66: Biotech, the Immune System and Learning with Trevor klee

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Hosted by
Will Jarvis

In this episode, I’m joined by Trevor Klee. Trevor is a biology autodidact, who has started the biotech https://highwaypharm.com/. We discuss, the difficulties in building a small biotech company, what we know about learning and test prep, the unique immune systems of bats, and a whole lot more. 

The immune system of bats.

Highway Pharm.

Will Jarvis 0:05
Hey folks, welcome to narratives. narratives is a podcast exploring the ways in which the world is better than in the past, the ways that is worse in the past towards a better, more definite vision of the future. I’m your host, William Jarvis. And I want to thank you for taking the time out of your day to listen to this episode. I hope you enjoy it. You can find show notes, transcripts and videos at narratives podcast.com.

Well, Trevor, how are you doing tonight?

Trevor Klee 0:45
I am doing well. Are you doing?

Will Jarvis 0:47
Doing good doing good. Thank you so much for taking the time to hop on with me. I really appreciate it. Before we hop into some of the questions I have, do you mind given kind of a brief bio bio and some of the big things you’re interested in?

Trevor Klee 1:01
Yeah, sure. So my name is Trevor Klee I’m, I’m a Boston, Massachusetts, I have two very disparate job titles right now. So I currently both run a small education business doing Test Prep. So books, I have an app, tutor people have YouTube videos. So that’s one thing that I do. And then I’m simultaneously trying to get a pharmaceutical startup off the ground. I’m looking to do a therapeutic for autoimmune and neurodegenerative diseases. So it’s a maybe, maybe one of the stranger side hustles that people tend to have. Hopefully, it’s soon a full time hustle. That’s awesome. Yeah, I’m interested in stuff relating to both of those.

Will Jarvis 1:59
Gotcha, do you, you know, they sound disparate. But do you see those two is connected in any way? Or is it something you know, you know, Test Prep has been paying the bills, and you want to, you know, this is what you’ve been thinking about for a while? Is pharma? Yeah.

Trevor Klee 2:13
So they’re not particularly connected, I would say like the people in the test prep world who I talked to, literally, none of them have any interest in this. And vice vice versa for pharma. So there’s little to no connection on, the closest connection I actually can make is I taught philosophy for like, a year and a half, to like, Chinese college students as sort of like a strange job that I had. And that sort of got me down the process of like, more researching on my own after college. And I think that was the closer to connection to this farmer stuff. But again, it’s a very weak connection, I can’t make a very strong claim as to how exactly I became interested in these two things.

Will Jarvis 3:04
That’s awesome. That’s awesome. And do you have a bio background at all? Are you just like, sounds like you’ve done a lot of reading. He found some interesting areas, and perhaps found a $20 bill on the sidewalk that people have missed.

Trevor Klee 3:16
Yeah, yeah. So I am in college, I did research into Earth Sciences. I did research into climate change and hurricanes specifically. And then yeah, no, that was that was pretty much it for the scientific background. I took one molecular biology class in college and everything else since then, has been self taught. I will say, My brother has his own pharma startup, which is actually much further along than mine. They’re just submitted an application for drug approval that FDA actually which is awesome. You know, many millions of dollars down the line. Yeah, yeah. It’s big deal. It’s very exciting. So I, you know, I spent a long time talking with him and his business partner about these sorts of things. So it wasn’t entirely foreign to me. I saw him go through. But of course, it’s really different when to go through it yourself.

Will Jarvis 4:18
No doubt. No doubt. That’s really cool. First question, Test Prep. Yeah, I’m curious. And we can we can absolutely cut this if you want to. But for my curiosity, you know, I’ve always envisioned a lot of the standardized tests is kind of like fairly pure test of cognitive stability. Can you get better at them if you’re more familiar with them?

Trevor Klee 4:40
Oh, completely. Yeah. The idea that you can’t is is a lie spread by the test prep companies because your tests of cognitive ability. I mean, it’s, it’s like chess, you know, where you start from and how fast you learn has something to do with cognitive ability. But like, you know, a total idiot who spent, you know, five years studying chess intensively is going to be a genius who never played chess before? I mean, yeah, there’s a lot of crystallized knowledge that goes into it. Gotcha. Um, and that’s, you know, same thing with these tests. Smart people will have an advantage coming into it, and they’ll have an advantage if they studied, but there’s so much crystallized knowledge that goes into it.

Will Jarvis 5:28
Gotcha. That’s super interesting. And are some tests, you know, more proud of that than others? Like, are some like, Is there any anything like that you found?

Trevor Klee 5:38
Um, so the biggest distinction between tests, which is generally a distinction between subjects that people don’t pay enough attention to is skills versus content? Okay, um, so me on to the test I teach are like the MCAT. Now set, yeah, I’ll set to go to law school, go to medical school. I’m the Elsa that is purely skill based, like, you know, you can go into it and score presumably even a perfect score, never having taken it before, if you think about it the right way. Gotcha. Meanwhile, the MCAT is heavily heavily content based, like, you know, I usually tell people, they’re going to study for around 300 hours before they ever are ready to take a practice test. Oh, wow. That’s a ton of content. It’s a huge amount. And so it is, that’s this single biggest difference, and the way you need to approach it really changes pretty dramatically. Which is why, you know, there’s a lot of people who are smart at math, but dumb in history, or vice versa, you know, it’s question of skills versus content.

Will Jarvis 6:51
Gotcha. That’s super interesting. super interesting. And how has it been developing the tutoring business over time? Has it ever been something where you thought this to be a fun thing to do and get into it? Or is it just like a kind of emergent thing where, you know, maybe helps one person and then it kind of took over, because it pretty good at

Trevor Klee 7:12
a, it became a thing, like I was unemployed after college, and I think pretty quickly realized that I’m probably not employable. Like I like, as someone who hasn’t had a traditional grad, like very few traditional jobs in my life, and, you know, sort of stopped having traditional jobs. Six months after college, I got fired from a lot of jobs, like, you know, either fired or not asked back. So I think like the whole I needed something that would pay my rent. And this was something that I enjoyed and was good at. But ya know, from the very beginning, it was like, wow, I really need to pay rent, right?

Will Jarvis 8:01
Like a hard date. That’s a super interesting. I wanted to shift gears a little bit. Why do Biggs species tend to live longer than smaller species? And why does this carry over to like dog breeds?

Trevor Klee 8:13
I don’t understand how that’s a shifting gears at all that goes directly. Direct segue. Yeah. Yeah, so this was the subject of a blog post there. Um, so the the start of the blog post was sort of this. I always like starting things with sort of, like simple observations. And that’s like, I think, in general, the way I view a lot of bio is there’s so much that we don’t know. And I think it’s most interesting to start with a weird observation and be like, Huh, that’s neat. Then you explore and you say why? So? Yeah, this sort of weird observation I started with is, you know, between species bigger species lived longer than smaller species. You know, elephants live longer than mice. You know, whales will live longer than dolphins. Um, you know, that’s, that’s pretty much universal. There are rare exceptions, right? Like humans live exceptionally long naked mole rats live exceptionally long. Bats live exceptionally long, you know, compared to their size, right? But generally speaking, that’s the pattern. And now within a species that’s not true on bigger species of horse like a given a single horse, a bigger variety is going to live less long the smaller variety, you know, a chihuahua is going to live longer than a St. Bernard. You know, Great Danes are sort of famously like their heartbreak dogs, they live till they’re like seven years old. So you’ve got this like question of like, why, you know, does an elephant lived longer than a mouse, but a St. Bernard live shorter than a chihuahua? So that was sort of my like, initial question. Um, and I found a lot of really unsatisfactory answers to it. Like There’s one like weirdly common answer that’s like number of heartbeats. Like,

Will Jarvis 10:07
like Buzz Aldrin, like you’ve only got a certain amount and what’s part of all that? You’re done?

Trevor Klee 10:12
Yeah, yeah. Yeah, I remember there was like a Dilbert comic at some point where they like, I think Gilbert was arguing that like, he only gets a million heartbeats. So he should size. Exactly, no more of them. Yeah. So and So yeah, so I was, I was really unsatisfied with dancers, I found, um, I thought it was easier to explain why an St. Bernard would live less long than a Chihuahua, which is just mainly mechanical stress on heart, right. There’s more body surfaces more chance to get infections, you know, there’s more chance for cancer when you have more cells. So that made sense. The question was, then why do elephants live longer than mice? Um, and so you can answer it from two perspectives. One, you can answer it from an evolutionary perspective, you can say, Why do elephants live longer than mice? Because the evolutionary strategy of the mouse is have lots of kids very quickly, sort of, like, you know, then spend all of your evolutionary energy in like two years, just have like a really rapid generation and, you know, elephants are case selected, as they call it, you know, let’s have one kid every once in a while and put a ton of energy into that kid, right? But that doesn’t really explain how there’s not really a mechanical answer. So mechanically, it came down, this is where it gets a little fuzzier, but mechanically, I believe it comes down to the immune system. Um, and so and that’s, you know, the immune system, as you can probably tell, is something that I find super interesting, I’ve come back to it in various forms, like getting together, mainly. Sorry about that is my dog is playing with bone. The immune system. The way I described it, in an earlier blog post was like it, it’s coming in at like, series three, or like, season 3 million of a, of a show. A series like season 3 million of a show that was like, already complicated to begin with, because there’s just been evolution, evolution, evolution, evolution. And everything’s, you know, so, so intense and evolving so quickly. So the immune system is, you know, this super complicated, intricate defense system. Now, what does that have to do with elephants, mites? Well, if you think of a mouse, a mouse, his immune system is not designed to make the mouse live long. It’s pretty much just like anything that could throw it off course for that year or two, which is pretty much just going to be infections, that doesn’t care about cancer, because it’s probably not going to live long enough to get cancer, right? It’s really just like, cannot get infected for that year to like, and then so whatever happens, like anything that remotely looks like an infection, it’s going to blast it away. As a result, it’s going to cause a lot of collateral damage, right? Like imagine having Imagine if your police force not not to get political Madden, if your police force had this job that was like, you know, shoot anything that looks suspicious? Yeah, you would probably kill all the criminals, and you’d also kill a lot of other people. Which, again, not going to make any sort of political commentary about that. Now, um, meanwhile, if you think of an elephant and elephants immune system has job, first of all of like, it can’t be that aggressive, right, it can’t shoot anything that looks remotely threatening, because you’re going to kill a lot of things. And also, as the added problem of an elephant lives long enough to get cancer, and like cancer is much more complicated and much harder to deal with. And your immune system has to be a lot more clever to deal with it, because it is essentially your own body cells. Right. Um, so you know, essentially, in bigger species, the immune system through a, you know, preference of like, sort of like the adaptive immune system of neutrophils own parts of the immune system that are more selective, that tends to be preferred in bigger species, and in species that live longer. And in species that live less long, you tend to have more of like, for example, NK cells, which are sort of infamously aggressive. They’re called natural killer cells because they will, like, kill anything and that’s, that’s what they do and we have some amount in our body. But if you look at like a mouse proportionally, they have way more. So you know, they’re they have There’s so many NK cells that are on the lookout for literally anything that it doesn’t know, for a fact as benign, the NK cells will kill it.

Which is really interesting. If you take a look at like bats that’s lack NK cells. So that’s the live like 20 years. You know, if you think of a bad as a flying mouse, mouse lives one or two years about lives, 20 years, that’s totally like NK cells. So it’s, it’s a really interesting thing, and then you can start thinking about other ways. Okay, what does this mean for human longevity? And, you know, there’s stuff. There’s stuff relating to the immune system that we could go into for human longevity. But that’s, that’s another step. Anyways, long story short.

Will Jarvis 15:42
That’s super interesting. Yeah, we talked to before everything went down with Aubrey de Grey, we talked to him about opossums, and we get a lot of possums in North Carolina, there’s an island in North Carolina, off the coast where the possums live, you know, twice as long lived, like three years, instead of one year, one and a half years, on average. That’s because they have no natural predator. So it’s like, what kind of switch do they have? Right, where you can be kind of like that multiplied it has something to do with the immune system. It’s quite interesting. super interesting.

Trevor Klee 16:12
Yeah. I mean, you know, I, I don’t know much of opera degrees work. Specifically. I know, that crew tends to be really big on rapid Meissen, which is, you know, an immunosuppressant. Like caloric restriction, you know, has a lot of effects. But immunosuppression is, is one effect of caloric restriction. So there’s, there’s really interesting stuff going on there. You know, in terms of what the relation is, and ultimately, you know, how can we, you know, quote, unquote, hack it to extend our own longevity?

Will Jarvis 16:44
No doubt, no doubt. Are there any, you mentioned bat immune systems, is there anything unique about bat you mean system that lends them to create, you know, incubation of certain, you know, you know, viruses or anything like that, that are particularly pernicious to humans?

Trevor Klee 17:01
Excellent, excellent question. Um, you know, the quality of questions just, um, so, uh, yeah, that happens to be another thing that I have a long winded explanation about. Um, so bats are weird. So bats, we keep getting viruses from bats. And we get viruses from bats way more often than you would expect, right? Like, yes, people sometimes eat bats. Yes, they sort of live in our, like cities, but we get viruses from bats way more than we get viruses from, you know, rats, which are in much Claire’s context, all right, or pigs. Like a lot of things that we should be getting viruses more from, um, you know, Coronavirus is just one example. There’s, you know, a couple different viruses, which, you know, bats are natural reservoirs for. So it’s weird, right? Like, why bats? Um, and so one answer is bats have similar immune systems to us are similar enough. You know, it’s the similarity immune system depends on a lot of different things. Um, but you know, but pigs do have closer immune systems, Justin bats, fish have further immune systems. So it’s still not a great answer. So it starts getting to the point of what’s different about bats? And so the short answer is, what’s different about bats is that’s our dirty, dirty creatures, they are infected with viruses. They’re not just reservoirs for human viruses, they’re reservoir for all sorts of viruses. And it’s weird, because you’d expect them to all be dead. Like, why are they all dead? And so the, the answer seems to be that the reason why bats are all dead, is bats naturally, you know, they’re a flying mammal, which is a hard thing to do. It’s hard to fly. It’s really energy intensive. And that means that bats get their core temperature raised. And so what that means for bats is, first of all, they’re always kind of running a fever. So that’s, that’s going to help someone. Now the other thing that’s going on with bat, that’s different than, you know, other other mammals, is, as I mentioned before, bats have a weird immune system that probably has to relate to the fact that they’re always running a fever. And what happens when you’re always running a fever is you’re always sort of damaging cells. And you’re getting weird. Now, you have to understand that like, there’s only so many building blocks of things in your body and your body has recognizes enormous number of cells. And if it sees malformed cells or malformed DNA or malformed RNA, it’s usually going to kill it. Like that’s something that happens. You know, a lot in, you know, you get like necrosis from like a sunburn or something like that, you know, your body, your DNA gets damaged, and your body’s like, well, we got to kill this is it might be cancer, you know, kill it, get rid of it. Bats can’t afford to do that, because then they would just die. So their immune system has essentially adapted to be sort of on a constant state of low alert, where, you know, their immune system is active enough that they don’t die from these infections, but it’s not so active that it kills all the cells that are being damaged from their constant low grade fever. Gotcha. And what that means for bats is that bats, you know, are constantly a little sick. Gotcha, that’s constantly have the sniffles. Which works for them and doesn’t work for us. Because, you know, we come in contact with them. And it’s their, you know, we’re not like them, they have, you know, quote coronaviruses which to them or the sniffles, and das, you know, we get them and we end up dying.

Will Jarvis 21:08
So, it’s it is it’s something where, like, because you’ve got this constant kind of source of damage, there’s, is there more mutation of like Coronavirus or something like that. So there’s more novelty that could come from bat? Um, I mean, that may be an ignorant question. But,

Trevor Klee 21:24
um, so I mean, I don’t think coronaviruses need any, like, encouragement communicate, like, you know, they’re going to mutate, regardless, viruses mutate constantly. By recall correctly, the Coronavirus, especially, I think mutates a lot. I think it has poor air attacking. But the more important thing about bats is that they’re very, very social, they live in groups. Um, so it is like a natural testing pool. So anytime a virus has the chance to mutate, right? Like, if you think about, I sort of think about it as like capitalism, right? Like, you know, every virus is like selling something, right? And whoever manages to come up with a slightly better advertisement, or maybe a slightly better product, right? Like, it can spread across a million bats instantly. Um, so that’s, you know, there’s, there’s high evolutionary pressure in terms of, there’s lots of chances. Got it, like, you know, hit it big. That’s why, you know, to get to the Commerce example, why you see a lot more experimentation and sort of, like novel business ideas in New York City versus, you know, Wichita,

Will Jarvis 22:35
like, that’s super interesting, super interesting. sticking out the immune system, you know, people talk a lot about inflammation, but you know, you know, what is inflammation and why? Why does it matter for the immune system?

Trevor Klee 22:50
So this is a great question. This is one that I got an argument with people on Reddit about. So I started off, like, inflammation is something I think about a lot. Mainly because I don’t think there’s, I really dislike the way it’s usually thought about, like, a lot of stuff about, oh, we need to reduce inflammation. That’s like a very classic thing you’ll see. In medicine, you’ll see like, you know, people will say, oh, Advil is good, because it reduces inflammation, which is actually an interesting thing in the US people say, doctors will say, if you’re sick, take Advil, reduce inflammation. Yeah. in continental Europe, if you’re sick, they’ll they’ll say, Well, actually, inflammation is a good thing. Don’t reduce inflammation, don’t take Advil. So that was actually in the beginning of COVID. There’s a big argument of like, do you give COVID patients Advil? Were the Americans were like, of course, they have a fever, and the Europeans were like, No, don’t do it. Um, so yeah, this question of information, I think, is really interesting one, and part of the problem is, you know, we only have so many pathways in our body, right? And inflammation is really common pathway of if you get an infection, or if you get a pimple, or if you sprained your ankle, or, you know, whatever, you end up with this, like swollen red hot to the touch. Yeah. So it’s a super common pathway for a lot of things. It’s sort of like an initial alarm. So, you know, in terms of what’s the point of inflammation in the immune system, it’s, it’s tough. The answer has to be it’s important and it’s vital and it’s necessary. On the other hand, if you look at you know, the, some of the like, leading biologics, like the, just forgot the name, the one that’s it’s TNF alpha. It’s like the top selling biologic. I’m forgetting the name right now. But Like, you know, things that people take for arthritis or Crohn’s or whatever, can almost completely disable inflammation, and there doesn’t seem to be the crazy negative effects that you would expect. Interesting. Well, there’s something going on there. And that’s actually I mean, it’s a continual source of geonode. biologicals,

Will Jarvis 25:20
conceptually, but not well enough. Can you explain it to me?

Trevor Klee 25:24
Yeah, yeah, so biologic. Um, so basically, you know, there’s two main drug categories, you can app one is a drug that’s like you take from the outside world. And another is a drug that is designed to mimic something in the body, and very broad categories. And someone’s going to argue with me about that. So a biologic is meant to mimic something in the body. And like, the most common and the best selling ones, are monoclonal antibodies, you know, antibodies kill things. So we can make your body kill basically anything else in your body. So like, stuff, you know, autoimmune diseases, rheumatoid arthritis, we can have your body kill the things that would attack your joints. The other you know, a big selling category, of course, is insulin, which is a whole nother thing. But again, like we’re trying to mimic insulin, which is something your body naturally produces, or at least at least supposed to. So you know, a lot of these biologics do reduce inflammation incredibly well. And you do see some rise in cancer and some rising infection. So a healthy person definitely should not take these, but it’s still remarkable and maybe just as a result of like, the super high genic environments we live in, that like your Nana can take her, you know, weekly injection of Humira. That’s what it’s called. Yeah. For rheumatoid arthritis. And she doesn’t drop that of pneumonia. It’s it’s an interesting question for me and one that I’m not as well explored as I would want or expect.

Will Jarvis 27:04
Yeah. Well, that’s super interesting. Well, it’s like, going off of that. There’s this great debate in sports medicine, whether or not you should ice, you know, or provide heat like to, you know, you sprained your ankle. Like, it’s a great question, right?

Trevor Klee 27:19
Yeah, I, I’ve gone down that one myself. I do jujitsu pretty, pretty regularly, and I’m constantly injured. I’m in fact, I currently have a case of cauliflower ear from jujitsu. So questions of icing and resting and compression and elevation is one that I think about a lot. And honestly, I do nothing for my injuries. So I’m probably not the right person to ask about doing stuff from injuries.

Will Jarvis 27:47
Cervical, you know, building small biotech? What What have been the biggest challenges it? And and? And how is the FDA? You know, how is FDA? You know, how do you see it as a small biotech? Is it just completely horrifying? I’m assuming?

Trevor Klee 28:07
Yeah, yeah. So it, the thing about being small biotech is first of all, like, you know, and I’ve had a lot of, you know, I’ve had various businesses, some more successful than others have, like service business versus software business versus like, you know, sort of like a product business or info product business. And like, the thing about biotech is you can’t you can be small for only so long, right? So like, when we talk about small biotech, like, at the end of the day, you the smallest you’re going to be is, you know, a couple 100 people and like 30 million, or like $90 million in funding? Yeah, at least 100 million in funding. Like, there’s only so small you can be so very capital intensive. Yeah. Oh, geez. very capital intensive, very people intensive. You know, it’s so small biotech is, you know, we always got to be aware of what we’re talking about. Um, now, from the perspective of someone who have a company, though that’s not Pfizer, that’s not regeneron. It’s not, you know, Merck. You know, basically, what is the FDA, like, from the perspective of people who don’t know, people at the FDA? Which, that sort of, you know, when you submit to the FDA, does the person in charge reading like your submission, be like, Oh, hey, it’s those guys.

Unknown Speaker 29:44
Trevor? Yeah. Oh, hey, what’s up?

Trevor Klee 29:47
Yeah. And that’s, that’s sort of with any regulator. That’s a big advantage. Um, the FDA, I think, yeah. And granted, you know, I haven’t dealt with that many regulators. But the FDA, from my perspective is uniquely scary to deal with. If you don’t know, people there or, you know, at least like, you know, if you don’t have name recognition, and I think it’s there’s, there’s very little oversight of the FDA like, each so the FDA is divided up into divisions. Yeah. And the FDA has this like, very anti, they’re biased against approving things. And I mean that in the most literal sense of how they’re organized, they have steps of organization, and you have to make it past each step. So at any point, the people can say, like, you can submit it to the division and the division can say, No, they say, yes, it goes one level up. And those people can say no, or they can say yes, and then it goes one level up, and then they have to say yes, so you basically have to get three yeses to go. And only, you know, the nose can also generally Thank you. Um, so that’s, it’s a problem because there’s like, sort of, like unique, tiny fiefdoms. And like, you can really end up getting screwed. So so there’s a story recently of this biotech called axon. And they they’re doing for something for major depressive disorder, combination therapy, bupropion, dextromethorphan, which it’s not a brilliant combination, it’s like an antidepressant. And another thing that looks like a rapid antidepressant, but it seemed to have that effect in major depressive disorder. And they had sort of this terrible experience. Which, you know, I haven’t checked recently, I don’t even know if it’s resolved yet. Um, they were all set to launch, they hired all their people there, you know, ready to like, advertise, you’re good to go. And the FDA sends that this letter on July 20. And the letter basically just says, Wait, doesn’t say anything else. Just says we will let you know. Yeah, yeah. Which is like his brutal, right, like, you know, I’m so axon, you know, they don’t know what to do. They have to issue their publicly traded company, they have to issue a press release, saying the FDA told us to wait, we have no idea what they want us to wait for stock craters. Yeah, literally halves in a day, Jackson, three weeks later, the FDA sends them another letter. And all that letter says, or actually, they didn’t even send them a letter, they told him this in a phone call. They said we don’t need any additional information from them. They didn’t say stop waiting, they still want them to wait. They just said, you know, we don’t need any additional information. Would you can read us two ways. One is like them saying like, okay, at least we don’t have to, like do run another trial or something like that. Or you can think of it as like, Oh, I’m so screwed, the FDA doesn’t even care. They don’t even need any more information. They’re just, they’re ready to screw me. Ah, so it’s, it’s, you know, and that sort of thing happens. I don’t even know if that’s been resolved yet. Um, but you know, that’s just one case of a, it’s just, you know, one or two guys at the FDA. And they can just put a total halt to things and they don’t have to provide a reason. They don’t have to tell you why or why you’re waiting or anything. And they can just do it indefinitely. You can’t stop them. So it’s really tough, and like, you’re not, I think people misunderstand, like, what it’s like, like, you can’t sell anything, you can’t do anything. Right. Like, everything flows through that. Yeah. And like, you know, the FDA declares jurisdiction over pretty much everything. What’s on your website, is the jurisdiction of that. Yikes. marketing materials is the jurisdiction of the FDA. What goes on your factory is the jurisdiction of the FDA, every single part of your company is their jurisdiction, and any single part of it, they can tell you to change or that they don’t like it? Or, you know, they can just say like, you know, and they can sort of go for the nuclear option. They can say, you’re done, right, like you can be, then 100 million dollars in and the FDA can say no, you’re done. It’s it’s a tough business. Now, why is this the business I’m going into? Good question.

Will Jarvis 34:36
Do you think you can have a an outsize impact, I guess,

Trevor Klee 34:40
I mean, yeah, I mean, the, you know, I was I was being a little flippant, um, you know, in terms of things I like, things I enjoy. I really enjoy talking about this stuff, as you can probably tell, and you know, as some kind of utilitarian, in terms of sort of like the biggest impact on lives on happiness. Yeah, that’s it’s a big. You know, that’s, that’s a big reason why I’m doing it.

Will Jarvis 35:09
Yeah, though it is, it feels brutally underserved because of the regulatory hurdles, right, you know, people, it’s much, you know, software business enterprise SAS cost, like 100 grand in like, you know, to get up and running, and you could be selling after that. And that’s a big multiply versus 100 million, you know, what I mean?

Trevor Klee 35:30
I mean, it’s, it’s so different, but like, you know, in terms of, then, you know, you think about that, in terms of the effects on humans lives, you know, if I made another, like CRM, like, I don’t know, I mean, it might be nice, but like, it’s hard to be like, Oh, my God, like, you know, another CRM really

Will Jarvis 35:51
definitely driven humanity forward.

Trevor Klee 35:53
Yeah. You ever watch Silicon Valley, you know, making the world a better place? Yeah,

Will Jarvis 35:58
exactly. Exactly. super interesting. Do you have any advice for anyone, you know, working on a small biotech? You know, you’ve been on this journey? I mean, how long have you been on the journey? And? And is there any big advice that, you know, perhaps is non obvious that comes to mind?

Trevor Klee 36:13
There’s so much advice, in terms of how long I’ve been on the journey. So formally incorporated, incorporated in

early early this year, so it hasn’t been that long. I’ve been thinking about it for longer, and then you know,

what? Yeah, in terms of advice? Uh, so I want to go for like, very non obvious advice. Yeah. In terms of like, um, so in terms of my most non obvious advice for someone who’d be interested in this, it’s, I think animal studies don’t mean anything would be would be more interesting, interesting. I think the most common trap that people get caught in is they come up with these animal models. And they, like, do all these things to these animals. And then they like, test out their drug on the animals, and then they works on the animals, and then they’re like, all right, and then they’re surprised that no one takes them seriously, because generally, people speaking people don’t, unless you’ve done something really surprising. Um, and so my general advice is just, if you can just skip the animals, uh, I sort of, I wouldn’t say I got lucky I look for this on purpose, I found evidence in humans, before I picked my drug combination. I think there you can make a really clever in vitro model, if you have like, really good reasoning as to why but I think like, yeah, that’s sort of my biggest example, like, I’ll give you sort of the perfect example of this was, um, you know, for for the drug that I’m using right now, which is are sort of exploring right now. So cyclosporin is like the main ingredient. cyclosporin is immuno suppressant with neuroprotective properties. So it’s, it’s an interesting drug. And probably like a decade ago, maybe like two decades ago, people wasted like years and millions on it as a concussion drug. Really, that is because they had animal models. And animal model was essentially what it came down to it is you give a pig cyclosporin and then you hit it really hard. And then you’re like, what happens to the pig? You know, how’s he doing? Yeah, I’m, like, first of all,

Will Jarvis 38:49
she’s four pigs like Jesus Christ. Yeah. God. Yeah.

Trevor Klee 38:52
It’s just like, it’s an entire lab of people. Just

Will Jarvis 38:57
a hammer. That’s terrible.

Trevor Klee 38:59
Yeah, yeah. They’re like, you know, it’s an entire lab full of people just.

Unknown Speaker 39:04
Yikes. Yeah.

Trevor Klee 39:08
But like, the other problem is, you know, they were so proud of this model that, like, I’m sure they have this really complicated setup that they didn’t stop to think like, What relation to that have with humans? Yeah. Is or is it really doesn’t because the way humans get concussions is not, you can’t tell people to take a pill before you get a concussion? Because a concussion is not something you expect. Yeah. So you know, the way humans get concussions is we get a concussion. And then like three hours later, you know, someone’s like, Oh, I think you have a concussion. You should go to the doctor. Yeah. And so that’s what happens or you get in a car accident and the ambulance rushes you to the hospital, and you have a concussion and also like broken ribs and a bunch of other things wrong. Yeah. And so humans just don’t get concussions like that. And the trial failed because you can’t administer the drug like that.

Will Jarvis 40:00
So given it to the NFL running backs,

Trevor Klee 40:05
yeah, I mean, yeah, I mean that actually, you know, there’s a guy now and Boston who’s trying to like, who, who’s really trying to do a concussion pill? who’s trying actually to do this whole thing of like, what if we made these NFL players like take a pill every single time they got in the field, which I think is kind of not, I don’t think you can do that. Because the standard for giving drugs to healthy people is like, super high. And so if you have any side effects, they won’t let you do that. Um, but yeah, if I have any advice to small biotechs, especially like, you know, the majority of them aren’t going to be like me, I’m, it’s very, very rare. Like, my, my brother and I are like on a shortlist of people who’ve done this completely outside of any, like, cocoon of academia, or industry. Um, so most of these people are going to be in academia, I’d say, ditch the animal models, either convinced me with a really clever in vitro model, or, like, somehow got in human data, which I know is a difficult prospect, but like, figure it out.

Will Jarvis 41:16
That’s super smart. Well, I think that’s why it’s, it sounds like what you’re saying is people underrate how different animals are from humans, perhaps. Yeah, think about these things,

Trevor Klee 41:26
you come up with a really clever model, and you fall in love with it, and you’ve like, you get more interested in solving the map than the territory gotcha. Like, there’s this model of heart attacks, which essentially involves tying sutures around the aortic valve of a heart when people do this with mice. And I actually researched a bunch of these when I was interested in the topic. Um, and like, there’s paper after paper of how you suture the aortic valve of a mouse, which is really complicated, it’s really hard. You have to like performs very complex. And like, the problem is, you get so far down that rabbit hole, you don’t think like, you know, at the end of the day, this has nothing to do with a heart attack. Right? And no point in a heart attack. Does someone like no, you don’t get your balance? sutured? Um, so, uh, you know, I think people just fall in love with they’re very clever maps, and they forget about the territory, or they think the map is a lot easier to deal with than the territory. So then they only deal with the map. Yeah.

Will Jarvis 42:37
But that’s, that’s really well put I I do wonder, do you think you and your brother being kind of outside academia, which is where all life sciences happened, except for, you know, UT? I mean, literally, he’s probably UT. Right. But that’s the list. Do you think that gives you just a better, better incentive model, you know, to find things that are true? Because you’re not trying to optimize on publications, you’re trying to optimize on like, solving some kind of problem?

Trevor Klee 43:04
Um, I would say, I think, you know, and I have to give credit to him and his business partner, Josh, because, you know, they were doing this, you know, like, you know, back in 2013, and I’m just starting to do it now. Um, I think the, it really is a difference between what we optimize for, okay, I think we’re very concerned about like, how do you get this drug into patients, like, let’s get a drug that works on patients and get it into patients. And I think that’s something that he, when I put it that way, to me, it seems so obvious. And then like, these academic people will spend years messing around, and their research projects and like, they won’t even have a plan to get into patients, they’ll be like, 15 years into a research project, where they’re like, you know, the top line of their website is like, oh, curing Alzheimer’s or whatever. And they’ve spent like, 15 years, like messing around with, like, stupid research projects. Do you guys care about getting this in humans? Like what’s going on? Um, so yeah, I think it’s really a difference in like, what are you going for? Like, do you? Are you just aiming to, like, fund your science projects in perpetuity? Or do you actually want to cure people?

Will Jarvis 44:19
Right? And that’s almost like a weird thing to say, right? But it does seem to be very true.

Trevor Klee 44:25
Yeah. Oh, it’s a like, it’s insane to me the number of like, and you know, they they’re winning at some sort of game like, yeah, it’s insane to me, the number of them that get like $50 million, and can hire a whole crew. And then that’s it. That’s all they wanted to do. And they told their investors they wanted to cancer and they really just never cared. They just thought it was really neat to like, I don’t know genetically engineer viruses to do weird things, and they don’t their investors. It was cancer, but it’s actually just I don’t know, other stuff. yet. It’s fun project, you know,

Will Jarvis 45:06
very interesting. Very interesting. So I got one more line of questioning for you, you know, what’s the best learning environment for humans, anything, any actual stuff you found that you think people should apply?

Trevor Klee 45:20
Um, depends what you’re trying to learn. Um, I think the most important thing is, when I think about learning, I think of like, I always tell my students, there’s a loop and learning in the loop is you try something, you get it wrong, you realize that you got it wrong, and then you apply it to the like, yo, next similar thing. And I think that loop is for pretty much any skill is, is important. And I think how you change your environment, like, you need to structure your environment, so you can get things wrong, you know, when you got things wrong, and then you can apply it to the next thing. So like, which is hard to do. So I’ll give you an example. I learned French in high school, and my French is men. Um, I have a friend who’s a like language learners as a hobby. And at one point, he had like, seven or eight languages, he was actively learning Oh, wow. And he was incredible at them. And part of it was he did what you would expect and studied. And, you know, he would study grammar and study vocab, whatever. Um, but another part of it that he did that I never managed, is he failed constantly, he would go up to strangers and talk to them in their language. And, you know, he would do this in languages. He didn’t speak very well, like Russia, like he traveled around Eastern Europe, using Russian and like, I don’t his Russian at that point was worse than my French, I would not feel confident by going around like, you know, even France, nevermind, like, I don’t know, like, Francophone Africa, I guess would be an analogy, like trying just to get round in French with people who cannot speak English. He’s fine with that. He’s fearless. And like, you know, he starts off looking really dumb, because he makes really dumb language learning mistakes. But like, you know, he receives that constant feedback, and he iterates and the iterates. And by the end of it, I mean, I’ve seen it happen. He learns languages, much better than people who’ve been studying it for years, just because he fails constantly, and he’s constantly fixing it. Um, so I think that analogy of like, Okay, what am I doing? Like, I’m going to get things wrong, I’m going to fix it, I’m going to then apply it to the next person, action, whatever, I think is the ideal learning environment.

Will Jarvis 47:47
Gotcha. So so so some sense in that you need to get fast feedback. And you need to just keep keep iterating on things to really make good progress.

Trevor Klee 47:57
Exactly. You need to fail fast and iterate fast. So if you’re learning a language, you need to constantly be like looking like an idiot by using the wrong word. Right? If you’re learning jujitsu, because that’s something I think about a lot. Yeah, need to be trying a certain move a lot. And you need to figure out all the ways that move can go wrong. So you can finally like, come up with Okay, here’s how this move works in every situation that I want to use it in,

Will Jarvis 48:22
right? And it almost seems like if you’re not, you know, you can, if you’re not failing enough, you’re not pushing far enough. That makes sense. You’re not like getting out of like, you’re just doing the jujitsu moves, you know, like, he would never fail. But, you know, if you, if you’re not pushing over the edge a little bit, you’re not optimized enough.

Trevor Klee 48:42
So that’s, that’s one big issue. Another big issue is just people don’t recognize when they fail, and they just don’t even like, Yeah, and that’s sort of like a, you know, I think about Jiu Jitsu versus other martial arts, um, in jujitsu, you will know if you do a move wrong at some point, because at some point, you know, you we constantly do competitions. Yeah. And like, at some point, you’re going to get into competition, and you’re going to try that move. And someone’s just gonna, like, smack your face into the mat. And it’s like, oh, this move does not work. Um, if you do, like, I don’t know, like, traditional Kung Fu, and you never spar, you will never know you did it wrong. because no one’s ever gonna, like, you know, no one’s ever gonna smack you. Right? Like, like, think your entire life. Oh, I have this really sweet move. And like, you know, you’re, I guess one day you probably never figured out one day you’re gonna get this free fight. You’re gonna try it and then like, it’s just gonna be some idiots gonna clock you. But yeah.

Will Jarvis 49:43
No doubt that. It’s great. I love that analogy. Um, one more big question. You know, how can we teach calculus in a more robust way? And are there any, any lessons we can learn from that apply elsewhere?

Trevor Klee 50:00
calculus, my greatest weakness? Um, yeah. So in terms of calculus, um, I think, you know, I, this was something I was thinking about, like, I have lots of problems with how I was taught in school, which I guess maybe I don’t know if that drives my interest in education during my education, or vice versa. Like, you know, I started getting really interested in teaching and then I was like, wait, shit, why is why was my teaching in school, so shit. So, I think for calculus, and for biology and for lots of things, um, I think the biggest problem we have when we teach kids is that they never love it. And they never learned to love it. And the reason they never learned to love it as they never find it. They never find it surprising or interesting. So like I said, I always have my biology essays with, that’s weird. You can start a calculus course the same thing. The same way. I mean, you know, the way calculus was originally discovered, a lot of it was like, you know, these European, you know, mathematician, slash scientists, you know, natural philosophers, as they call themselves were obsessed with astronomy, and they kept seeing weird things with astronomy. And they come up with, you know, that’s why you had like, you know, simultaneous physics and calculus at the same time, because, like, a big part of it was just, you know, they were constantly looking at the night slide, that was something they really cared about. And like, you know, they were constantly thinking, like, How do I explain this? This is weird. How do I explain this? How do I model this? How do I predict this? Um, and I think starting with that, and then being like, this is why anyone would give a shit is very important. And I think instead, in calculus, or in many other things, you know, we learn it as like, here’s like, God’s given truth that you have to learn. Like, it’s, you know, the Bible, right? And you don’t get to learn, like you learn calculus. And then, if you’re an engineering college, four years later, you get to learn why anyone would care about, which is crazy. You know, there’s an old essay that I love, which was like, What if we taught Music The same way we taught math, which was no kid ever gets to hear a song or like, an instrument until they learn the scales and they learn how to read notes. Right? It’d be terrible. you’d hate music. You will never ever have a musician. Like Yeah, but that’s that’s how we teach calculus. So

Will Jarvis 52:34
that out, really well put. Well, Trevor, thank you so much for coming on. And taking the time tonight. Where can people find your work? Where should we send people? Uh,

Trevor Klee 52:44
so depends what you want from me. But easiest way is just Trevor CLI comm Tru VR, KL e Comm. I’ve got links out to my other stuff. If you want to check out my really bare bones, biotech company websites, highway farm calm, that’s pH ar n.com. And then otherwise, just Google me. I’m like super gullible, as long as you spell my last name, right. KL E. You will, you will find me.

Will Jarvis 53:13
That’s great. That’s good gift. Awesome. Well, thanks, Trevor. Really appreciate it.

Trevor Klee 53:17
All right. My pleasure. Thank you.

Will Jarvis 53:24
Thanks for listening. We’ll be back next week with a new episode of narratives.

Transcribed by https://otter.ai

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