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

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

Michael Peri:
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, yes, scratch the itch of the junk food type thing. I mean, it truly is what's going into your body and playing a much bigger role.

Samantha Herrick:
All right. Hello everyone. Welcome back to this episode of the Tech Optimist Three Breakthroughs. We got a cool episode for you today. Today of course, we're going to be joined by the legend himself, Mike Collins, Founder and CEO here at Alumni Ventures. We have a new guest for the Three Breakthroughs for the next few episodes. Mike will be joined by Michael Peri, a partner here at Alumni Ventures. But again, we also call him Mike, so this will be interesting. 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 we 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's not an offer to buy or sell securities. For additional important details, please see the text description accompanying this episode.

Mike Collins:
Hi, welcome to Alumni Ventures and our Tech Optimist podcast. This is our Three 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 co-pilot this week. Mike Peri has been volunteered to do this for the next month or so, letting Matt Caspari who is doing it, get back to his day job. Mike, welcome to the show.

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

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

Michael Peri:
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. It's nice. U Chicago grad, as you could 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 two kids, here we are. We're still here enjoying it and hopefully 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?

Mike Collins:
Yeah, I mean, huge Chicago fan obviously. For me, it's definitely one of the top cities in the country.

Michael Peri:
Maybe May through September this week.

Mike Collins:
Yes, definitely the walk to the office in February can be a little rough, but I live in New Hampshire, so I haven't figured that out yet either. What great people, cool architecture, food, sports, the lake, what else could you want? Great city. Congratulations on that.

Michael Peri:
Yeah, thanks. 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 wrench into that one. Yeah, so rain check, pun intended. We'll have to come back out at another time.

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

Michael Peri:
There you go. Exactly.

Mike Collins:
All right, number one 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 starts off with, I don't know, 90 minutes with Elon Musk. Lex does amazing interviews. This one is, I don't know, something like seven or eight hours.

Michael Peri:
Oh, my God. It's a marathon.

Mike Collins:
Buckle in type of thing. I took a long bike ride this weekend and I listened at 2X. I have to slow down part of it. I mean, those guys deal at pretty high bandwidth. 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, I think it is really important if you're at all interested in technology and innovation and investing, you need to listen to people like Elon whether you love him or hate him.
Like a lot of the people who move society forward, they're jagged and they're, like all of us, flawed. I think if you do not listen to Steve Jobs and Sam Altman and Elon Musk, et cetera, Zuck, you are going to be missing out. Do yourself a favor and listen to this interview.

Samantha Herrick:
Ask and you shall receive. This is one of the first times from coming through the narrative of this episode and trying to dissect and any missing pieces to the show where Mike and I have had the 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. 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. Lex does a fantastic job on his podcast of really being a third party unbiased view and interviewer. His podcast is like... Some of the stuff that they talk about is very fascinating, very innovative. 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. The list just goes on and on.
If you want to hear the rest of that episode, go over to his YouTube channel or on Spotify. It's just the Lex Fridman Podcast. I'm going to bring you that snippet right here from that episode so you don't have to go anywhere. Here's a snippet from that and then we will just keep rocking with the rest of the show.

Lex Fridman:
You think there'll be emergent leaps of capability as you scale the number of electrodes? There'll be a certain... Do you think there'll be an actual number where just the human experience will be altered?

Elon Musk:
Yes.

Lex Fridman:
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?

Elon Musk:
Yeah, certainly if you're anywhere at 10,000 plus per second, that's vastly faster than any human can communicate right now. If you think of what is the average per second of a human, it is less than one 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 one 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.

Lex Fridman:
Yeah, there's a lot of signal loss there in that process.

Elon Musk:
Very lossy compression and decompression. A lot of what your neurons are doing is distilling the concepts down to a small number of syllables that I'm speaking or keystrokes, whatever the case may be. 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 what is most essential in those concepts as opposed to just all the fluff.
In the process of compression, you distill things down to what matters the most because you can only say a few things. That is perhaps helpful. I think we will probably get... If our data rate increases, it's highly probable it will become far more verbose. Just like your computer, when computers had... My first computer had 8K of RAM, so you really thought about every byte. Now you've got computers with many gigabytes around. 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.
Nonetheless, we still prefer to have the computer with more memory and more compute. The long-term aspiration of Neuralink is to improve the AI human symbiosis by increasing the bandwidth of the communication. Even 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. If the AI can communicate at terabits per second and you're communicating at bits per second, it's like towing a tree.

Lex Fridman:
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?

Elon Musk:
It's an idea that may help with AI safety, certainly. I wouldn't want to claim it's some panacea or it's a sure thing, but 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 the communication is so slow, would diminish the link between humans and computers. The more you are a tree, the less you know what the tree is. Let's say you look at this plant or whatever, and "Hey, I'd really like to make that plant happy," but it's not saying a lot.

Lex Fridman:
The more we increase the data rate that humans can intake and output, then that means the higher the chance we have in a world full of AGI's.

Elon Musk:
Yeah, we could better align collective human will with AI if the output rate especially was dramatically increased. I think there's potential to increase the output rate by, I don't know, three, maybe six, maybe more orders of magnitude. It's better than the current situation.

Lex Fridman:
That output rate would be by increasing the number of electrodes, number of channels, and also maybe implanting multiple Neuralinks.

Elon Musk:
Yeah.

Matt Caspari:
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Mike Collins:
Then the whole area of Neuralink is just fascinating. Obviously, I think they've had two or three implants already. For those of you that are less familiar with the technology, this is basically dealing with a computer probes into the brain. They obviously started, like a lot of companies do with people that have significant disabilities and limitations, and it's a miracle what they can provide to people.
Just 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. In Elon's obviously Tesla, SpaceX, Starlink, Neuralink, big, big problems.

Michael Peri:
It's the ultimate equalizer. You had talked about this where it's like regardless of your maybe Flavor of the Week stance on a certain policy or political leanings, it's undeniable what these entrepreneurs are doing to really better society, better science, better breakthroughs. It's a prime example of it.

Mike Collins:
Obviously, everything's a nail with technology, hammer in my hand. If you step back and you look at how the world has moved over the past thousands of years, the past hundred years, underlying all of it is usually big technology shifts and innovations. Clearly, I think we're looking at 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, an ultimate area of innovation and technology and venture capital for the next 100, 200, 300 years. Space is going to be increasingly part of the story, I think.
Again, I just encourage people, this is an example of the kind of thing that you got to at least scan and listen to what 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, et cetera, your business, your personal life. That's my pitch.

Michael Peri:
No, it's great. You had mentioned this earlier in notion of deep tech and a lot of these breakthroughs. We're in this privileged seat where we could see all of this stuff. I think what's really fascinating for folks who aren't as lucky as we are to be engaging with these great entrepreneurs, building a 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. Then you just continue to challenge the complacency in terms of what we think is feasible.
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, the amount of innovation that's happened is truly sci-fi in that way. You don't think it's possible and all of a sudden it is and it becomes part of your status quo.

Mike Collins:
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-y, just claim chowder. That's the story of technology. First you're crazy, and then it's obvious before you know it.

Michael Peri:
Oh, yeah. I think about early in my career, Bill Morris from... At the time, Google was speaking here in Chicago, and he had talked about this notion of exponential growth, just scientific breakthrough. His example was mapping the human genome where you had two sides of the camp. When we got 1%, you had this vast majority of researchers and scientists are like, "Well, it's going to take 100 more years to get the rest." Then you had another side which was like, "Now it's going to happen really fast." Sure enough, in a matter of years, fully mapped and we're off to the races. It just goes to show you how exponential that can really be.

Mike Collins:
I think it shows you too, Mike, on how poor humans are to under-appreciating things that are geometric in shape. Our brains work fairly intuitively in a linear fashion. Part of being a great investor is just understanding the flaws of human biases and the way our brains work. People like Warren Buffett understand these things. I think they're well-read, but I think some of it is also intuitive. Basically, you are about human biases. One of the things you are about is not appreciating geometric phenomena. That's one, for sure.

Michael Peri:
Complacency really could be a killer. On the notion of 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 vanishes overnight. I studied behavioral cognitive neuroscience and economics in undergrad, and I was like, "Well, you know what? Maybe the PhD route is for me." 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.
I read recently, and it was published originally in Nature, a leading scientific journal, but it was picked up on a whole host of different websites and whatnot, which are leading neuroscientists today are unlocking the secrets of "your little brain," so your cerebellum. What's groundbreaking about this is the cerebellum, speaking of complacency, has been originally thought about in terms of the traditional place for coordinating movement. A lot of research has been done there, but it's also significantly influencing our thoughts and emotions where others have thought different areas of the brain are.
Like I said, initially published in Nature. It really challenges these long held beliefs about the cerebellum's function. When I saw that, I was like, "Okay, here's an area where you have researchers who are really pushing that complacency and saying, 'What else do we know about our brain?'" Which too long didn't read for our listeners out there, not much. We're still exploring a lot of it. In my mind, and what they're seeing in the research is, it really is revolutionary.
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. I think that in and of itself is really a leading indicator that research is being done there and continue should be being done there to understand what else it does. 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.
Before we go into some of the potential and why, I just wanted to stop there and you [inaudible 00:24:00] cool to you as it was for me?

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

Michael Peri:
For me, we sit back and once again, we have this luxury of being able to look at all this innovation. 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, and they go in through the cerebral spinal fluid up into the brain and deliver it. You think of what this research is coming out and how it can help innovations like that, so all of a sudden you have this real new view and revolutionized understanding of both neurological and psychological disorders that can really help new treatments and therapies.
By recognizing that the cerebellum has a much broader impact and it is integrated, 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, what's going on. It's really a small step, but a big breakthrough in the sense of how can we challenge what we know about certain areas and continue to push that innovation moving forward. It's one I always in the back burner look at all things breakthrough neuroscience. I thought this was a really cool one.

Mike Collins:
No, no. Listen, 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 first part, which is you're going to have silicon computers, silicon AIs, robotics over here, and then you have these big bags of salt water with a biological brain and how do we work together?
One of the issues is just bandwidth between our brain and those systems. That's a real area of research. That's a real area of potential innovation, I think. You see a 15-year-old walking around with a smartphone, 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.

Michael Peri:
As a dad of two young little ones, my wife and I talk about that all the time. The relationship with technology, even from when we're kids to 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.

Mike Collins:
Yeah, no, we are already computer-enhanced biological computers, and I think we're just going to see more and more of that.

Michael Peri:
Yeah.

Samantha Herrick:
I really love that Mike P. brought this in his breakthrough for his first introductory episode. Welcome to the Tech Optimist family, Mike, but what a way to kick off breakthroughs. I love how this paper that he talks about from Nature flips what we know about mental health and physical health on its head because the cerebellum, the little brain, is so unexplored. I did a bit of research into this topic recently, and I've got a few things that I want to share.
Published in Nature's Mental Health Journal last week, an article was published titled Brain Lifestyle and Environmental Pathways, Linking Physical and Mental Health. 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 seven 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."
From there, that got me thinking about what all of this means and what can happen after those pathways are discovered. It seems like someone was ahead of us, for sure. 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. 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.
It's expected to span about five years with a total budget of $8.8 million. The research team will develop neuro computational models of both individual differences with state-related fluctuations in attention control due to factors such as motivation, stress, and mind wandering. They will test the models using multimodal neuroimaging methods, including functional MRI and EEG. They'll also develop novel tasks to investigate attention control at both laboratory and real world complex environments.
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 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 diving into the little brain. How much of that is contributed to our attention span? How much of that is contributed to our physical health and mental health? It's all connected.
I thought these were really cool. I'm going to throw these articles in the show notes, but wanted to share. We're going to take one more ad break and then we're going to hop into Mike's last breakthrough to round off the episode.

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

Michael Peri:
Okay. Here we go.

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

Michael Peri:
Not a good week to talk about earnings, right?

Mike Collins:
Yes, earnings. I'm going to pick on one company in particular because I think there was a fair amount of misdirection going on. 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-I drugs. We're beginning to... 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, I think Scott Galloway called it, the fast food industrial complex.
I wrote something a while ago, the Ozempic trade, 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 un-weight-related health benefits, maybe even some areas that are affecting other organs like the brain and the kidneys. There's just so much that has been an unintended consequence of industrial food production, which has allowed the population to greatly expand on our planet. People are not starving.
Again, like every technology, there's a negative unintended consequence. 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. There is an entire food system related to cheap, good, tasty calories. Again, this-

Michael Peri:
And cheap calories, right, too.

Mike Collins:
And cheap calories.

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

Mike Collins:
Yes, it is.

Michael Peri:
Inflation is only playing one part of that. It's much higher in other aspects. Totally agree. There's something else that could be happening really from a behavioral economic standpoint.

Mike Collins:
I think that's exactly right. I think what you're going to see over time is I think you're going to see people who recognize that me being healthy and taking a GLP-I drug is in my self-interest. The consequence of that is I'm going to eat more fresh, real food and less McDonald's. I think that's a very simple example. 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 going to maybe need knee replacement surgery at 50, but at 70.
I think, again, maybe it's reading my own book, but I think the call was surprising enough to the negative if you really parse it. Again, I personally felt there was a lot of jazz hands around stuff going on, but I think that this is the very tip of the iceberg of what we could see over the next decade, which is a real shift because 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.
Again, we're finding some other behaviors and disorders are help-regulated by some of these systems.

Michael Peri:
You're going to see a pull-through. You know this about me, Mike, I've done a lot in digital health and healthcare investing over the years, and I think you're starting to see food as medicine as a new category of care. It isn't just what consumers are looking for as it relates to their overall healthcare and health positioning, but you're seeing large 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?
This is no longer just about where you're going for the cheap, yeah, scratch the itch of the junk food type thing. It truly is what's going into your body and playing a much bigger role. As we unpack the elements of GLP-Is and other innovation there, I think you're going to see that pull through in terms of the long-term behavioral component 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 and health insurers of the future will think about a great preventative care model isn't a surgery or throwing different pharmaceuticals at it, but it's a combined approach where maybe we help subsidize great food for individuals, especially those that are diabetic.
I think we are only stepping into what that paradigm of care looks like and how business models can shift around it.

Samantha Herrick:
All right. All right. We've talked about GLP-I drugs on this podcast quite a few times. Mike has graciously shared his experience on a GLP-I drug, Ozempic. If there are other people out there like me, again, I'll say it again, I might sound like a broke record, but I'm not a neuroscientist. I'm not a doctor, I am not a biologist. I don't necessarily know how GLP-I 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 explaining what GLP-I drugs are, how they work in the body. Definitely recommend taking a look at that if you're more interested. I want to share a quick clip from Andrew Huberman's podcast called From the Huberman Lab called What is GLP-I 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 biologically and in science terms. 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. Hold tight.

Andrew Huberman:
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 the Cell Press Journal, an excellent journal. In fact, one of the three Apex journals. 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.
This paper entitled An Inter-organ 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. 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-I, Glucagon-like Peptide-I, and some related peptides.
I've talked about these on the podcast before for two 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-I, 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-I stimulators. So they stimulate the release of that, or they are in fact a synthetic version of Glucagon-like Peptide-I.
What is Glucagon-like Peptide-I? It is a peptide, which is a small little protein, that can dramatically suppress appetite. That's why these drugs are being explored and are showing quite impressive results for things like treatment of Type-II diabetes and other forms of diabetes as well as obesity. They lead to weight loss. Now in terms of the yerba mate stimulation of Glucagon-like Peptide-I, that's going to be a much lower amount of Glucagon-like Peptide-I that's released from drinking yerba mate as opposed to say, taking a drug that stimulates GLP-I or taking a drug that is GLP-I.
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. That's why I avoid those forms of yerba mate. 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-I, as I mentioned earlier, can suppress appetite. But what this paper shows is it does that by at least two mechanisms through parallel pathways. What this paper shows is that Glucagon-like Peptide-I 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 over. It's autonomic or automatic. GLP-I binds to what are called intestinofugal enteric neurons. You don't need to know the name, but those neurons do two things.
First of all, they cause some gut distension, so they actually make you feel full. This is incredible. 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. It can lead to actually mild or I suppose if levels of GLP-I are very high to major gut distension. I think that the levels of GLP-I that would come from drinking yerba mate and hopefully from appropriate dosaging of the synthetic forms of GLP-I, or drugs that stimulate GLP-I would cause mild not major gut distension because major gut distension would be uncomfortable.
GLP-I 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. This is really beautiful. 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.
To me, GLP-I is both impressive and important. Why? Because this recent category of drugs that's now hitting the market seems to adjust obesity or it can help people with weight loss in order to help their health. It's doing so by at least two mechanisms. One is within the brain and the other is within the gut and communication through the so-called gut-brain access, because again, these enteric neurons are communicating to the brain, the hypothalamus, by way of this what's called the sympathogastro-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.
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-I. 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. Just know that it's operating through two 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.
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. 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. And almost always that communication is going to be bidirectional, body-to-brain and brain-to-body. 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 of the way that we are constructed at a biological level, which is parallel pathways.

Mike Collins:
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 are backing just on this particular topic. We've got a great team, super credentialed academically, really working on a non-pharmaceutical approach, working with a person's own gut biome, and how can we produce more of the GLP-I address issues there just through the stuff we're growing in our own biome and gut science and those kinds of things.
Again, much more holistic, much more about empowering the individual, distributed, information intensive, disruptive new models. Again, good stuff. Just lean into the future, lean into optimism, hardworking, smart people, making the world better.

Michael Peri:
For sure.

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

Michael Peri:
Yeah, likewise. Talk to you, Mike.

Mike Collins:
Excellent.

Michael Peri:
All right, see you.

Mike Collins:
Bye.

Samantha Herrick:
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