Making a Universal Flu Vaccine
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Vaccines train your body to make these antibodies that protect you against deadly diseases. It's a thing you get so you don't get sick in the first place. And it's so clever and so elegant and so obviously useful. I think it is honestly fair to say that vaccines are truly one of the greatest inventions of all time. On the very short list, they've saved hundreds of millions of lives. Give me all of them. Give me all of the vaccines.

But I got to say, the flu vaccine sucks. The flu vaccine sucks. It really does. And for a somewhat simple reason, the flu virus mutates so quickly that we can't come up with vaccines fast enough to keep up with it.

So every year, scientists develop a new vaccine. But even in the time it takes to manufacture that vaccine, the virus keeps mutating. As a result, even if you get a flu shot every year, there's still a good chance that you'll get a bad case of the flu. Last year's flu shot, for example, was only about 35 percent effective. And so for decades now, scientists have asked a fairly obvious question.

Is there some way to come up with a flu vaccine that would work not just for the strain of flu that is circulating right now, but for almost all strains of flu, including strains that haven't even evolved yet?

I'm Jacob Goldstein, and this is What's Your Problem, the show where I talk to people who are trying to make technological progress. My guest today is Jacob Glanville. He's a bioengineer and an immunologist, and he's the founder and CEO of Centivax, a company that's trying to make a universal flu vaccine.

A flu vaccine that will consistently and reliably prevent people from getting the flu. You imagine talking to a generation that didn't have flu anymore. They would think we were nuts. They were just like, oh yeah, every year we have a circulating pandemic. And then six months later, there's another one. And yeah, you know, 50,000 people die, but what do you do? And like, that's nuts. But we take it for granted. The vaccine that Jacob's company, Centivax, is developing for flu is likely to go into human trials next year.

The company is also in earlier stages of developing universal vaccines for HIV and COVID, among other diseases. And wildcard, they have also worked on creating a broadly effective anti-venom for snake bites. We talk about snake bites later in the conversation. To start, Jacob told me about the moment he first got the idea for a universal vaccine.

It was around 2012. He was working for the drug company Pfizer. And he wasn't working on vaccines, but he was doing something related. His job was to identify antibodies that could be used to treat disease.

And at this particular moment, he was studying antibodies that would bind to a particular protein called PCSK9. And so I was riding back on my motorcycle one evening and I was reflecting on this problem where there's this target called PCSK9. It kind of looks like Mickey Mouse's head. And they really wanted antibodies against kind of where the neck is. If you get an antibody there, then that can affect cholesterol and lower cholesterol.

The problem is that they were getting antibodies against the ears and they weren't getting antibodies against the neck. And so I was trying to figure out, is there an engineering way to sort of focus the immune system at arbitrary sites that would save me a bunch of time? And I started imagining, what if I were to take that target, not just from humans, but from like a donkey and a

an alligator and a chicken and like just take a swath of different versions of that. They were different just about everywhere up in the ears, but they were the same down where the neck was. And then if I mix those together and I diluted each one, there wasn't enough of any one of the species of PCSK9, then maybe only the neck would be the thing which was shared across all of them and the entire immune system would focus on that. So like in total, the sort of sum total of...

of the mix, it would be like a lot of neck. The neck is conserved. The neck is what is the same. And there's only enough of that to induce the antibody response. So that then if you, whatever, inject that into an animal or a person, what the person's immune system is going to see is a lot of neck. Yeah. And so they finally focus on the neck instead of getting distracted by the ears. That was the principle.

And so I got home and then at a certain point I realized I was being an idiot. And what this was, was not a way to save a few months on an antibody discovery campaign, that this was a potential window opening to the, to the Holy grail of vaccine science. The Holy grail is that,

All of the major viruses that we're confronted with, flu, influenza, HIV, Ebola, these viruses mutate and change. Yeah. But they always have some little spot that they cannot mutate. And those spots are always super important. That's why they can't mutate it. Because if you mutate it, the virus is no longer infectious. Yeah.

And normally they get away with it by having distracting areas and most of the surface that can mutate. And that's why we have to update our flu shots every year. Distracting, meaning distracting to our immune systems, like our immune system. Oh, I like that. I like the ears. I like that shiny part on top. And that's exactly. Yeah, yeah, yeah.

Yeah. Basically the conserved Achilles heel is a small site and most of the surface can vary and it can't, it gets away with not changing the critical site by varying lots of stuff around it and taking advantage of the fact that the immune system doesn't know the difference. And so the ability to focus the immune system against a conserved site would be the basis of a universal vaccine because instead of targeting one strain of flu or one strain of coronavirus or one strain of HIV, uh,

you could target the shared sites that the virus is never allowed to mutate. And if you do that, then you're suddenly hitting the entire class of influenza viruses, including future ones that haven't evolved yet. Right. I mean, that part of the idea is the part everybody knew already, right? Like, that is the relatively obvious idea. It's like, don't go for the part that changes. Go for the part that's the same, right? The hard thing is how do you do that? So had...

When you describe the idea of like, oh, just take a bunch of different ones, dilute them, mix them together, nobody had thought of that before?

Yeah. So surprisingly not to your point, people since the nineties were aware of these conserved sites. And so they knew where the sites were. We had crystal structures. It was just how the hell do you get the immune system to focus on those sites was the problem. And people have tried a couple of different things. They tried chopping out parts of the protein, but then, then the site you're interested in falls apart. It's like trying to grab a snowflake. It'll melt in your hands. Um, they tried a couple of other techniques that didn't work out.

So, okay, so you have this new idea for how to make a universal vaccine that nobody's tried before, which, to use flu for an example, would mean you take a bunch of different strains of flu, and in particular the sort of spike protein of the flu that your immune system sees. Then you dilute them and mix them all together in a single vaccine.

So what the patient's immune system winds up seeing the most of is the part that's the same in all those different strains, the part that doesn't change. And then ideally, the patient will develop antibodies to that part, the part that doesn't change. And therefore, the patient will be immune to like almost any strain of flu. Yeah. And you recognize it might not work, right? You always are like, look, this is a pipe dream, but like I could not go to sleep because I was like, if this works, this is such a stunning breakthrough. Yeah.

It's hard to sleep when you're thinking about that. It sort of becomes all-consuming. So you get this idea, and you're working for Pfizer, a company that makes vaccines, by the way. What do you do? Again, I was not doing anything involving their vaccine group. Important for intellectual property reasons. I was not working on vaccines at Pfizer. I resigned. So I did two things. I started...

my first company, Distributed Bio, and I also applied for the PhD program in immunology at Stanford. And you do this because of your idea? Yeah, yeah. Because basically, I applied to the PhD program because I was like, if I'm wrong, I need to stop thinking about this. I need to surround myself with brilliant immunologists who can kick holes in this, and I need to be able to make sure I'm not being myopic. And

And then if I'm right, I need the world to hear me. And so I need to be a card-carrying PhD immunologist from Stanford so that people go, okay, this guy isn't just some Yahoo. And then for the company side, I just saw this opportunity to be able to go test it. Because originally I did go out and I tried to talk to some VCs in 2012, 2012.

And I think they're, you know, predictably their answer is like, what the hell is this and who the hell are you? And you had a bachelor's degree, right? And you'd worked at Pfizer for a couple of years, like a million other people. So not, you know, you can't blame them. I was like, I guess I'm nobody right now. Let me go fix that. Yeah.

And, and so I decided that I was going to go found a company because there was some there was some work I was doing at Pfizer that I'd created some publications on using the deep genomic sequencers to look at the immune system and then building better antibody libraries with what we learned about that.

And I realized there was a business that could be built on that. And my intention was to build that business and use it to subsidize some of the early proof de-risking experiments on this universal vaccine concept. And so that's what I did. So I just did both for five years and didn't sleep that much until the PhD, graduated from that. And then later I sold the first company, Distributed Bio. So the company you start, you're selling, your clients are drug companies, essentially, right? Yes.

But you're doing that. That's sort of your side hustle. That's sort of funding your vaccine dream, right? And while you're doing that, you start doing this research on your vaccine in pigs in Guatemala, right? Yep. Tell me about that. The background is I grew up in Guatemala. My parents are Americans, but they met in Guatemala in the 70s, and they built this hotel and restaurant with my grandmother. Hippie dream? Yeah.

Yeah. The hippie dream. That's exactly what it is. There's, there's small hippie enclaves down there. And then there's most of the village is to will Mayan. And then there's catchy cows and some other Mayan communities. And it's, it's very beautiful lake. So it makes sense that the hippies would go there. Yeah. Uh, the civil war largely drove them away, but my family, when I was a little boy, they went down there to try to fix up and sell the property. And then one thing led to another and we ended up becoming in keepers. And so I grew up in, in the village. Um,

I think it probably had an effect on my interest in immunology in the first place. And I had this connection to Guatemala and I ended up maintaining a connection to USAC, which is the University of San Carlos, the national university. And so fast forward in my career to when I was thinking about universal vaccines, like one of my, let's say one of my deep impressions left from some work at Pfizer was this, I was very impressed with a group that was doing animal health work because I felt like

Instead of using mice, they would often ask, what's the most relevant and similar animal model to humans for this indication? Mouse is not a person. No animal is a person, but you can find something that's a closer fit and waste less time on failed translation. And so I had this technology. I was trying to figure out where to apply it. I actually called one of the guys, and I was like, what's the veterinary market that has a rapidly mutating pathogen that's also found in humans? Uh-huh.

And he said, it's definitely flu and pigs. They get the flu. In fact, they transmit it to humans. And so pigs are definitely not as convenient as mice. But I felt that the data would be much more meaningful because they actually get the flu. So I ended up doing it back in Guatemala with Erwin Calgua, my collaborator at the University of San Carlos.

And some property that my father had. So I ended up making some calls. I found out we could get the pigs. There was a vet who was involved in the H1N1 2009 pandemic shift monitoring. You're doing it in Guatemala because it's cheaper, basically? You're offshoring your research? Yeah, it's way cheaper. Yeah, radically cheaper and faster. I think the cycle time is astonishingly slow to do animal studies and ask for grants. Like, you're lucky to get a study done, like, once every two and a half years, according to the U.S. model. Mm-hmm.

Whereas in Guatemala, the costs were radically cheaper. I could build a facility to spec and I was, you know, I'm an engineer, so I need to be able to do cycles. Yeah. Yeah. And so this enabled me, I think we ran five studies there over a couple of year period. We were able to go pretty quickly, go in and do rapidly de-risk.

this universal vaccine technology in a way that was economically feasible given the growing profits, but still finite profits that I had from the antibody discovery and software side of the business. So when you're doing those pig studies, I mean, just to return to your initial idea of using essentially different strains, let's say, you got to figure out

what's the right concentration? Because if you do too little, you don't get any meaningful immune response. And if you do too much, then you're getting immune response to the parts that are not conserved, to the parts that you don't want immune response to. Exactly. I was just proving the concept, right? Because I think there's definitely people who are like, this isn't going to work. There's no way.

And look, if I'm wrong, then it doesn't matter if I put 15 things in. If each one's below the dose and they're not interacting like I was hypothesizing, then you should see no immune response, right? So I could have just been wrong. That's the other thing I was testing to see, does the principle hold? And the answer was definitively yes. So, okay, so you have this idea that it works, right?

Somewhere around here, you sell... I don't know which one is the side hustle and which one is the main hustle. I guess vaccinating pigs in Guatemala sounds like a side hustle, even though it's the thing you really care about, right? You sell Distributed Bio and you spin out Centivax, the vaccine company, right? And then what? Then where are you? Yeah. So it was a good time. So we got...

The Gates Foundation awarded us this in the Pandemic Threat Grand Challenge Award to test the vaccine no longer in Guatemala, but up in American facilities that had biosafety containment so that we could challenge the animals who've been vaccinated with these strains that had evolved after the mixture. So we

deliberately pretended it was 2007 and only included strains up to 2007. Then we challenged the animals with the 2009 pandemic shift virus, a 2012, a 2017 virus. That's a big question, right? It's like testing something that's out of the model, right? Like it's saying, okay, we give somebody this vaccine and then there's a new kind of flu. Does it work? Yeah. Yeah.

And it felt that that was essential, which by the way, those same pigs, we pulled their serum out of the freezer over the last couple of months and they neutralize the H5N1 that's currently outbreaking in cows and chickens and some people. Uh-huh. The bird flu. The bird flu. It creates super broad immune response. Yeah. So the timing was good. CRL wanted to buy. I was happy to do it. And, uh,

My condition was, I'm like, look, I want to take this universal vaccine technology with me to a new company. And they agreed to that. That was December 31st, 2020 is when the sale completed. And so basically January 1st. That is a remarkable time to go all in on a universal vaccine, December 31st, 2020.

We transitioned over January 1st, 2021. I am now the CEO and founder of Cinevax. And I started calling an army of geniuses of the best people that I've worked with to gather together. And I was like, look, this is going to be the big one where... It's like a heist movie, like Ocean's Eleven or something. It was like the best people of my entire career I worked with. You don't need a lot. You just need every person to be exceptional. And if we do our jobs right, we touch the long arc of history. Yeah. So...

So what have you figured out? Like, what have been the key things you've figured out since then? We identified a couple extra people we brought in, including Jerry Sadoff. He's this guy who has more vaccines approved than anyone alive. So things like Gardasil, MMRV that all children take. You have the coronavirus vaccine from J&J, the one shot vaccine.

And, you know, I think 14 vaccines have been approved under his watch. It wasn't just that he had done a huge amount of like the modern vaccines that define the modern health era. It's that his hit rate was unusually high. Like it wasn't like he worked on a hundred to get to those 14. He had like his rate ratio of success was unusually high. And that told me I wanted to work with them. And so I called him up and went out to have dinner with him. And I was like, Jerry, you told me this universal vaccine technology is the only thing you thought was worth a damn. Like come, come join me in like, let's kick a hole in the universe. And so I,

He came, and the reason I'm telling you this is that he didn't just come in with phenomenal clinical plans, which he did. He also came in with some strategies where he's like, one of the things I've noticed for both the coronavirus vaccines and the RSV vaccines was that the folks who added in little mutations to keep those spikes stable, those vaccines were successful. And the folks who didn't add in good stabilizing mutations, their vaccines were unsuccessful. Huh.

And he said, I think that that's just a critical thing. You want to trap these spikes in their stable form so the immune system can target what the spike looks like before it attacks a cell or before it falls apart to confuse the immune system. So just to be clear, like the spike proteins, it's the hemagglutinins that are in nature on the outside of the flu virus.

They have a three-dimensional shape, right? Yeah. And they can change three-dimensional shape. And that actually turns out to be important for sort of simple mechanical, like a key fitting into a lock reason, right? And they don't, if you rip them off the virus, as you are when you're presenting them in this vaccine, necessarily stay in the shape you want them to stay in. That's a problem. Yeah.

They're kind of like a little three-prong grappling hook and they change shape in order to like hook into the cell membrane and then tear it open. And they're designed kind of like with hinges because they need to be able to be mobile and make changes. And so this protein is not inherently stable, but what you want is you want the thing very stable because you want the immune system to train on defeating the trimer when it's in its sort of cocked and loaded, but prior to shoot position. And, and yeah,

we've seen with RSV and coronavirus that that was absolutely essential for the successful vaccines. And so anyway, Jerry came in and was like, we should do this with flu. I had a bunch of experience stabilizing proteins from work. We did stabilizing antibodies at Pfizer. And then also my company distributed bio. And so, um,

We ran a quick campaign and we identified these great stabilizing mutations and they had like a pretty stunning effect on the quality of the immune response. So you're doing this basically atomic level engineering of the proteins, right? That's a thing. Go on. What else? And then the other thing, the major thing we've done is we started the manufacturing. We advanced the program, not just for flu, but we're also, we have data validating the universal coronavirus vaccine. We're testing on HIV, um,

We're testing on malaria and a number of other pathogens right now to be able to create a portfolio. So those have been some of the major activities in the last couple of years. When are you doing human clinical trials?

Yeah, so we've got about nine months left of manufacturing, or eight months of manufacturing, and then you spend a month getting permission from the FDA to start your study. And then we'd start human trials. So, okay, so next year, you're starting human trials next year. So when you think about the future, the future of the company, of your work, like, what are you worried about? So...

I worry about less and less things. And then the things I worry about evolve. So in terms of, is it going to be safe? I worry about that extremely little. We have been vaccinated with influenza HA protein since the 1940s. It's actually the best validated diverse class of versions of HA compared to any other vaccine that's been tested. And it's the history of safety has been extremely good.

We're using the Pfizer BioNTech mRNA chemistry, so you can get a non-exclusive license to it. That's the same one they used for the COVID vaccine. Yeah. So it's been in billions of people. So we know what the safety profile is. So safety, I'm not concerned about. In terms of efficacy, like how well it works, I basically don't believe in any one animal's immune system because you could always overfit. The immune system could overfit in a certain bizarre and unpredictable way.

And so we've tested this in pigs, but also ferrets, also rats, also mice, also cows, and also human immune organoids, which is organ donors offer their lymph nodes. They're smushed up and you basically create a bunch of little mini lymph nodes from a donor and you can vaccinate them under different conditions to see how someone with a lifetime of immune memory, including to flu and vaccines would respond to our vaccine or a control vaccine.

And when we did that, as well as all the other animals, we consistently saw this universality effect. And so going into the human trials, I think we're pretty bullish that the effect is going to be dramatically better than...

uh, the current vaccine. So I think we're going in assuming that the human trials probably will perform well, but I want to say I won't sleep well at night until I get that data. And I'm like, okay, yeah, we're, we're, we're on solid footing. I, I, we've done everything I can to de-risk it with these other organisms and, and even human immune organoids. And now it's time to run it in humans.

Fundraising is always a headache where we've got now at least multiple groups gathering around with term sheet options and we're looking at them. But it's been, just to put it lightly, a difficult period for biotech fundraising. Now, we've managed to survive where a number of other companies have not. But, you know, I'm probably gained some gray hair and probably, you know, took away some of my health span as a consequence of surviving this period.

I mean, does that last thing mean you're afraid of running out of money? That's what I mean. Every company worries about that. That's the nature of venture. We've managed to pull it together and we just got this grant which covers us. But the fear is that we're stuck, that we need to go continue raising money so that we can go pay for the rest of manufacturing and pay for clinical and everything.

an arm for the next parts. And, and to be blunt, this has been an absolutely terrible period in biotech. So we got 75% off on all of our equipment for my entire laboratory. Cause we got it from auctions. A lot of this stuff was in like new stuff in boxes where a company just ran out of money and they're stuck. And I benefited from it. I've benefited from being able to hire remarkable people that otherwise were struggling to find an opportunity because of it's, we've basically lived in this like, uh,

a little bit of a biotech hangover after I think there was too much investment and sometimes it's some pretty goofy stuff during the pandemic for biotech. And I think we're in this like a little bit of a headache, a little bit of a macro economic global uncertainty area. And those things have both slammed up against biotech in an unproductive way. Yeah. So, okay. What's the happy version of the story? The happy version is that our vaccine works the same as it has in all those animals and organoids that we've seen and

We bring it forward. Universal vaccine just becomes the vaccine because that's suddenly a vaccine that you take and you don't get sick.

The first thing it does is it creates a massive improvement in global health. And then the major impact of, you know, flu kills people, right? It gets a lot of people sick. People lose a lot of time from school. Pregnant women in their second trimester that get flu are seven times more likely to have a child with, with schizophrenia and they're adult. Like there's a bunch of like squalor and consequences of,

But the biggest effect is that when this gets out there, the pandemic era is over. And when you say pandemic, you mean flu pandemic. Yeah, the flu pandemics are over, which is our most common source of pandemics. We had five in the last hundred years. We had two or three per century before then. So they got faster. We have a lot more people. We have these pig mega farms. We need to fix this.

And with this vaccine, you no longer have a pandemic era because you have a decent proportion of the population that's already immune to the new virus strains before they hit. And that's what the new world looks like. And so that's the happy version for flu. But our intention is to do that for every pandemic pathogen, to just one by one go and end the pandemic era, to come up with countermeasures that first protect the world from pandemics, the medical, personal, and economic costs, and

Second, protect the world from just major outbreaks. And then ultimately, I want to have these same tools can arm future decades to attempt eradication campaigns that previously were not possible. And that's the future we want to build. We'll be back in just a minute. This is Justin Richmond from Broken Record. What's summer without new music? And what's the hottest new summer song without a refreshing iced coffee in hand? Especially the new iced horchata oat milkshake and espresso available now at Starbucks.

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That's why the younger you are, the more you need AARP. Learn more at aarp.org slash wise friend. Climate disasters aren't a distant threat. They're happening now, affecting people everywhere. And just as disasters grow in frequency and intensity, wealthy nations are cutting back aid. Most disasters are predictable. So what if instead of scrambling to rebuild, we protected communities before disaster strikes?

With the human and economic costs of disaster mounting, with less aid to go around, focusing on what works has never been more urgent. Listen to Counter Crisis from the Center for Disaster Protection, available wherever you get your podcasts. Let's talk about snakebites. All right, let's do it. How'd you get into the snakebite business? Yeah, so it was 2017 and...

I think it was because the World Health Organization was announcing, you know, the neglected tropical disease nature of snakebite, kind of declaring it a neglected tropical disease. Basically saying hundreds of thousands of people are killed or very badly wounded every year by snakebites. It's not just some weird thing. And not enough people are...

They're trying to develop countermeasures. And I think what had happened... Because most of the people who die or are severely injured are super poor. Yeah, yeah. It reminds me of Monty Python, where they have the Roman Senate, and someone goes, what do we do about the poor? And then all in unison, they put up their hands and they're like, fuck the poor! All right, next. That's the neglected tropical disease story. The fundamental problem, yeah. Yeah.

I think also that, to be fair, I don't want to be fair, but like the companies that make antivenom, most of them are kind of doing it as a public service as a loss. Because most of the people who need antivenom of the millions of bites per year, they're poor. They're subsistence agriculturalists and their children and people who live in rural environments. Yeah.

And if you take that market, which is probably like five to 600 million total per year, but it's fractured across 30 to 40 products, each of those things is pretty unattractive. Just to be clear, because you need different antivenom for different snakes. Yeah, there currently is no universal antivenom on the market. And so people had started ending programs to make certain types of antivenoms. And I think that was happening in 2016. So then in 2017, the World Health Organization brings some attention to this.

And then I started thinking about it. I, you know, in my village, we had snake bites sometimes. And I just like, I like topical diseases, particularly if they interface with cool bioengineering. And I'd been working on the universal vaccine work. And so I started wondering, I'm like, you know what? I wonder if that same idea of their conserved Achilles heel that's found across all flu or all HIV. I wonder if.

Snake venom toxins have that because if that's true, maybe you don't need to make 650 different antivenoms. Maybe it's actually that you only make one cocktail of broadly neutralizing antibodies and it could work against all snakes, a universal antivenom.

And so I did a little, you know, playing around on my computer. And sure enough, there's basically like 10 major toxins that all snakes use. Nature's lazy. And then when I pulled up a bunch of sequences from a bunch of different snakes and I compared where they varied, where they mutated relative to each other versus not. Again, I found a little conserved spot. And it's the business end, right? Because these toxins can mutate, except they can't mutate right where they need to go bind your...

your neurons your nicotinic acetylcholine receptor to paralyze you and so forth and so at that point i got pretty stoked where i was like i'm pretty sure this is and like at the time no one had been talking about broadly neutralizing antibodies outside of viruses and i was like this is so cool and so then i was like all right where do i find a person who uh has been bit a couple times right and i was like looking for a clumsy snake researcher like there's like a site in uh

Costa Rica, there's a place in Arizona, there's some places in India where I was reaching out and like, I was kind of coming up empty. And then I don't know how somehow like I desperately just started like Google searching. And, and I found these insane articles about this guy named Tim Friede, who had spent,

At the time, over 17 years self-immunizing, hundreds of times with 16 different species of snake. What he did is he milked the snakes, he weighed out microgram initial doses and administered it, and then he dose escalated over a period of months up until the point that he took milligrams. And it was only after he built up that immunity that he would then have the animals challenge him.

Because no one lives... You can't live from a mamba bite. It'll kill you. And yet he is able to take it. You see that video? What you don't see is he spent about nine months building up immunity against it by starting with microgram trace doses. That's crazy. So you're like, that guy is walking universal antivenom. Yeah. If anybody has the secrets of universal antivenom, it's pumping through this guy's veins right now. And so I was like, I have to meet him. I...

Couldn't find his contact information anywhere online. And so I contacted the reporters and one of them put me in touch with them and had his number. And so I had this call and I told, I remember it super clearly and where I was just like, look, I know this may be awkward, but I would love to get my hands on some of your blood. And his response was, I've been waiting for this call for a long time.

And so what happened? And then what I do is we just scheduled 28 days apart, two blood draws. And each one was for 20 milliliters. So there was no risk as to the blood draw amount. This is like a couple of tubes. And so then that got sent over to my lab. I then processed it.

And I separated out the serum and the cells. And from the serum, I wanted to check his work. I think, you know, his story, you know, seemed credible and stuff, but I wanted to confirm. And so I had ordered a series of snake venom, which by the way, it is suspiciously easy to order the venom of venomous snakes. I have learned during this project.

I was like, this should not be this easy. Anyway, so I had a bunch of panel of snakes, some that he said he had immunized against, and I also picked ones that he never had. Oh, interesting. This is testing the universality. Yeah, yeah. And so I tested his sera, and I also tested mine and a couple other control sera on the venoms. Now, the control people, like me, who have never been bit, we had no response to the sera. He had blazingly high responses to all the venoms, including the ones he had never been exposed to, including Nugenera, like very different snakes.

So based on this, right, you come up with this anti-venom cocktail that seems like it could work against not all venomous snakes, but a lot, a lot of different kinds of venomous snakes.

You publish a paper about this in the journal Cell. Where does it go from here? What happens next? We've reached out to the Wellcome Trust and to some other groups that might be interested in this. We've also reached out to, I guess I won't say their names, but there's some pharmaceutical companies that develop antivenom to try to see if this is something they'd be interested in doing a partnership on to pick up. I think

My feeling is that I would ideally like to have a pharmaceutical partner to go develop this with or a massive support from some foundation, because otherwise it's you can make it profitable. You can unfracture that market and you could be manufacturing this and serve maybe a 500 million dollar per year profit.

But to get there, you have to go spend at least 10 and probably more like $20 million on GMP and some other early activities and then $25 million for clinical. And I think it's hard to imagine who's going to put that money up front for what is a relatively small profit, which is the whole frustrating aspect of neglected tropical diseases. That's why they're neglected. Yeah. We'll be back in a minute with the lightning round.

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That's why the younger you are, the more you need AARP. Learn more at aarp.org/wisefriend. Climate disasters aren't a distant threat. They're happening now, affecting people everywhere. And just as disasters grow in frequency and intensity, wealthy nations are cutting back aid. Most disasters are predictable. So what if instead of scrambling to rebuild, we protected communities before disaster strikes?

With the human and economic costs of disaster mounting, with less aid to go around, focusing on what works has never been more urgent. Listen to Counter Crisis from the Center for Disaster Protection, available wherever you get your podcasts. Okay, last thing is a lightning round. So as I understand it, you dropped out of school to run your family in hotel restaurant when you were in high school, or you took a year off high school. What's one thing you learned from

from that? Yeah. I think one thing I learned is that people on teams don't, that people do not crave chaos. I think people want to know what the people are calmed down by knowing that their rules, even if the rules don't benefit them. And I dropped out to go run the restaurant and I was like 15 year old kid. Uh, and you know, initially people didn't really listen to me. You know, it was just like a crazy time. And that was crazy for the employees. Cause the employees are like, I don't know, like your son's here, but maybe, uh,

Uh, you know, maybe, uh, David's going to die and my dad's going to die. And then my mom was like, let's just shut it down. I can't deal with it. I'm like, mom, we need the money to be able to go pay for the bill, the medical bills, you know? So everyone was acting chaotic and it was like extremely difficult to manage the team and try to keep people focused to do their jobs. And, uh, you know, this thing happened where, uh, one evening, uh,

one of our cooks was like walking out and he had this big bag and I went over and I was like, what the hell are you doing? And I realized he was stealing a bunch of steaks. And like, it was just steaks, but it was with a bunch of the other chefs. And I was just like, I didn't do it for a tactical reason. I just did it because I was fed up and I'm like, you're stealing from my dying father. And I just, the last thing I need. So I was just like, give it back. You're fired, go away. And they were shocked. And I was like, no, no, you're fired. You're not allowed to come back in anymore. Um, we'll, we'll send you your, your severance basically in two weeks, get the hell out of here. And like,

What I was not anticipating is the next day everybody showed up for work and suddenly there was actually everyone was calmer. And I think it was the transition of perception of power that they were like, they want, you know, I did something harsh and yet suddenly everybody's performance improved partially because they're like, okay, now I know like the hand that feeds, but it was also like knowing that there was some rules and there was a plan. And then I want to leave you with the thought that wasn't like my lesson was like, okay, be like,

the red queen all the time. That's not absolutely the way to go. That's not leadership. But I think what I did learn is that when times are difficult, people prefer to know that there's a plan and it's organized and there's a solution, even if it's rules that don't benefit them rather than having opened into chaos. And I think that was counterintuitive to me because my personality is different. I actually thrive in chaos and having those sorts of complicated choices. And I, and I resent confinement of any form, but

But I think that that actually for most organizations, that's empowering and important. And to articulate the rules and people know there's a system, then people are like, I feel comfortable because now I understand and it can work in a predictable environment. And I think that part's important. So that's something you learned running the restaurant that has helped you as a CEO. I know you recently bought the restaurant. So now you're

a restaurant owner. Is there something you've learned running a biotech company that now helps you running a restaurant? Ah, so yeah. Uh, yeah. Uh, externalizing responsibility. So I don't run the restaurant. Uh, I bought the hotel and rest or the restaurant and some of the properties, not the full hotel. Some other people bought some of the bungalows. Um, and then what I did is I basically wanted to, uh,

maintain the value of the property and increase it and make sure that all the people who some of us have worked for our family since my childhood, that their, their jobs weren't compromised, which during the pandemic where tourism was like really bad, like there was a risk of that. And so, um,

I run it essentially as a, it's a cooperative. It's really, I'm like, I don't extract financing from it. I've talked, I have basically a guy that we worked with for a long time and another team member. I've just told them like, look, my objective is for you to maintain the reputation of the place, just keep running it well and make sure I don't. And my one requirement is I need to not think about it at all. And, and, and I'm working on the universal vaccine tech. So maybe I'll, you know, in the future I'll want to go and fiddle around and be a restaurateur. But like right now I just needed to not think about it. Um,

I've heard you use the word hard-ass a few times in other interviews. Are you a hard-ass? I think on myself and on an expectation of detailed... I think research needs to be done in a very particular process. I don't think my team would say I'm a hard-ass. I think that...

Or maybe I've evolved over time. I think I have exacting standards of expectation of how to get things done. But it's more like me driven of anxiety than me going in and like, I don't bark at people or anything. I'm like, guys, we have to have a set of standards.

and then we need to run this in a certain way and we need to have things documented. Otherwise, we're just walking on quicksand and we'll just mess up every time. So no, I don't think I'm a hard ass. I think there's certain things where I have exacting expectations, but I also think that you have to have that if you want to build it. I've struggled to find an example of a big company that was built on technology where the CEO did not have that property because I think there's a certain expectation of excellence that is required to build something great. Maybe a little bit of a hard ass. A little bit of a hard ass. All right. Occasional.

Jacob Glanville is the founder and CEO of Centivax. You can email us at problem at pushkin.fm. And please do email us. I read all the emails. Today's show was produced by Gabriel Hunter Chang, edited by Alexandra Gerriton, and engineered by Sarah Bruguer. I'm Jacob Goldstein, and we'll be back next week with another episode of What's Your Problem?

Climate disasters aren't a distant threat, they're happening now, affecting people everywhere. And just as disasters grow in frequency and intensity, wealthy nations are cutting back aid. Most disasters are predictable. So what if instead of scrambling to rebuild, we protected communities before disaster strikes?

With the human and economic costs of disaster mounting, with less aid to go around, focusing on what works has never been more urgent. Listen to Counter Crisis from the Centre for Disaster Protection, available wherever you get your podcasts. Do you know who wrote All of Me by John Legend? Or If I Were a Boy by Beyonce? Or Big Girl's Song Cry by Fergie? That's me, Toby Gadd.

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