WEBVTT - Making a Universal Flu Vaccine 0:00:15.356 --> 0:00:26.956 Pushkin. I love vaccines, I really do. Vaccines train your 0:00:26.996 --> 0:00:32.316 body to make these antibodies that protect you against deadly diseases. 0:00:33.196 --> 0:00:35.516 It's a thing you get so you don't get sick 0:00:35.596 --> 0:00:38.396 in the first place, and it's so clever and so 0:00:38.636 --> 0:00:42.996 elegant and so obviously useful. I think it is honestly 0:00:43.036 --> 0:00:45.756 fair to say that vaccines are truly one of the 0:00:45.916 --> 0:00:49.236 greatest inventions of all time, on the very short list. 0:00:49.236 --> 0:00:52.356 They've saved hundreds of millions of lives. Give me all 0:00:52.396 --> 0:00:57.156 of them, Give me all of the vaccines. But I 0:00:57.196 --> 0:01:03.276 gotta say the flu vaccine sucks. The flu vaccine sucks. 0:01:03.356 --> 0:01:08.196 It really does, And for a somewhat simple reason. The 0:01:08.276 --> 0:01:12.476 flu virus mutates so quickly that we can't come up 0:01:12.516 --> 0:01:15.596 with vaccines fast enough to keep up with it. So 0:01:16.036 --> 0:01:19.596 every year scientists develop a new vaccine, but even in 0:01:19.636 --> 0:01:23.236 the time it takes to manufacture that vaccine, the virus 0:01:23.316 --> 0:01:26.436 keeps mutating. As a result, even if you get a 0:01:26.436 --> 0:01:29.156 flu shot every year, there's still a good chance that 0:01:29.196 --> 0:01:31.956 you'll get a bad case of the flu. Last year's 0:01:31.996 --> 0:01:35.676 flu shot, for example, was only about thirty five percent effective, 0:01:36.676 --> 0:01:39.876 And so for decades now, scientists have asked a fairly 0:01:39.916 --> 0:01:43.076 obvious question, is there some way to come up with 0:01:43.116 --> 0:01:45.836 a flu vaccine that would work not just for the 0:01:45.876 --> 0:01:48.796 strain of flu that is circulating right now, but for 0:01:48.916 --> 0:01:52.556 almost all strains of flu, including strains that haven't even 0:01:52.676 --> 0:02:01.556 evolved yet. I'm Jacob Goldstein and this is What's Your Problem, 0:02:01.596 --> 0:02:03.516 the show where I talk to people who are trying 0:02:03.556 --> 0:02:07.916 to make technological progress. My guest today is Jacob Glanville. 0:02:08.036 --> 0:02:11.956 He's a bioengineer and an immunologist, and he's the founder 0:02:11.996 --> 0:02:15.396 and CEO of Centivax, a company that's trying to make 0:02:15.596 --> 0:02:19.916 a universal flu vaccine, a flu vaccine that will consistently 0:02:20.036 --> 0:02:23.076 and reliably prevent people from getting the flu. 0:02:23.396 --> 0:02:26.916 You imagine talking to a generation that didn't have flu anymore. 0:02:26.956 --> 0:02:27.996 They would think we were nuts. 0:02:28.036 --> 0:02:29.676 They were just like, oh, yeah, every year we have 0:02:29.716 --> 0:02:32.636 a circulating pandemic and then six months later there's another one, 0:02:32.636 --> 0:02:34.596 and yeah, you know, fifty thousand people die. 0:02:34.676 --> 0:02:37.396 But what do you do? And like, that's nuts, But 0:02:37.916 --> 0:02:38.876 we take it for granted. 0:02:40.076 --> 0:02:43.556 The vaccine that Jacob's company, Centivax, is developing for flu, 0:02:43.876 --> 0:02:47.596 is likely to go into human trials next year. The 0:02:47.596 --> 0:02:51.676 company is also in earlier stages of developing universal vaccines 0:02:51.716 --> 0:02:56.996 for HIV and COVID, among other diseases, and wildcard. They 0:02:56.996 --> 0:03:00.876 have also worked on creating a broadly effective anti venom 0:03:01.116 --> 0:03:04.036 for snake bites. We talk about snake bites later in 0:03:04.076 --> 0:03:08.076 the conversation. To start, Jacob told me about the moment 0:03:08.116 --> 0:03:11.756 he first got the ia for a universal vaccine. It 0:03:11.836 --> 0:03:14.836 was around twenty twelve. He was working for the drug 0:03:14.836 --> 0:03:18.356 company Feizer, and he wasn't working on vaccines, but he 0:03:18.516 --> 0:03:22.996 was doing something related. His job was to identify antibodies 0:03:23.036 --> 0:03:25.796 that could be used to treat disease, and at this 0:03:25.876 --> 0:03:29.156 particular moment, he was studying antibodies that would bind to 0:03:29.236 --> 0:03:33.076 a particular protein called PCSK nine. 0:03:33.516 --> 0:03:35.876 And so I was riding back on my motorcycle one 0:03:35.916 --> 0:03:38.996 evening and I was reflecting on this problem where there 0:03:39.036 --> 0:03:41.916 was this target called PCSK nine. It kind of looks 0:03:41.956 --> 0:03:47.076 like Mickey mouse's head, and they really wanted antibodies against 0:03:47.196 --> 0:03:49.556 kind of where the neck is that if you get 0:03:49.556 --> 0:03:50.556 an anybody there. 0:03:50.476 --> 0:03:53.596 Then that can affect cholesterol and lower cholesterol. 0:03:54.156 --> 0:03:56.436 The problem is that they're getting anybodies against the ears, 0:03:57.316 --> 0:03:58.756 and they weren't getting anybodies. 0:03:58.396 --> 0:03:58.996 Against the neck. 0:03:59.236 --> 0:04:00.516 And so I was trying to figure out, is there 0:04:00.516 --> 0:04:03.196 an engineering way to sort of focus the immune system 0:04:03.356 --> 0:04:06.436 at arbitrary sites that would save me a bunch of time. 0:04:06.756 --> 0:04:09.636 And I started imagining, what if I were to take 0:04:10.356 --> 0:04:13.556 that target not just from humans, but from like a 0:04:13.596 --> 0:04:18.276 donkey and an alligator and a chicken, and like just 0:04:18.716 --> 0:04:21.956 take a swath of different versions of that. They were 0:04:21.956 --> 0:04:24.196 different just about everywhere up in the ears, but they 0:04:24.196 --> 0:04:25.916 were the same down where the neck was. 0:04:26.196 --> 0:04:26.436 Huh. 0:04:26.796 --> 0:04:27.476 And then if I. 0:04:27.516 --> 0:04:30.556 Mixed those together and diluted each one so there wasn't 0:04:30.676 --> 0:04:33.436 enough of any one of the species of PCSK nine, 0:04:33.636 --> 0:04:35.996 then maybe only the neck would be the thing which 0:04:36.076 --> 0:04:37.956 was shared across all of them, and the entire immune 0:04:37.956 --> 0:04:39.356 system would focus on uh huh. 0:04:39.396 --> 0:04:41.756 So like in total, the sort of sum total of 0:04:42.556 --> 0:04:44.316 the mix, it would be like a lot of neck. 0:04:44.476 --> 0:04:46.956 The neck is conserved. The neck is what is the same, 0:04:47.516 --> 0:04:51.556 and there's only enough of that to induce the antibody response. 0:04:51.756 --> 0:04:54.356 So that then if you whatever inject that into an 0:04:54.436 --> 0:04:56.916 animal or a person, what the person's immune system is 0:04:56.956 --> 0:04:58.476 going to see is a lot of neck. 0:04:58.676 --> 0:05:00.636 Yeah, And so they finally focus on the neck instead 0:05:00.636 --> 0:05:02.956 of getting distracted by the ears. That was the principle, 0:05:03.716 --> 0:05:05.436 And so I got home, and then at a certain 0:05:05.436 --> 0:05:07.956 point I realized I was being an idiot and what 0:05:08.316 --> 0:05:10.116 this was was not a way to save a few 0:05:10.116 --> 0:05:13.876 months on an Anybody discovery campaign, that this was a 0:05:13.876 --> 0:05:16.236 potential window opening to the to the. 0:05:16.196 --> 0:05:17.596 Holy grail of vaccine science. 0:05:17.836 --> 0:05:21.076 The holy grail is that all of the major viruses 0:05:21.076 --> 0:05:26.836 that we're confronted with flu, influenza, HIV, ebola, these viruses 0:05:26.916 --> 0:05:30.956 mutate and change, but they always have some little spot 0:05:31.036 --> 0:05:34.316 that they cannot mutate. And those spots are always super important. 0:05:34.316 --> 0:05:36.596 That's why they can't mutate it because if you mutate it, 0:05:36.596 --> 0:05:37.276 the virus. 0:05:37.036 --> 0:05:38.036 Is no longer infectious. 0:05:38.116 --> 0:05:41.396 Yeah, And normally they get away with it by having 0:05:41.596 --> 0:05:44.676 distracting areas and most of the surface that can mutate. 0:05:44.796 --> 0:05:46.916 And that's why we have to update our flu shots 0:05:46.916 --> 0:05:47.356 every year. 0:05:47.716 --> 0:05:50.916 Distracting meaning distracting to our immune systems, like our more 0:05:50.916 --> 0:05:53.836 immune systems. Ooh, I like the ears. I like that 0:05:53.876 --> 0:05:57.036 shiny part on top, and that's exactly Yeah. 0:05:57.076 --> 0:06:00.076 Basically, the conserved Achilles heel is a small site and 0:06:00.116 --> 0:06:02.156 most of the surface can vary, and it can't it 0:06:02.196 --> 0:06:04.756 gets away with not changing the critical site by varying 0:06:04.796 --> 0:06:07.116 lots of stuff around it and taking advantage of the 0:06:07.156 --> 0:06:09.476 fact that the immune system doesn't know the difference, and 0:06:09.516 --> 0:06:12.756 so to the ability to focus the immune system against 0:06:12.756 --> 0:06:16.476 a conserve site would be the basis of a universal vaccine, 0:06:16.556 --> 0:06:19.876 because instead of targeting one strain of flu or one 0:06:19.916 --> 0:06:23.476 strain of coronavirus or one strain of HIV, you could 0:06:23.556 --> 0:06:25.916 target the shared sites that the virus is never allowed 0:06:25.956 --> 0:06:28.076 to mutate. And if you do that, then you're suddenly 0:06:28.156 --> 0:06:31.276 hitting the entire class of influenza viruses, including future ones 0:06:31.276 --> 0:06:32.156 that haven't evolved yet. 0:06:32.236 --> 0:06:32.356 Right. 0:06:32.756 --> 0:06:34.876 I mean that part of the idea is the part 0:06:34.916 --> 0:06:38.876 everybody knew already, right, Like that is the relatively obvious idea. 0:06:38.876 --> 0:06:41.036 It's like, don't go for the part that changes, go 0:06:41.196 --> 0:06:43.276 for the part that's the same. Right. The hard thing 0:06:43.876 --> 0:06:47.876 is how do you do that? So had when you 0:06:47.956 --> 0:06:50.636 described the idea of like, oh, just take a bunch 0:06:50.636 --> 0:06:55.116 of different ones, dilute them, mix them together. Nobody had 0:06:55.196 --> 0:06:56.076 thought of that before. 0:06:56.796 --> 0:07:01.476 Yeah, so surprisingly not to your point, people since the 0:07:01.556 --> 0:07:04.756 nineties were aware of these conserve sites, and so they 0:07:04.836 --> 0:07:05.836 knew where the sites were. 0:07:05.916 --> 0:07:08.156 We had crystal structures it was just, how the hell 0:07:08.196 --> 0:07:10.036 do you get the immune system focus on those sites? 0:07:10.116 --> 0:07:12.436 Was the problem. Yeah, and people have tried a couple 0:07:12.436 --> 0:07:12.916 different things. 0:07:12.956 --> 0:07:15.676 They tried chopping out parts of the protein, but then 0:07:15.716 --> 0:07:18.036 the site you're interested in falls apart. It's like trying 0:07:18.036 --> 0:07:21.476 to grab a snowflake. It'll melt in your hands. They 0:07:21.516 --> 0:07:23.956 tried a couple other techniques that didn't work out. 0:07:24.756 --> 0:07:26.956 So okay, so you have this new idea for how 0:07:26.996 --> 0:07:30.396 to make a universal vaccine that nobody's tried before, which 0:07:30.516 --> 0:07:33.156 to use flu for an example, would mean you take 0:07:33.196 --> 0:07:36.076 a bunch of different strains of flu, and in particular 0:07:36.116 --> 0:07:38.996 the sort of spike protein of the flu that your 0:07:39.196 --> 0:07:42.796 immune system sees. Then you dilute them and mix them 0:07:42.836 --> 0:07:46.036 all together in a single vaccine. So what the patient's 0:07:46.036 --> 0:07:48.436 immune system winds up seeing the most of is the 0:07:48.476 --> 0:07:52.196 part that's the same in all those different strains, the 0:07:52.236 --> 0:07:55.396 part that doesn't change. And then ideally the patient will 0:07:55.436 --> 0:07:59.716 develop antibodies to that part, the part that doesn't change, 0:08:00.116 --> 0:08:02.716 and therefore the patient will be immune to like almost 0:08:02.796 --> 0:08:03.676 any strain of flu. 0:08:04.076 --> 0:08:06.196 Yeah, and you recognize it might not work right. 0:08:06.276 --> 0:08:08.236 You always are like, look, this is a pipe drain, 0:08:08.276 --> 0:08:09.916 but like I could not go to sleep because I 0:08:09.956 --> 0:08:11.796 was like, if this works, this is such a stunning 0:08:11.796 --> 0:08:14.756 breakthrough that it's like it's hard to sleep when you're 0:08:14.796 --> 0:08:15.396 thinking about that. 0:08:15.476 --> 0:08:16.916 It sort of becomes all consuming. 0:08:17.756 --> 0:08:21.316 So you get this idea, and you're working for Pfeiser, 0:08:22.316 --> 0:08:26.396 a company that makes vaccines. By the way, what do 0:08:26.436 --> 0:08:26.756 you do? 0:08:27.756 --> 0:08:27.956 Yeah? 0:08:27.996 --> 0:08:31.436 So again, I was not doing anything involving their vaccine group. 0:08:31.436 --> 0:08:33.556 I was doing for intellectual property reason. 0:08:33.636 --> 0:08:36.476 Ye. Yes, I was not working on vaccines at Pfizer. 0:08:38.876 --> 0:08:41.076 I resigned. So I did two things. 0:08:41.116 --> 0:08:45.236 I started my first company, Distributed Bio, and I also 0:08:45.276 --> 0:08:48.436 applied for the PhD program in immunology at Stanford. 0:08:48.516 --> 0:08:50.516 And you do this because of your idea? 0:08:51.076 --> 0:08:51.356 Yeah? 0:08:51.516 --> 0:08:55.876 Yeah, Because basically I applied to the PhD program because 0:08:55.876 --> 0:08:58.716 I was like, if I'm wrong, I need to stop 0:08:58.716 --> 0:09:01.396 thinking about this. I need to surround myself with brilliant 0:09:01.396 --> 0:09:03.996 immunologists who can kick holes in this, and I need 0:09:04.036 --> 0:09:06.316 to be able to make sure I'm not being myopic. 0:09:06.476 --> 0:09:09.956 And then if I'm right, I need the world to 0:09:09.956 --> 0:09:10.276 hear me. 0:09:10.396 --> 0:09:12.516 And so I need to be a card carrying PhD 0:09:12.556 --> 0:09:15.236 immunologists from Stanford so that people go, Okay, this guy 0:09:15.316 --> 0:09:19.716 is into some Yahoo and then for the company side, 0:09:19.996 --> 0:09:21.956 I just saw this opportunity to be able to go 0:09:22.036 --> 0:09:24.076 test it because I originally I did go out and 0:09:24.116 --> 0:09:26.796 I try to talk to some vcs in twenty twelve, 0:09:27.556 --> 0:09:29.556 and I think there, you know, predictably, their answer is like, 0:09:29.556 --> 0:09:30.156 what the hell is this? 0:09:30.236 --> 0:09:31.036 And who the hell are you? 0:09:31.116 --> 0:09:34.396 And you were a bachelor's degree, right, we'd worked at 0:09:34.636 --> 0:09:37.556 Miser for a couple of years, like a million other people, 0:09:37.676 --> 0:09:38.476 so not you. 0:09:38.476 --> 0:09:40.196 Know, you can't blame him. I was like, I guess 0:09:40.236 --> 0:09:41.836 I'm nobody right now. Let me go fix that. 0:09:41.996 --> 0:09:45.716 Yeah, And so I decided that I was going to 0:09:45.796 --> 0:09:48.956 go found a company because there was some work I 0:09:49.036 --> 0:09:51.996 was doing at Pfeiser that i'd public created some publications 0:09:52.036 --> 0:09:54.076 on using the deep genomic sequencers to look at the 0:09:54.076 --> 0:09:57.476 immune system and then building better anybody libraries with what 0:09:57.476 --> 0:09:59.796 we learned about that, and I realized there was a 0:09:59.796 --> 0:10:01.956 business that could be built on that. And my intention 0:10:02.116 --> 0:10:04.276 was to build that business and use it to subsidize 0:10:04.276 --> 0:10:07.676 some of the early proof deep risking experiments. 0:10:07.156 --> 0:10:09.916 On this universal vaccine concept. And so that's what I did. 0:10:09.956 --> 0:10:12.516 So I just did both for five years and didn't 0:10:12.516 --> 0:10:15.716 sleep that much until the PhD. Graduated from that, and 0:10:15.716 --> 0:10:17.956 then later I sold the first company distributed by it. 0:10:18.076 --> 0:10:20.796 So the company you start you're selling your clients are 0:10:20.876 --> 0:10:24.796 drug companies essentially, right, But you're doing that that's sort 0:10:24.836 --> 0:10:28.556 of your side hustle. That's sort of funding your vaccine dream. Right. 0:10:29.116 --> 0:10:34.556 And while you're doing that, you start doing this research 0:10:34.956 --> 0:10:39.236 on your vaccine in pigs in Guatemala, right, tell me 0:10:39.276 --> 0:10:39.756 about that. 0:10:40.876 --> 0:10:43.596 The background is I grew up in Guatemala. My parents 0:10:43.596 --> 0:10:46.876 are Americans, but they met in Guatemala in the seventies 0:10:46.916 --> 0:10:49.516 and they built this hotel and restaurant with my grandmother. 0:10:50.316 --> 0:10:51.276 Hippie dream. 0:10:51.876 --> 0:10:53.676 Yeah, the hippie dream, that's exactly what it is. 0:10:53.676 --> 0:10:57.156 There's small hippie enclaves down there, and then there's most 0:10:57.156 --> 0:10:59.276 of the village is the wheel may In and then 0:10:59.316 --> 0:11:01.796 there's Katchi Kels and some other Mayan communities, and it's 0:11:01.876 --> 0:11:04.436 very beautiful lake. So it makes sense that the hippies 0:11:04.436 --> 0:11:04.916 would go there. 0:11:05.556 --> 0:11:07.036 The Civil War largely. 0:11:06.796 --> 0:11:09.276 Drove them away, but my family, when I was a 0:11:09.276 --> 0:11:11.076 little boy, they went down there to try to fix 0:11:11.156 --> 0:11:13.196 up and sell the property. And then one thing led 0:11:13.196 --> 0:11:15.556 to another and we ended up becoming innkeepers. 0:11:14.996 --> 0:11:18.356 And so I grew up in the village. 0:11:19.876 --> 0:11:21.716 I think it probably had an effect on my interest 0:11:21.756 --> 0:11:24.316 in immunology in the first place. And I had this 0:11:24.316 --> 0:11:27.196 connection to Guatemala, and I ended up maintaining a connection 0:11:27.316 --> 0:11:29.996 to USAK, which is the University of San Carlos, the 0:11:30.476 --> 0:11:34.636 National University. And so fast forward in my career too, 0:11:34.676 --> 0:11:38.236 when I was thinking about universal vaccines, like one of 0:11:38.236 --> 0:11:41.076 my I say, one of my deep impressions left from 0:11:41.076 --> 0:11:43.556 some work adviser was this. I was very impressed with 0:11:43.556 --> 0:11:46.676 a group that was doing animal health work because I 0:11:46.716 --> 0:11:49.436 felt like, instead of using mice, they would often ask 0:11:49.476 --> 0:11:52.396 what's the most relevant and similar animal model to humans 0:11:52.436 --> 0:11:55.516 for this indication? Mouse is not a person like no 0:11:55.636 --> 0:11:57.596 animal as a person, but you can find something that's 0:11:57.636 --> 0:12:01.556 a closer fit and waste less time on failed translation. 0:12:02.556 --> 0:12:04.916 And so I liked I had this technology. I was 0:12:04.916 --> 0:12:06.956 trying to figure out where to apply it. I actually 0:12:06.956 --> 0:12:08.556 called one of the guys and I was like, what's 0:12:08.596 --> 0:12:13.196 the venor market that has a rapidly mutating pathogen that's 0:12:13.196 --> 0:12:14.196 also found in humans? 0:12:15.116 --> 0:12:17.396 And he said, it's definitely flu in pigs. 0:12:17.476 --> 0:12:19.916 They get the flu in fact they transmitted to humans, 0:12:20.316 --> 0:12:23.156 and so pigs are definitely not as convenient as mice, 0:12:23.196 --> 0:12:24.756 but I felt that the data would be much more 0:12:24.796 --> 0:12:26.676 meaningful because they actually get the flu. 0:12:26.796 --> 0:12:27.036 Yeah. 0:12:27.636 --> 0:12:30.436 So I ended up doing it back in Guatemala with 0:12:30.956 --> 0:12:34.436 Airwin Calagua, my collaborator at the University of San Carlos, 0:12:35.036 --> 0:12:36.996 and some property that my father had. So I ended 0:12:37.036 --> 0:12:38.916 up making some calls. I found out we could get 0:12:38.916 --> 0:12:41.156 the pigs. There was a vet who was involved in 0:12:41.196 --> 0:12:44.156 the H one in one two thousand and nine pandemic 0:12:44.156 --> 0:12:45.116 shift monitoring. 0:12:45.436 --> 0:12:48.836 You're doing it in Guatemala because it's cheaper. Basically you're offshoring. 0:12:48.916 --> 0:12:52.316 You're yeah, it's way cheaper, radically cheaper and faster. I 0:12:52.316 --> 0:12:55.276 think if the cycle time is astonishingly slow to do 0:12:55.396 --> 0:12:57.756 animal studies and ask for grants like you're lucky to 0:12:57.796 --> 0:12:59.436 get a study done like once every two and a 0:12:59.476 --> 0:13:03.076 half years according to the US model, Whereas in Guatemala 0:13:03.236 --> 0:13:05.556 the costs were radically cheaper. I could build a facility 0:13:05.596 --> 0:13:07.836 to spec and I was, you know, I'm an engineer, 0:13:07.876 --> 0:13:09.916 so I need to be able to do cycle yeah. Yeah, 0:13:09.956 --> 0:13:12.596 and so this enabled me. I think we ran five studies. 0:13:12.276 --> 0:13:13.796 There over a couple of year period. 0:13:13.836 --> 0:13:15.996 We're able to go pretty quickly go in and do 0:13:16.196 --> 0:13:19.796 rapidly de risk this universal vaccine technology in a way 0:13:19.796 --> 0:13:23.356 that was economically feasible given the growing profits but still 0:13:23.396 --> 0:13:26.476 finite profits that I had from the Anybody discovery and 0:13:26.556 --> 0:13:27.716 software side of the business. 0:13:27.996 --> 0:13:30.276 So when you're doing those pig studies, I mean just 0:13:30.316 --> 0:13:34.436 to return to your initial idea of using essentially different 0:13:34.476 --> 0:13:38.276 different strains. Let's say you got to figure out what's 0:13:38.316 --> 0:13:41.556 the right concentration, because if you do too little, it's 0:13:41.836 --> 0:13:44.676 you don't get any meaningful immune response, and if you 0:13:44.716 --> 0:13:46.756 do too much, then you're getting immune response to the 0:13:46.756 --> 0:13:48.636 parts that are not conserved, to the parts that you 0:13:48.676 --> 0:13:50.796 don't want immune response to exactly. 0:13:50.836 --> 0:13:52.796 I was just just proving the concept right because I 0:13:52.796 --> 0:13:54.636 think there's definitely people who are like, this isn't going 0:13:54.716 --> 0:13:54.956 to work. 0:13:54.996 --> 0:13:55.596 There's no way. 0:13:56.516 --> 0:13:59.316 And look, if I'm wrong, then if it doesn't matter 0:13:59.356 --> 0:14:01.516 if I put fifteen things in, if each one's below 0:14:01.516 --> 0:14:04.316 the dose and they're not interacting like I was hypothesizing, 0:14:04.436 --> 0:14:06.676 then you should see no immune response. 0:14:06.756 --> 0:14:08.196 Right, So I could have just been wrong. That's the 0:14:08.236 --> 0:14:10.596 other thing I was testing, does the principle hold? And 0:14:10.796 --> 0:14:12.356 the answer was definitively yes. 0:14:13.036 --> 0:14:14.996 So okay, So you have this idea that it works 0:14:16.236 --> 0:14:18.996 somewhere around here, you sell I don't know which one 0:14:18.996 --> 0:14:20.796 is the side hustle and which one is the main hustle. 0:14:20.836 --> 0:14:24.276 I guess vaccinating pigs in Guatemala sounds like a side hustle, 0:14:24.316 --> 0:14:26.396 even though it's the thing you really care about. Right, 0:14:28.236 --> 0:14:32.396 you sell distributed bio and you've spin out sent to 0:14:32.476 --> 0:14:37.956 vax the vaccine company, right, and then what then where 0:14:37.996 --> 0:14:38.236 are you? 0:14:38.796 --> 0:14:41.596 Yeah? So it was a good time. 0:14:41.676 --> 0:14:46.196 So we got the Gates Foundation awarded us this in 0:14:46.236 --> 0:14:49.196 the Pandemic Threatgrand Challenge award to test the vaccine no 0:14:49.236 --> 0:14:52.636 longer in Guatemala, but up in American facilities that had 0:14:52.756 --> 0:14:56.516 biosafety containment, so that we could challenge the animals who've 0:14:56.556 --> 0:15:00.196 been vaccinated with these strains that had evolved after the mixture. 0:15:00.276 --> 0:15:03.036 So we deliberately pretended it was two thousand and seven 0:15:03.436 --> 0:15:05.516 and only included strains up to two thousand and seven. 0:15:06.036 --> 0:15:08.156 Then we challenged the animals with the two thousand and 0:15:08.196 --> 0:15:11.756 nine pandemic shift virus, a twenty twelve a twenty seventeen virus. 0:15:12.036 --> 0:15:15.036 That's a big question, right, It's like testing something that's 0:15:15.036 --> 0:15:18.276 out of the model, right, Like it's saying, Okay, we 0:15:18.356 --> 0:15:21.276 give somebody this vaccine and then there's a new kind 0:15:21.276 --> 0:15:24.796 of flu. Does it work? Yeah? Yeah, And it. 0:15:24.836 --> 0:15:25.836 Felt that that was essential. 0:15:26.076 --> 0:15:28.036 By the way, those same pigs we pulled their serum 0:15:28.076 --> 0:15:30.036 out of the freezer over the last couple of months 0:15:30.076 --> 0:15:32.396 and they neutralized the H five and one that's currently 0:15:32.436 --> 0:15:34.916 outbreaking in cows and chickens and some people. 0:15:34.956 --> 0:15:37.596 Huh the bird flu. 0:15:36.236 --> 0:15:38.556 The great super broad immune response. 0:15:39.596 --> 0:15:43.476 So the timing was good. CR wanted to buy. I 0:15:43.516 --> 0:15:47.836 was happy to do it, and my condition was I'm like, look, 0:15:47.876 --> 0:15:50.676 I want to take this universal vaccine technology with me 0:15:50.756 --> 0:15:52.476 to a new company, and they agreed to that. That 0:15:52.636 --> 0:15:56.116 was December thirty first, twenty twenty is when when the 0:15:56.316 --> 0:15:59.636 sale completed, and so basically January first. 0:15:59.636 --> 0:16:02.036 That is a remarkable time to go all in on 0:16:02.076 --> 0:16:05.676 a universal vaccine. December thirty first, twenty twenty. 0:16:06.036 --> 0:16:09.996 We transitioned over January first, twenty twenty one. I'm now 0:16:10.036 --> 0:16:12.916 the CEO and founder of Cinevacs, and I started calling 0:16:12.996 --> 0:16:15.036 an army of geniuses of the best people that I've 0:16:15.076 --> 0:16:17.156 worked with to gather together, and I was like, look, 0:16:17.196 --> 0:16:18.436 this is going to be the big one. 0:16:18.316 --> 0:16:21.276 Where like a like a heist movie, like, oh it's eleven. 0:16:22.276 --> 0:16:24.436 Yeah, it was like the best people of my entire 0:16:24.476 --> 0:16:25.236 career I worked with. 0:16:25.356 --> 0:16:26.996 You don't need a lot, you just need every person 0:16:26.996 --> 0:16:29.196 to be exceptional, and like, if we do our jobs right, 0:16:29.236 --> 0:16:30.516 we touched the long arch of history. 0:16:30.676 --> 0:16:35.316 Yeah, so what have you figured out? Like, what have 0:16:35.356 --> 0:16:38.156 been the key things you've figured out? Since then? 0:16:38.436 --> 0:16:42.876 We identified a couple extra people we brought in, including 0:16:42.996 --> 0:16:47.556 Jerry's Sadoff. He's this guy who has more vaccines approved 0:16:47.596 --> 0:16:51.716 than anyone alive. So things like guarda cel MMRV that 0:16:51.796 --> 0:16:55.316 all children take. You have the coronavirus vaccine from J 0:16:55.476 --> 0:16:57.756 and J the one shot, and you know, I think 0:16:57.756 --> 0:17:00.476 fourteen vaccines have been approved under his watch. It wasn't 0:17:00.516 --> 0:17:03.236 just that he had done a huge amount of like 0:17:03.276 --> 0:17:05.676 the modern vaccines that define the modern health era. It's 0:17:05.716 --> 0:17:07.956 that his hit rate was unusually high, Like it wasn't 0:17:07.956 --> 0:17:10.076 like he worked on one hundred get to those fourteen 0:17:10.156 --> 0:17:12.636 he had, Like his ratio of success. 0:17:12.276 --> 0:17:13.796 Was unusually high. 0:17:13.956 --> 0:17:15.556 And that told me I wanted to work with them, 0:17:15.596 --> 0:17:17.676 And so I called them up and went out to 0:17:17.676 --> 0:17:19.356 have dinner with them, and I was like, Jerry, you 0:17:19.396 --> 0:17:21.596 told me this universal vaccine technology is the only thing 0:17:21.636 --> 0:17:23.676 you thought was worth a damn like, come join me 0:17:23.716 --> 0:17:25.276 and like, let's kick a hole in the universe. And 0:17:25.316 --> 0:17:28.076 so he came. And the reason I'm telling you this 0:17:28.156 --> 0:17:30.636 is that he didn't just come in with phenomenal clinical plans, 0:17:30.676 --> 0:17:33.756 which he did. He also came in with some strategies 0:17:33.796 --> 0:17:35.196 where he's like, one of the things I've noticed for 0:17:35.236 --> 0:17:38.636 both the coronavirus vaccines and the RSV vaccines was that 0:17:39.116 --> 0:17:42.116 the folks who added in little mutations to keep those 0:17:42.116 --> 0:17:45.596 spikes stable, those vaccines were successful, and the folks who 0:17:45.596 --> 0:17:49.156 didn't add in good stabilizing mutations their vaccines were unsuccessful. 0:17:49.236 --> 0:17:49.796 Huh. 0:17:49.836 --> 0:17:51.756 And he said, I think that that's just a critical thing. 0:17:51.796 --> 0:17:55.156 You want to trap these spikes in their stable forms 0:17:55.156 --> 0:17:57.276 so the immune system can target what the spike looks 0:17:57.316 --> 0:17:59.596 like before it a tax a cellar before it falls 0:17:59.596 --> 0:18:01.156 apart to confuse the immune staff. 0:18:01.276 --> 0:18:04.116 So, just to be clear, like the spike proteins, it's 0:18:04.156 --> 0:18:07.916 the hema glutenants that are in nature on the outside 0:18:07.956 --> 0:18:11.716 of the of the of the flu virus. They have 0:18:11.756 --> 0:18:14.396 a three dimensional shape, right, Yeah, they can change three 0:18:14.396 --> 0:18:17.356 dimensional shape, and that actually turns out to be important 0:18:17.396 --> 0:18:20.316 for sort of simple mechanical like a key fitting into 0:18:20.356 --> 0:18:23.476 a lock. Reason right, and it's and they don't if 0:18:23.516 --> 0:18:26.116 you rip them off the virus as you are when 0:18:26.156 --> 0:18:28.756 you're presenting them in this vaccine necessarily stay in the 0:18:28.796 --> 0:18:30.676 shape you want them to stay in. That's a o. 0:18:31.036 --> 0:18:33.276 They're kind of like a little three prong grappling hook 0:18:33.316 --> 0:18:35.636 and they change shape in order to like hook into 0:18:35.636 --> 0:18:38.236 the cell membrane and then tear it open. And they're 0:18:38.276 --> 0:18:40.156 designed kind of like with hinges because they need to 0:18:40.156 --> 0:18:42.036 be able to be mobile and make changes. And so 0:18:42.076 --> 0:18:44.996 this protein is not inherently stable, but what you want 0:18:45.156 --> 0:18:47.036 is you want the thing very stable because you want 0:18:47.076 --> 0:18:50.356 the immune system to train on defeating the trimer when 0:18:50.356 --> 0:18:53.356 it's in it's sort of cocked and loaded, but prior 0:18:53.396 --> 0:18:58.196 to shoot position. And we've seen with RSV and coronavirus 0:18:58.196 --> 0:19:00.756 that that was absolutely essential for the successful vaccines. 0:19:01.076 --> 0:19:03.156 And so anyway, Jerry came in was like, we should 0:19:03.196 --> 0:19:03.756 do this with flu. 0:19:03.956 --> 0:19:06.836