#40 - Three Breakthroughs: Brain-Computer Interfaces, Advanced Neural Networks, and Ozempic Trade Update

Today we're trying to crack open the secrets in our little brain, our cerebellum. Let's see where it brings us.

If you do not listen to Steve Jobs and Sam Altman and Elon Musk, you are going to be missing out.

What is deep tech today becomes shallow tech tomorrow, and we actually grow more and more into it. This is no longer just about where you're going for The cheap, yeah, scratch the itch of, you know, the junk food type thing. I mean, it truly is what's going into your body and playing a much bigger role.

All right, hello everyone. Welcome back to this episode of The Tech Optimist, 3 Breakthroughs. We got a cool episode for you today. Today, of course, we're gonna be joined by the legend himself, Mike Collins, founder and CEO here at Alumni Ventures. And we have a new guest for the 3 Breakthroughs for the next 2 episodes. Mike will be joined by Michael Perry, a partner here at Alumni Ventures, But again, we also call him Mike, so this will be interesting. And then of course, myself, Sam Herrick, will be your guide and editor for this episode. In a world captivated by criticism, it's easy to overlook the groundbreaking technologies shaping our future. Let's shine a light on innovators who are propelling us forward. As the most active venture capital firm in the US, we have an exceptional view of tech's real-world impact. Join us as explore, celebrate, and contribute to the stories of those creating tomorrow. Welcome to The Tech Optimist. As a reminder, The Tech Optimist podcast is for informational purposes only. It is not personalized advice, and it is not an offer to buy or sell securities. For additional important details, please see the text description accompanying this episode.

Hi, welcome to Alumni Ventures and our Tech Optimist podcast. This is our 3 Breakthroughs segment where we talk about things that are on our mind, caught our attention, we're thinking about, could be potentially big news in the areas of innovation, technology, or science. I've got a new copilot this week. Mike Perry has volunteered to do this for the next month or so, letting, you know, Matt Caspari, who was doing it, get back to his day job. So, Mike, welcome to the show.

Thanks, Mike. Happy to be here. Really looking forward to it. I've enjoyed listening prior episodes, so hopefully I'll have some cool groundbreaking stuff we could, we could chat about for the next few weeks.

And Mike, you work in our Chicago office with a couple of our good Midwestern funds.

That I do. Chicago born and raised. My parents came over from Italy, found a nice spot here in Chicago, and I've been here ever since. So it's nice. UChicago grad, as you can see behind. My wife was at Northwestern, so we plopped down in Lincoln Park as we were coming down for grad school. Over a decade later, plus 2 kids, here we are. So we're still here enjoying it. And hopefully, you know, we'll make the city work for the long term. But we'll see. Constant debate of do you stay in the city or do you go to the suburbs?

Yeah, I mean, huge Chicago fan. Obviously, it's— for me, it's, you know, definitely one of the top cities in the country.

Yeah, maybe, maybe May through September.

Yeah.

Yeah.

I mean, definitely. Definitely the walk to the office in February can be a little rough. But I live in New Hampshire, so it's— I haven't figured that out yet either. But what great people, cool architecture, food, sports, the lake. What else could you want? Great city. Yeah. So congratulations on that.

Yeah, thanks. I was— we actually, my wife and I with our kids, we were planning to come out more towards the East Coast this week. We have friends near the Providence, Rhode Island, Westport, Massachusetts area. But looks like Hurricane Debbie might be throwing a wrench into that one. Yeah. So rain check, pun intended. We'll have to come back out at another time.

I'm also in the camp. I mean, I mean, you're thinking through it. It's like I'm a big advocate generally of like cities when you're young. suburbs with kids and then get back to the city when they leave the nest.

There you go. Exactly.

All right. Number 1, I've got a little different take on a breakthrough is I'm going to push the Lex Fridman interview this week with Neuralink-themed And, you know, starts off with, I don't know, 90 minutes with Elon Musk. And, you know, Lex does amazing interviews. This one is, I don't know, something like 7 or 8 hours.

Oh my God. A marathon.

Buckle in, right? Yeah. So I had a, you know, I took a long bike ride this weekend and I listened to it like 2x.

Yeah.

So, you know, I have to slow down part of it. I mean, those guys deal at pretty high bandwidth. And so, yeah. And by the way, I was on an e-bike on a rail trail, so don't give me too much credit. But I thought it was fascinating. Again, you know, I think it is really important if you're, you know, at all interested in technology and innovation and investing, You need to listen to people like Elon. And whether you love him or hate him or, you know, like a lot of the people who move society forward, they're jagged and they're, you know, like all of us, flawed. But I think you really, if you do not listen, to Steve Jobs and Sam Altman and Elon Musk and et cetera, Zuck, you know, you are going to be missing out. And so do yourself a favor and listen to this interview.

Ask and you shall receive. So this is one of the first times from combing through the narrative of this episode and trying to dissect and, you know, add any missing pieces to the show, Where Mike and I have had this sort of same breakthrough for the week. I too, a few days ago, was scrolling through YouTube and had this episode from Lex Fridman come up, and I've listened to it already, and it is a really awesome episode. Again, however you feel about Elon, just some of the things that he's saying are always fascinating, and Lex does a fantastic job on his podcast of really being a third-party unbiased view. And interviewer. Like, his podcast is like, some of the stuff that they talk about is very fascinating, very innovative. Like, some examples of some guests he's had on his podcast are Jordan Jonas, Andrew Huberman, Sean Carroll, Mark Zuckerberg, Annie Jacobson, Matthew Cox, Jeff Bezos, Mark Zuckerberg again. Matthew McConaughey, Bert Kreischer, the comedian, David Pakman, Simone Gertz, and the list just goes on and on. Um, but if you want to hear the rest of that episode, you know, go over to his YouTube channel or, uh, on Spotify. It's just the Lex Fridman Podcast. But I'm going to bring you that snippet right here from that episode so you don't have to go anywhere. Um, yeah, here's a snippet from that. And then we will just keep rocking with the rest of the show.

You think there'll be emergent leaps of capability as you scale the number of electrodes? Like there'll be a certain, do you think there'll be like actual number where it just, the, the human experience will be altered? Yes. What do you think that number might be? Whether electrodes or BPS, we of course don't know for sure, but is this 10,000, 100,000?

Yeah, I mean, certainly if you're anywhere at 10,000 bits per second, I mean, that's vastly faster than any human could communicate right now. If you think of the, what is the average bits per second of a human? It is less than 1 bit per second over the course of a day because there are 86,400 seconds in a day and you don't communicate 86,400 tokens in a day. Therefore, your bits per second is less than 1 averaged over 24 hours. It's quite slow. And now even if you're communicating very quickly and you're talking to somebody who understands what you're saying, because in order to communicate, you have to, at least to some degree, model the mind state of the person to whom you're speaking, then take the concept you're trying to convey, compress that into a small number of syllables, speak them, and hope that the other person decompresses them into a conceptual structure that is as close to what you have in your mind as possible.

Yeah. I mean, there's a lot of signal loss there in that process.

Yeah. Very lossy compression and decompression. And a lot of what your neurons are doing is distilling the concepts down to a small number of symbols, of say syllables that I'm speaking, or keystrokes, whatever the case may be. So, That's a lot of what your brain computation is doing. Now, there is an argument that that's actually a healthy thing to do or a helpful thing to do because as you try to compress complex concepts, you're perhaps forced to distill the, you know, what is most essential in those concepts as opposed to just all the fluff. So in the process of compression, distill things down to what matters the most because you can only say a few things. So that is perhaps helpful. I think we might, we'll probably get, if our data rate increases, it's highly probable that we'll become far more verbose. Just like your computer, you know, when computers had like, my first computer had 8K of RAM, you know, so. Mm-hmm. You really thought about every byte. And Now you've got computers with many gigabytes of RAM. So if you want to do an iPhone app that just says, hello world, it's probably, I don't know, several megabytes minimum, a bunch of fluff. But nonetheless, we still prefer to have the computer with the more memory and more compute. So the long-term aspiration of Neuralink is to improve the AI human symbiosis by increasing the bandwidth of the communication. Because even if in the most benign scenario of AI, you have to consider that the AI is simply going to get bored waiting for you to spit out a few words. I mean, if the AI can communicate at terabits per second and you're communicating at bits per second, it's like talking to a tree.

You've talked about the threats, the safety concerns of AI. Let's look at long-term visions. Do you think Neuralink is, in your view, the best current approach we have for AI safety?

It's an idea that may help with AI safety. Certainly not, I wouldn't want to claim it's like some panacea or that it's a sure thing. But I mean, many years ago I was thinking like, well, what would inhibit alignment of human, collective human will with artificial intelligence? And the low data rate of humans, especially our slow output rate, would necessarily just, because it's such a, because the communication is so slow, would diminish the link between humans and computers. Like, the more you are a tree, the less you know what the tree is. Like, let's say you look at a tree, you look at this plant or whatever, and like, hey, I'd really like to make that plant happy, but it's not saying a lot, you know?

So the more we increase the data rate that humans can intake and output, then that means the better, the higher the chance we have In a world full of AGIs.

Yeah. We could better align collective human will with AI if the output rate especially was dramatically increased. And I think there's potential to increase the output rate by, I don't know, 3, maybe 6, maybe more orders of magnitude. So it's better than the current situation.

And that output rate would be by increasing the number of electrodes, number of channels, and also maybe implanting multiple Neuralinks?

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And then the whole area of Neuralink is just fascinating. Obviously, I think they've had 2 or 3 implants already. For those of you that are less familiar with the technology, this is basically dealing kind of with a computer, you know, probes into the brain. They obviously started like a lot of companies do with people that have significant disabilities and limitations. And, you know, it's kind of a miracle what they can provide to people. And just, you know, breaking down with some of the team there, the impacts on people's lives that they're having, the serious technology and engineering going into basically putting this thing in a human brain, their plans for the future. Just really, I think it's hard to come away without huge respect for people who, again, are working on really, really hard problems that seem crazy or way into the future. I mean, in Elon's, you know, Obviously, Tesla, SpaceX, Starlink, Neuralink, you know, big, big problems. And

so, it's the ultimate equalizer, right? Like, you had talked about this where it's like, regardless of your maybe, you know, flavor-of-the-week stance on a certain policy or political leanings, you know, it's undeniable what these entrepreneurs are doing to really better society, better science, better breakthroughs. You know, it's a prime example of it.

I mean, and obviously, you know, everything's a nail with, with, with technology hammer in my hand. But it's like if you step back and you look at how the world has moved over the past thousands of years, the past 100 years, underlying all of it is usually big technology shifts and innovations. And Clearly, we're looking— I think we're looking on a handful of fronts right now where there's stuff going on with energy, there's stuff going on in AI, there's stuff going on in the life sciences space, kind of an ultimate area

of

innovation and technology and venture capital for the next 100— Decades. 200, 300 years, it's going to be— space is going to be increasingly part of the story, I think. But again, I just encourage people, this is an example of the kind of thing that you, you know, you got to at least scan and listen to what, you know, the people that are driving these changes are saying and thinking and working on because it's going to impact your life, the lives of your kids, grandkids, etc., your business, your personal life. Yeah. So that's my pitch.

No, it's great. I mean, you had mentioned this earlier, the notion of deep tech and a lot of these breakthroughs. We're in this privileged seat where we could see all of this stuff. And I think what's really fascinating for folks who aren't as lucky as we are to be engaging with these great entrepreneurs building in deep tech is the natural evolution where what is deep tech today becomes shallow tech tomorrow. And we actually grow more and more into it. And then you just continue to challenge the complacency in terms of what we think is feasible, right? And I think this is a prime example of that. And it's fascinating to see how far we've come. I have less years overall than you have in the venture space, but even the decade plus, right? I mean, the amount of innovation that's happened is truly like sci-fi in that way. Yeah. You don't think it's possible, and then all of a sudden it is, and it becomes part of your status quo.

Yeah, one of our young associates, actually one in the Chicago office, just did an Instagram reel that I thought was really clever, which is taking— Drew took a bunch of technologies, the automobile and the airplane and all of these things, and he pulled quotes about people, a fair number from the New York Times, basically, who was calling all of it just impractical, stupid, niche, just, you know, kind of claim chowder, you know. And, you know, that's the story of technology. You know, first you're crazy and then, you know, it's obvious, right, before you know it. So,

oh yeah, I think about early in my career, Bill Morris from, you know, at the time Google was speaking here in Chicago and he had talked about this notion of exponential growth and just scientific breakthrough. And his example was mapping the human genome.

Yep.

Where you had 2 sides of the camp, right? When we got 1%, you had this vast majority of researchers and scientists who are like, well, you know, it's going to take 100 more years to get the rest. But then you had another side which was like, no, it's going to happen really fast. And sure enough, right, in a matter of years, you know, fully mapped and we're off to the races. So it just goes to show you how exponential that

Well, and I think it shows you too, Mike, on how poor humans are to underappreciating things that are geometric in shape.

Yeah.

I mean, our brains work fairly intuitively in a linear fashion. They do not— part of being a great investor is just understanding the flaws of human biases and the way our brains work. And then, people like Warren Buffett understand these things. I think they're well-read, but I think some of it is also intuitive. And basically, you are about human biases. And one of the things you are about is not appreciating geometric phenomena, right? And so, that's one for sure. So, what do you got?

Yeah, complacency really can be a killer. So, on the notion of You know, brain science. I actually found a really cool one. And fun fact, Mike, I don't know if you knew this about me, graduated in the financial crisis. So right away your job offer, you know, vanishes overnight.

Right.

So I studied behavioral cognitive neuroscience and economics in undergrad. And I was like, well, you know what, maybe, maybe the PhD route is for me. So my first job was a research assistant in a neuroscience lab. It helped me learn data science before data science was a cool thing, but it also just piqued my interest in neuroscience in general. So I read recently, and it was published originally in Nature, you know, a leading scientific journal, but it was picked up on a whole host of different, you know, websites and whatnot, which are, you know, leading neuroscientists today are unlocking the secrets of, quote unquote, your little brain. So your cerebellum. And what's groundbreaking about this is the cerebellum, you know, speaking of complacency, has been originally thought about in terms of the traditional place for coordinating movement.

Mm-hmm.

Right? And a lot of research has been done there, but it's also significantly influencing our thoughts and emotions, you know, where others had thought different areas of the brain. So, like I said, initially published in Nature, and, you know, it really challenges these long-held beliefs about the cerebellum's function. So, you know, when I saw that, I was like, okay, here's an area where you have researchers who are really pushing that complacency and saying like, what else do we know about our brain? Which, you know, too long didn't read for our listeners out there, not much. We're still exploring a lot. Yeah. But, you know, in my mind and what they're seeing in the research is like, it really is revolutionary, right? So although the cerebellum, for those who don't know, it only comprises about 10% of the brain's volume, but it contains over half of all of its neurons.

Yeah.

So I think that in and of itself is really a leading indicator that research is being done there and continue you know, should be being done there to understand what else it does.

Yeah.

So now, this breakthrough is really understanding the notions of its contributions to cognitive processing, emotional regulation, and it suggests just a more integrated role in brain function than previously understood. So, before we go into like some of the potential and why, I just wanted to stop there and, you know, see if you thought it was as cool to you as it was for me.

Yeah, no, super cool. And again, I think there's some intuition there too that resonates, which is so much of great thinking is often associated with kind of physical activity, right? That stress management related to exercise being kind of the silver bullet, the motion, rhythmic motion leading to kind of getting in flow, physical flow, mental flow, those kinds of things, and a very holistic approach for sure. Yeah. Yeah, super interesting. Look forward to reading it. I have not read that.

Yeah. And, you know, for me, we sit back and once again, we have this luxury of being able to look at all this innovation, right? So our team recently sponsored a deal in a micro-robotics platform. They essentially take this little device smaller than the size of a grain of rice and could put drug payloads in there. They go in through the cerebral spinal fluid up into the brain and deliver it. And you think of what this research is coming out and how it can help, you know, innovations like that. So all of a sudden, you have this real new view and, you know, kind of revolutionized understanding of both neurological and psychological disorders that can really help new treatments and therapies. So, you know, by recognizing that the cerebellum has a much broader impact and it is integrated, you know, you think about the innovative approaches to things that society deals with every day and we know is interconnected, things like anxiety or depression or rates of childhood autism, you know, what's going on. So it's really a small step but a big breakthrough in the sense of how can we challenge what we know about certain areas?

Yeah.

And, you know, continue to push that innovation moving forward. So it's one I always in the back burner look at all things breakthrough neuroscience. So I thought this was a No, no,

listen. And, and from the humans are biological computers with our own tech stack. And actually, again, Elon and Lex talk a little bit about this in the, in the first part, which is, you know, you're going to have silicon computers, silicon AIs, you know, robotics over here. And then you have, you know, these big bags of salt water with a biological brain. And how do we work together, right? Yeah. And, you know, and one of the issues is just bandwidth between our brain and those systems. You know, that, that can be— that's a real area of research. That's a real area of potential innovation, I think.

Yeah.

You know, you know, You see a 15-year-old walking around with a smartphone, right? And that is a pretty intimate relationship, frankly. Now, it's a separate device. They're looking at it through their eyes and things like that. But boy, it's pretty inseparable for one. Try to take it away.

And as a As a dad of 2 young little ones, my wife and I talk about that all the time, like the relationship with technology, even from when we're kids to, you know, our kids today. We don't know how to approach it. I think we'll approach it as it comes, but it's certainly something top of mind for us. Yeah.

No, it's— we are already computer-enhanced biological computers, and I think we're just going to see more and more of that.

I really love that Mike P brought this in, in his breakthrough for his first introductory episode. Welcome to the Tech Optimist family, Mike. But what a way to kick off breakthroughs, right? I love how, you know, this paper that he talks about from Nature kind of flips what we know about mental health and physical health. On its head because the cerebellum or the little brain is like so unexplored. So I did a bit of research into this topic recently and I found a few things that I want to share. So published in Nature's Mental Health journal, um, last week, um, an article was published titled Brain Lifestyle and Environmental Pathways Linking Physical and Mental Health. So I'm going to read a bit of the abstract and then go from there. Depression and anxiety are prevalent in people with a chronic physical illness. Increasing evidence suggests that co-occurring physical and mental illness is associated with shared biological pathways. However, little is known about the brain's role in mediating links between physical and mental health. Here, using multimodal brain imaging and organ-specific Physiological markers from the UK Biobank, we established prospective associations between the baseline health of 7 organs, including cardiovascular, pulmonary, musculoskeletal, immune, renal, hepatic, and metabolic systems, and mental health. We revealed multiple pathways mediated by the brain through which poor organ health may lead to poor mental health, We identify lifestyle and environmental factors, including exercise, sedentary behavior, diet, sleep quality, smoking, alcohol intake, education, and socioeconomic status that influence mental health through their selective impact on the physiology of specific organ systems and brain structure. So from there, that got me thinking about, you know, what like all of this means. You know, and what what can happen after those pathways are discovered. And it seems like someone was ahead of us for sure. So I came across a multi-institutional research project led by Todd Braver. The article that I found this is from the Washington University in St. Louis Art and Sciences, and it's called Braver Awarded MURI Grant for Attention Control Strategies Research. So Braver is a professor of psychological and brain systems in art and sciences at Washington University in St. Louis, and the project is a computational cognitive neuroscience framework for attention control traits and states, and it's expected to span about 5 years with a total budget of $8.8 million. The research team will develop neurocomputational models of both individual differences with state-related fluctuations in attention control due to factors such as motivation, stress, and mind wandering, and they will test the models using multimodal neuroimaging methods including functional MRI and EEG. They will also develop novel tasks to investigate attention control in both laboratory and real-world complex environments. So a major goal of the project will be to harness the modeling and task development efforts to implement and evaluate new training strategies for enhancement of attention control. This is what this is quoted from Braver. Such strategies will be useful in enabling individuals to maintain high levels of focus and concentration, even in high-pressure situations such as those faced by military personnel. So this too is kind of diving into. The little brain, right? Like how much of that has contributed to our attention span? How much of that is contributed to our physical health and mental health? Like it's all connected. Um, and so I thought these are really cool. Uh, I'm gonna, you know, throw these articles in the show notes, but wanted to share. We've got, uh, we're gonna take one more ad break and then we're gonna hop into Mike's last breakthrough to round off the episode.

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All right, the last one I've got, I'm going to go to McDonald's.

Okay, here we go.

McDonald's had their earnings, which were pretty poor. I'm being generous, I think.

Not a good week to talk about earnings, right?

Yes, earnings. And I'm going to pick on one company in particular because I think there was a fair amount of misdirection going on. And again, I think everybody that's been around me knows that I think that one of the profound but less spoken about technology breakthroughs is related to GLP-1 drugs.

Yeah.

And we're beginning to— and I think if you really read carefully and see the numbers in the earnings reports, I think we're at the very, very tip of that starting to impact, um, you know, I think Scott Galloway called it like the, the, the fast food industrial complex.

Yeah.

And, you know, I, I, I wrote something a while ago, you know, the Ozempic trade, and, and, and really where I think You have more and more people beginning to take these medications. More and more, they're finding beyond weight loss benefits to inflammation, fatty liver disease, a variety of unweight-related health benefits, maybe even some areas that are affecting other organs like the brain and the kidneys and— Yeah. You know, there's just so much that has been an unintended consequence of industrial food production, which has allowed the population to, you know, greatly expand on our planet. Yeah. And people are not starving. And but again, like every technology, there's a, you know, negative unintended consequence and With an evolution of scarcity and all of a sudden you go into a supermarket and there's a zillion calories and a lot of them are processed and engineered, we clearly statistically have had an obesity epidemic. Yeah. And, there is an entire kind of food system related to cheap, good, Tasty calories. And, you know, again, this—

And cheap calories.

And cheap calories.

They've made it to the point where it's, you know, and this is what's funny. And I think to your point of like, there's something else there potentially in the McDonald's earnings because, you know, it's almost cheaper to go and buy 3 meals a day for your family at McDonald's than to go to a grocery store right now.

It is. Yeah.

I mean, inflation's only playing one part of that. It's much higher in other aspects. So, totally agree. There's something else that could be happening really from a behavioral economics standpoint.

100%. I think that's exactly right. And, but I, and I think what you're going to see over time is I think you're going to see people who recognize that a health Me being healthy and taking a GLP-1 drug is in my self-interest.

Yeah.

And that will mean I— the consequence of that is I'm going to eat more fresh, real food and less McDonald's. And I think, you know, that's a very simple example. And because I'm doing that, I'm going to not become a diabetic and I'm not going to need a stent. And I'm not gonna maybe need knee replacement surgery at 50, but at 70. So I think, again, maybe it's reading my own book, but I, you know, I think it was— I think the call was surprising enough to the negative. And if you really parse it— Yeah. Now, again, I personally felt there was like a lot of jazz hands around stuff going on, but I think that this is, uh, This is the very tip of the iceberg of what we could see over the next decade, which is a real shift. Because if, you know, if these medications become more widely available, which they will, turn into pill form and become more accessible and more affordable, which they will, I think you're going to see pretty dramatic shifts in certain parts of at least the food, the alcohol— Yeah. Again, we're finding, you know, some other behaviors and disorders are helped regulated by some of these systems. And you're going to see a pull-through.

I mean, you know this about me, Mike. I've done a lot in digital health and healthcare investing over the years. And, you know, I think you're starting to see, you know, food as medicine as a new category of care. And it isn't just what consumers are looking for as it relates to their overall healthcare and health positioning. But you're seeing large, you know, health insurers move into, okay, how do we think about this from a reimbursement standpoint? How do we think about this embedded in true value-based care? I mean, this is no longer just about where you're going for the cheap. Yeah. Scratch the itch of, you know, the junk food type thing. I mean, it truly is what's going into your body and playing a much bigger role. And as we unpack, you know, the elements of GLP-1s and other innovation there, I think you're gonna see that pull through in terms of the long-term behavioral component, right? Where it's like, okay, maybe you're down titrating off of that, but now you've built this new mindset where you do recognize food as part of your medicine.

Yeah.

And health insurers of the future will think about, you know, a great preventative care model isn't, you know, surgery or throwing different pharmaceuticals at it, but it's a combined approach where it's, you know, maybe we help subsidize great food for individuals, right? Especially those that are diabetic. So I think we are only stepping into what that paradigm of care looks like and how business models can shift around it.

All right. All right. We've talked about GLP-1 drugs on this podcast Quite a few times. Mike has graciously shared his experience on a GLP-1 drug, Ozempic. But if there are other people out there like me, again, I'll say it again, I might sound like a broken record, but I'm not a neuroscientist. I'm not a doctor. I'm not a biologist. I don't necessarily know how GLP-1 actually works within the body. I know that we did a video a few weeks back with a company called Pendulum, where Colleen Cutcliffe, the CEO of the company, did a really nice job of sort of explaining, you know, what GLP-1 drugs are, how they work in the body. So definitely recommend taking a look at that if you're more interested. But I want to share a quick clip from Andrew Huberman's podcast called From the Huberman Lab. Called What Is GLP-1 and How Does It Reduce Appetite and Promote Weight Loss? Andrew Huberman does an excellent job of explaining scientifically and unbiasedly what this drug does, like biologically and in science terms. So I'm going to play that now because I think it's really fascinating and it sort of helps everyone understand how it's actually working. So hold tight.

I want to highlight some recent findings in an area totally separate from mental health that I think are really important for everyone to know about. This is a paper published in the journal Cell, which is a Cell Press journal, an excellent journal, in fact, one of the 3 apex journals. So for those of you that are curious, papers published in the journal Nature, Science, and Cell are considered the sort of Super Bowl, Stanley Cup, and NBA championships of publishing. And this paper entitled An Interorgan Neural Circuit for Appetite Suppression illustrates a very important principle that I think everyone should know about. And that's the principle of so-called parallel pathways. Parallel pathways, as the name suggests, are pathways, they could be neural pathways or hormonal pathways or otherwise, that operate independently of one another to accomplish a common goal. And what this paper really shows is that there's a set of peptides in the body, and the peptide that I'm referring to today is called GLP-1, glucagon-like peptide 1, and some related peptides. I've talked about these on the podcast before for 2 reasons. First of all, I'm a big proponent and consumer of yerba mate. Yerba mate is a tea that can promote the release of glucagon-like peptide 1, and there are also new prescription drugs that are now hitting the market and for which there are really impressive clinical trials for diabetes and obesity that are essentially glucagon-like peptide-1 stimulators. So they stimulate the release of that, or they are in fact a synthetic version of glucagon-like peptide-1. What is glucagon-like peptide-1? It is a peptide, which is a small little protein that can dramatically suppress appetite. So that's why these drugs are being explored and are showing quite impressive results for things like treatment of type 2 diabetes and other forms of diabetes, as well as obesity. So they lead to weight loss. Now, in terms of the yerba mate stimulation of glucagon-like peptide-1, that's going to be a much lower amount of glucagon-like peptide-1 that's released from drinking yerba mate, as opposed to, say, taking a drug that stimulates GLP-1 or taking a drug that is GLP-1. Nonetheless, I should also point out that Yerba mate comes in a bunch of different forms. There is some concern about certain smoky-flavored forms of yerba mate being carcinogenic, so that's why I avoid those forms of yerba mate. But for me, yerba mate is one of the preferred sources of caffeine for me. I like the way it tastes. It does provide that sort of caffeine kick that I like to have early in the day for focus and for work and for exercise. And yet I actively avoid the smoked varieties of yerba mate because of the, potential carcinogenic effects of the smoked varieties. Glucagon-like peptide-1, as I mentioned earlier, can suppress appetite, but what this paper shows is it does that by at least 2 mechanisms through parallel pathways. What this paper shows is that glucagon-like peptide-1 acts on receptors in the body in a portion of the nervous system called the enteric nervous system, E-N-T-E-R-I-C, enteric nervous system. This is a component of your nervous system that you don't really have control It's autonomic or automatic. GLP-1 binds to what are called intestinofugal enteric neurons. You don't need to know the name, but those neurons do 2 things. First of all, they cause some gut distension, so they actually make you feel full. This is incredible, right? A peptide, not actual physical food, but a peptide that stimulates neurons that cause changes in the so-called mechanoreceptors of the gut, of the enteric nervous system, and make people feel full. So it can lead to actually mild, or I suppose if levels of GLP-1 are very high, to major gut distension, okay? I think that the levels of GLP-1 that would come from drinking yerba mate and hopefully from appropriate dosaging of the synthetic forms of GLP-1 or drugs that stimulate GLP-1 would cause mild, not major gut distension, 'cause major gut distension would be uncomfortable. So GLP-1 is acting at the level of gut, To increase gut distension, and by way of a pathway that goes from the gut up to the hypothalamus, this little cluster of neurons about the size of a marble that sits above the roof of your mouth, is also suppressing appetite through brain mechanisms. So this is really beautiful, right? You have a peptide, a small little protein that's released in the gut, and that release within the gut causes gut distension, which makes you feel full, and by way of neural stimulation of the hypothalamus, also activates neural pathways within the brain that trigger satiety, the feeling of having had enough food. So to me, GLP-1 is both impressive and important. Why? Because this recent category of drugs that's now hitting the market seems to adjust obesity or can help people with weight loss in order to help their health, and it's doing so by at least 2 mechanisms. One is within the brain and the other is within the gut and communication through the so-called gut-brain axis, because again, these enteric neurons are communicating to the brain, the hypothalamus, by way of this, what's called the sympathogastric spinal reticular hypothalamic pathway. You absolutely do not need to know all of that. That's a mouthful. That's enough to make your mouth feel distended. But at the same time, things like yerba mate, and I'm sure there are other compounds out there as well, but certainly yerba mate can stimulate the release of GLP-1. So for those of you that are looking for some mild appetite suppression and want to accomplish that while also ingesting caffeine, yerba mate might be a good option for that. And just know that it's operating through 2 mechanisms, on the body through mild gut distension to make you feel full, and on the brain to increase satiety or make you feel less hungry. And then for everybody, not just those that are interested in appetite suppression, I think it's important to understand that these parallel pathways are fundamental to how we are organized. Another good example of this would be when we are excited by something, positive or negative, so it could be stressful, or we're positively aroused, there is a parallel activation of epinephrine, adrenaline, both from your adrenals and from an area in the brain called the locus coeruleus. So again and again, we see this in biology and in neuroscience, that your brain and your body are acting in concert. They're acting together through mechanisms that either are independent, so separately in the brain and separately in the body, but directed towards a common goal, or through communication between brain and body. Almost always, that communication is going to be bidirectional, body to brain and brain to body. So I think these results are really interesting and really important for sake of weight loss, for sake of appetite suppression, and just generally for the way that they illustrate this very important theme of the way that we are constructed at a biological level, which is parallel pathways.

Yeah. And clearly, in both these areas of brain science and AI and the Ozempic trade, we definitely put our money where our mouth is whenever we can. We see a great entrepreneur, a great opportunity, it's consistent with these themes, we look to invest in it. I mean, we're backing just on this particular topic, We've got a great team, super credentialed academically, really working on kind of a non-pharmaceutical approach, working with, you know, a person's own gut biome.

Yep.

And, how can we produce more of, you know, the GLP-1, address issues there kind of just through, you know, The stuff we're growing in our own biome and gut science and those kinds of things. So again, much more holistic, much more about empowering the individual, distributed, information-intensive, disruptive new models. Again, good stuff. Yeah. Just lean into the future, lean into optimism. Hardworking, smart people making the world better.

So, yeah, for sure.

Excellent. Mike, welcome to the show. Look forward to next week. We'll do it again.

Likewise. Talk to you, Mike.

Excellent.

All right.

See you.

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