 0:15:07.280 do this is to dunk an electrode in there, which 0:15:07.680 --> 0:15:10.640 really damages the tissue. So obviously people have been trying 0:15:10.680 --> 0:15:13.240 to make electrodes thinner and thinner. But you've got an 0:15:13.280 --> 0:15:16.600 idea that you're working on which is amazing. Tell us 0:15:16.640 --> 0:15:17.040 about that. 0:15:17.440 --> 0:15:19.800 Yeah, so that I can like, there's no free space 0:15:19.800 --> 0:15:22.240 in the brain. The brain is wet, it squished together. 0:15:23.040 --> 0:15:28.680 Evolution has really compressed as much as much as it 0:15:28.680 --> 0:15:30.960 can into as small a space and an energy budget 0:15:30.960 --> 0:15:34.400 as it possibly can, and so there's there has not 0:15:34.520 --> 0:15:37.040 really left holes that we can take advantage of in there. 0:15:37.320 --> 0:15:40.760 Evolution is extremely good at its job, and there's limits 0:15:40.760 --> 0:15:42.720 how small you can make an electrode. You can't make 0:15:42.840 --> 0:15:48.360 a like one nanometer wire because as a wire, just 0:15:48.400 --> 0:15:52.240 any electrical wire gets smaller, the resistance increases there's just 0:15:52.280 --> 0:15:55.880 real limits how small you can make a recording electrode 0:15:56.040 --> 0:15:59.320 before you lose the ability to distinguish the signal that 0:15:59.520 --> 0:16:03.520 you care the biological activity from the background noise. And 0:16:03.560 --> 0:16:07.040 then on the stimulation side, this is actually worse because 0:16:07.080 --> 0:16:09.240 there's real limits how small you can make a stimulating 0:16:09.240 --> 0:16:12.120 electrode before you start splitting water in the brain and 0:16:12.120 --> 0:16:14.720 producing hydrogen and oxygen, and like, you really don't want 0:16:14.720 --> 0:16:17.520 to be doing this, And so we think about, like, 0:16:17.600 --> 0:16:20.080 what does an ideal neural interface look like. I think 0:16:20.120 --> 0:16:23.080 one of the high level intuitions that I started with was, Yeah, 0:16:23.080 --> 0:16:26.200 the brain is encased in this dark vault of a skull, 0:16:26.720 --> 0:16:28.640 but it has to communicate with the world. 0:16:28.960 --> 0:16:30.720 There's like you, the. 0:16:30.720 --> 0:16:34.040 Brain is not telepathically connected to the outside world. I mean, 0:16:34.040 --> 0:16:36.240 it's also important to realize that you're not seeing the 0:16:36.280 --> 0:16:39.400 world out there, right, You're only ever seeing in perceiving 0:16:39.440 --> 0:16:40.960 information that's arrived at the brain. 0:16:41.360 --> 0:16:42.400 And so how does it get there. 0:16:43.400 --> 0:16:45.280 All of the information that flows in or out of 0:16:45.280 --> 0:16:47.760 the brain flows through a relatively small number of cables. 0:16:48.200 --> 0:16:52.160 There's twelve cranial nerves and thirty one spinal nerves. The 0:16:52.200 --> 0:16:55.960 optic nerve is cranial nerve two. The vestibular cochlear nerve 0:16:55.960 --> 0:16:58.520 that carries hearing in balance is also called nerve eight. 0:17:00.080 --> 0:17:03.920 And kind of thinking about you've got this relatively small 0:17:03.960 --> 0:17:06.200 number of wires, we can think about attaching to those 0:17:06.280 --> 0:17:09.320 like we do for getting vision into the brain through 0:17:09.760 --> 0:17:13.560 the remnants of nerve too. But this also kind of 0:17:13.720 --> 0:17:16.120 got in the back of my mind going this idea 0:17:16.119 --> 0:17:18.560 of can we grow a thirteenth cranial nerve that really 0:17:18.560 --> 0:17:21.679 feels like the ideal neural interface. Biology has given us 0:17:21.680 --> 0:17:24.320 other examples of fiber bundles that get information in and 0:17:24.320 --> 0:17:26.879 out of the brain for really any purpose that the 0:17:26.880 --> 0:17:30.639 brain needs. It, is it possible to add a thirteenth 0:17:30.680 --> 0:17:35.000 biological wire that, instead of having an eye at the 0:17:35.000 --> 0:17:37.359 other end or having a bunch of muscles at the 0:17:37.359 --> 0:17:39.480 other end, had a USBC port basically, And so the 0:17:39.560 --> 0:17:41.600 high level intuition here is like, what can we add 0:17:41.600 --> 0:17:43.520 to the brain? How does the brain do this? Like 0:17:43.560 --> 0:17:45.639 how does nature do this on its own? And the 0:17:45.680 --> 0:17:49.560 answers it uses neurons, And so this kind of prompts 0:17:49.600 --> 0:17:51.600 a question what happens if we add more neurons to 0:17:51.640 --> 0:17:54.000 the brain and the answers, they grow in and wire 0:17:54.119 --> 0:18:00.240 up and give you these bidirectional chemical synapses. And so 0:18:00.320 --> 0:18:03.280 this has led to an approach that we call biohybrid 0:18:04.240 --> 0:18:07.800 like biohybrid neural interfaces, and it really feels like it 0:18:07.840 --> 0:18:11.600 has the scalability that many conventional methods don't. Now there 0:18:11.600 --> 0:18:14.680 are alternatives to electrodes, So tell us what a biohybrid 0:18:14.760 --> 0:18:18.800 interface is. So a biohybrid neural interface is when we 0:18:18.840 --> 0:18:22.840 take heavily engineered stem cell derived neurons in a dish, 0:18:23.160 --> 0:18:27.159 we load those into the electronic device, and then what 0:18:27.200 --> 0:18:30.560 you place into the brain is just the ingrafted cells. 0:18:31.040 --> 0:18:34.040 So we're not placing any metal or any like, no 0:18:34.119 --> 0:18:36.480 electronic or mechanical component goes into the brain. 0:18:36.640 --> 0:18:37.679 Instead, you're growing. 0:18:38.560 --> 0:18:42.960 We basically graft these these cells onto the brain through 0:18:43.560 --> 0:18:46.640 an appropriate starting point, and then those grow out form 0:18:46.680 --> 0:18:50.240 new connections just as kind of more more of the brain. 0:18:50.880 --> 0:18:53.160 And this is because mother nature is really good at 0:18:53.240 --> 0:18:55.959 growing cells into groups of other cells and so on. 0:18:56.000 --> 0:18:57.280 So you're taking advantage of that. 0:18:57.400 --> 0:18:59.680 Yeah, we're letting biology do as much as the heavy 0:18:59.720 --> 0:19:01.960 lifting as we can. Now, this creates other problems, but 0:19:02.560 --> 0:19:04.200 the and I think smart people can say, well, now 0:19:04.240 --> 0:19:07.200 you have a really complicated selling engineering problem to solve. 0:19:07.520 --> 0:19:09.760 But if you can solve that in the meaningful way 0:19:09.840 --> 0:19:12.639 that you have to, yeah, you can get biologies do 0:19:12.640 --> 0:19:13.439 a lot of work for you. 0:19:13.720 --> 0:19:16.679 Yeah. So these cells that you're putting on there and 0:19:16.880 --> 0:19:20.320 growing in you have heavily engineered these cells. So tell 0:19:20.400 --> 0:19:21.240 us about that. Yeah. 0:19:21.280 --> 0:19:22.399 So there's a couple of things you need to do. 0:19:22.760 --> 0:19:24.520 The first is it needs to be matched to the 0:19:24.560 --> 0:19:27.479 immune system. Now, if you don't do this, it's you 0:19:27.520 --> 0:19:30.639 can still make a cell therapy for a patient, but 0:19:30.760 --> 0:19:33.920 you need to do it on an individualized patient basis 0:19:33.960 --> 0:19:37.840 per patient. This is very expensive. It can take a 0:19:37.920 --> 0:19:39.800 very long time to make edit the other edits that 0:19:39.840 --> 0:19:42.560 we need. And so the first set of editing that 0:19:42.600 --> 0:19:46.160 we do is to make the neurons hypommunogenic, meaning that 0:19:46.240 --> 0:19:48.520 they don't bother the immune system when you put them 0:19:48.560 --> 0:19:49.240 in a patient. 0:19:49.359 --> 0:19:50.119 So how do you do that? 0:19:51.520 --> 0:19:54.480 This is a much longer topic. There's these things called 0:19:54.520 --> 0:20:01.200 major histoic compatibility complexes, and we need to suppress some 0:20:01.200 --> 0:20:05.560 protein expression and force some other protein expression to basically 0:20:05.600 --> 0:20:09.719 tell the immune system not to eat you and and 0:20:09.800 --> 0:20:11.040 also that you are fine. 0:20:11.280 --> 0:20:13.359 And how far along are you on that pathway? Is 0:20:13.400 --> 0:20:13.960 that solved? 0:20:14.720 --> 0:20:16.480 I mean, I wouldn't say that that's a solved problem. 0:20:16.520 --> 0:20:20.200 I would say as a as a fields, there's several 0:20:20.359 --> 0:20:24.240 standalone companies that their ip is hypo immune agenic stem cells, 0:20:24.720 --> 0:20:26.920 and so we are i'd say, pretty close to the 0:20:26.960 --> 0:20:30.560 state of the art in the field, but it's not perfect. 0:20:30.840 --> 0:20:31.000 Now. 0:20:31.040 --> 0:20:33.720 In the brain, the immune system tends to leave you 0:20:33.760 --> 0:20:36.680 alone more than many other areas like this is, for example, 0:20:36.760 --> 0:20:38.240 a lot of the work that's been done in gene 0:20:38.240 --> 0:20:40.600 therapy so far has been done in the eye because 0:20:40.880 --> 0:20:43.240 the immune system tends not to overreact in the eye 0:20:43.680 --> 0:20:45.960 because when it does in a patient and a subject 0:20:45.960 --> 0:20:49.359 goes blind, this historically is a bad thing. And so 0:20:49.760 --> 0:20:52.200 there's some areas where you tend to get more autoimmune 0:20:52.200 --> 0:20:55.800 reactions in some are Some are anatomy where this happens less. 0:20:55.920 --> 0:20:58.960 The brain is one of the areas where because around 0:20:59.000 --> 0:21:02.080 the time of the surgery you're treating them with systemic 0:21:03.320 --> 0:21:08.040 immunosuppressants anyway, and then once the bloodburned bearer has healed, 0:21:08.359 --> 0:21:16.720 it being approximately hypominogenic is probably fine. 0:21:25.280 --> 0:21:28.600 Okay, So you do that to these cells, you engineer 0:21:28.640 --> 0:21:31.679 them that way, and then you stick them on so 0:21:31.720 --> 0:21:33.840 that they grow in. But of course you're keeping the 0:21:33.960 --> 0:21:37.160 cell bodies outside and then what are you doing with those? 0:21:37.520 --> 0:21:39.520 Yeah, So the next edit that we make is we 0:21:39.520 --> 0:21:43.760 add a protein called a light gated ion channel also 0:21:43.800 --> 0:21:46.439 as an option to these cells, which allows us to 0:21:46.520 --> 0:21:48.360 fire them using light. 0:21:49.000 --> 0:21:50.240 And this is pretty important. 0:21:50.280 --> 0:21:52.880 So when we have so the device that the cell 0:21:52.960 --> 0:21:56.840 is embedded in has two components around each cell. It 0:21:56.880 --> 0:21:59.720 has a recording electrode which allows us to detect the 0:22:00.080 --> 0:22:02.720 date of the cell, and it has a tiny little 0:22:02.720 --> 0:22:04.800 micro LED kind of like you'd have in like your 0:22:04.840 --> 0:22:08.080 phone screen next to the cell. And so when we 0:22:08.119 --> 0:22:10.280 want to fire a neuron, we turn on the LED 0:22:10.560 --> 0:22:12.680 and that depolarizes the cell and sends a pulse into 0:22:12.720 --> 0:22:15.920 the brain. And when that neuron receives input from the brain, 0:22:15.960 --> 0:22:18.400 because it's grown out both inputs and outputs, we can 0:22:18.400 --> 0:22:20.840 detect that with the electrode, and so being able to 0:22:20.880 --> 0:22:24.240 optically stimulate using light and electrically record use it in 0:22:24.440 --> 0:22:27.840 an electrode. A capacity of electrode allows us to minimize 0:22:27.920 --> 0:22:30.600 crosstalk between these so that we can do them both simultaneously. 0:22:31.280 --> 0:22:33.800 And they're sandwiched in between this. So the cell body 0:22:33.840 --> 0:22:36.040 is sandwiched in between the little light and the little 0:22:36.040 --> 0:22:38.640 recording electrode. And so you can say, for this guy, 0:22:38.680 --> 0:22:40.200 I want to turn him on now, and I want 0:22:40.240 --> 0:22:42.720