May 19, 2017

Bootstrapping a Better Vaccine

by StartUp

Background show artwork for StartUp

The Story
Jake Glanville and his small biotech startup are trying to beat big pharmaceutical companies and major research institutions to a potentially game-changing medical breakthrough: the universal flu vaccine.

The Facts
Mark Phillips wrote and performed our theme song. Build Buildings wrote and performed our special ad music. Additional music by Bobby Lord, The Centennial, Donny Carma, Drexler, Get Better, Jupyter, and Tyler Strickland. David Herman and Mark Wilkening mixed the episode

Where to Listen


LISA CHOW: From Gimlet Media, I’m Lisa Chow. This is Startup

LISA: Biotech— it's an industry that requires a big investment of capital, a long waiting period to see if a scientist can prove out his or her theory, and then a tiny chance of a massive return. And that's why innovation in the biotech space has so often happened inside major research universities and pharmaceutical companies. But increasingly, young scientists are moving outside those institutions and starting their own companies. Some people call it the 'biohacking' movement. On this episode, we have a story of one of those 'bio-hackers' -- a guy who came up with an idea, and decided a breakthrough in vaccine research was more likely to happen in a small town in Central America than inside Pfizer or Stanford. StartUp producer Bruce Wallace went to Guatemala; that’s where our story begins.

BRUCE WALLACE: Last month, I found myself on an overgrown hillside, standing in front of a low cinder-block building.

JAKE GLANVILLE: Alright so this is the facility, We’re going to put on gloves

BRUCE: Jake Glanville, the biohacker I was here to see, was about to introduce me to his research subjects. But first... we had to take some precautions.

JAKE: We’re going to chlorinate our feet to make sure we don’t track anything in. So just go ahead and step in here.

BRUCE: We sloshed our rubber boots through a chlorine bath, then made our way into a large, fenced-in yard.Jake is trying to revolutionize the way we vaccinate people for the flu. It could give us ways to manage other viruses, too … and save hundreds of thousands of lives ... He’s doing this ... using pigs … an animal that until a couple years ago Jake knew absolutely nothing about.

JAKE: So I was looking at like people who have pigs as pets. They have these lists of things to do with the pigs that they're real smart and they'll get bored if you don't give them toys. They get sunburned easily. Things like that.

BRUCE: Jake is 36. He’s tall, with glasses and curly black hair that corkscrews erratically around his head. When he’s deep into a scientific problem he listens to Nicki Minaj songs on repeat; when he likes something he says it’s “deluxe.” His big idea about how to revolutionize the flu vaccine hit him back in 2011. He’d studied genetics as an undergrad at Berkeley, and had worked his way up to being a principal scientist at the pharmaceutical giant Pfizer, working on developing new medicines…One day, he was heading home from work.

JAKE: I think I was on my motorcycle, I had music in my helmet which I’m sure I shouldn’t be doing but I did.

BRUCE: The idea Jake had was a way to create a universal flu vaccine.One single vaccine that could protect against all the thousands of strains of flu...Here’s the thing you need to know how the flu works: the virus is constantly mutating and changing … we face new ones every year … so every year scientists have to race around and create a new set of vaccines to fight it.But around the time Jake had his realization, scientists were focusing on this one spot on the flu that doesn’t mutate.

JAKE: A spot that can’t mutate and that gives you a way to force the immune system to target it. You know in like Star Wars when they say there’s a weakness in the Death Star? It’s like that, you’re basically spotting a weakness in the Death Star.

BRUCE: Which means if you could make a vaccine that targeted that spot … it could protect against all flus.

JAKE: Yeah, all flus forever. It’s the last flu shot you’ll ever need.

BRUCE: A universal vaccine. This would be a big deal. Because those seasonal flu vaccines … they’re not perfect. At best they’re 60% effective. That’s part of the reason up to half a million people die from the flu every year.And the vaccine industry doesn’t have a big incentive to fix this -- the market for the annual flu vaccine is worth about four billion dollars. Despite that … several years back a bunch of scientists started trying to develop universal vaccines, including ones to hit that death star spot … that spot that doesn’t mutate. But it turns out -- that’s really hard.

JAKE: The problem is just how to get these damn antibodies to hit the right spot on the virus.

BRUCE: It sounds, for someone who understands one percent of it, it sounds so frustrating to know exactly where the spot is and all this science has been pointed at it and you just can’t, it just can’t hit the spot.

JAKE: It’s amazing, no, the immune system has ADHD. There’s this site that doesn’t change, every once in awhile somebody gets lucky and gets the right antibodies against it, but most of us miss.

BRUCE: And this is what hit Jake as he was riding his motorcycle home from work that day ...a new way to train the immune system to hit that death star spot. Jake wasn’t actually working on vaccines at the time, but he was reading a lot about them. The problem tripping up scientists was that when the immune system recognizes a flu virus, it attacks the virus from all sides, with all kinds of antibodies. Instead of making only antibodies that target that death star spot. Think of shotgun spray when what you want is a sniper’s bullet. Jake’s epiphany was a way of basically teaching the immune system to recognize its target. He would show the immune system that vulnerable death star spot over and over again. So the antibodies would focus in on that one spot, instead of getting distracted and attacking some other part of the virus...Jake remembers rushing home to his computer to see if his idea could work.

JAKE: And it was beautiful. I could feel the heartbeat in my head. When you see something that’s that cool, I think I remember thinking ‘This is too beautiful not to be real.’

BRUCE: If Jake could prove this idea worked, he could create a vaccine that would save the lives of not only the hundreds of thousands of people who die from the seasonal flu each year … but potentially millions more than than that.

JAKE: Every 10, 15 years, we have a major pandemic that hits, and they can kill a million people easily, and back in 1918 there was a flu pandemic that killed 51 million people.

BRUCE: In other words if his idea for the universal vaccine worked … it would mean the end of the flu as a public health threat to humans.

BRUCE: So, when Jake had this idea, he got really excited. But he also started feeling anxious … anxious he might be wrong. But also anxious that he might be right … because he knew proving his idea could take over the next decade of his life.

JAKE: You’re trying to kill the idea as quickly as possible, because you’re either going to like kill the dragon or ride it. if it’s real, it could end up swallowing up my life but If this thing works it alters the human relationship to health. And so I was just like no goddamnit I'm going to try this.

BRUCE: One problem with that was -- Jake knew Pfizer wouldn’t go for it. He’d been there for four years, and seen them pass on lots of innovative, outside-the-box ideas.

JAKE: There's actually a formula, and I'm sure Pfizer is not unique in this there's this formula. This is how valuable the project is. And one of the features in the formula is how many other people are working on it. If you're the only one working on it you think that will be valuable. No, that counts against you because it is a greater risk.

BRUCE: So Jake quit. Five years ago, he and two former Pfizer colleagues launched a startup called Distributed Bio. They had a couple of ideas for products they could get to market quickly. And they figured they could use the money from those products to fund the vaccine research. It was a gutsy plan to finance his big idea. At first it seemed like it was all working out … Distributed Bio licensed their products to a bunch of pharmaceutical companies. Jake started a PhD program at Stanford, to get more biology and computer modeling under his belt. But after a year, they hadn’t made enough money to get the vaccine experiments going. And at the same time huge pharmaceutical companies like Sanofi Pasteur, and academic powerhouses like Scripps and Harvard -- were making progress on their universal vaccines. Jake was feeling the pressure.

JAKE: I just felt constantly anxious that I had this cool idea and I was squandering it by not working on it. And you know I have all these e-mail alerts and news articles or papers come out and I get like a little mini heart attack every morning I wake up and it's the first thing I do I check and some titles will come out that freak you out or I'm like oh god someone did it. And then you check you know like OK no that's not what they did.

BRUCE: How many of these news alerts did you have set up?

JAKE: I think I have like 12 of them like everyday I get some. BW: And each time you see one you're like oh god is this it. JG: Yeah it's like one of ... It's like one of them it’s weird little ritual

BRUCE: So the plan for funding his vaccine experiments had failed...Jake’s next idea: VC funding. Venture capitalists were starting to pour a lot of money into biotech -- four and a half billion dollars in 2012. Jake thought the first phase of his experiments would cost about a million dollars. But when he started approaching VCs … he ran into a new problem. You can drop out of Harvard and still get VC money to grow Facebook … but in biotech, VCs look for credentials.

JAKE: In biotech people who lead things have Ph.D.s. And I didn’t. And they want to know who thought of this. How does how do you know how do you know enough breath to make sure your idea is right and who the hell are you. I think that was another question I would get from the VCs a lot.

BRUCE: Scientific research is expensive, and it takes a long time. So investors look for evidence that an idea could prove out. “Come back when you have more data,” they kept telling him. This is actually a real problem for people trying to move new scientific ideas forward. It’s hard to turn a concept into data without money. This gap between concept and proven-concept is wide enough that people actually have a name for it -- the biotech valley of death. So, VC money wasn’t going to fund Jake’s experiments. But he had one more idea: Maybe there was a way the experiments themselves could generate some cash...Jake knew that he’d have to prove his vaccine on animals before he could test it on people.

JAKE: My thinking was, ‘Why don't I work on an animal market where we can make money in veterinary science on the way towards humans.

BRUCE: Jake had been planning to hire a contract lab which would run his experiments on mice. But no one would buy a flu vaccine for mice.

JAKE: So I called my buddy at Zoetis, and I said, ‘Hey Is there an animal that there's a vaccine or an interest in it in a vaccine for that has a virus that rapidly mutates. And what's the biggest market?’ And so he said well of course it's flu and pigs. He's like 165 million dollars a year. That's a big market. There are vaccines right now and they have to change them every year and they have all the problems that human vaccines have. And so like as soon as I hung up the phone with him I called my father afterwards and was like, ‘How much does a pig cost in Guatemala?’

BRUCE: How much does a pig cost in Guatemala? And how do you do biotech in a place where there’s no biotech.That’s after the break.


BRUCE: Welcome back to StartUp....The leap Jake made to doing his vaccine work in Guatemala isn’t as random as it sounds. He grew up there, in the town of Santiago, a bumpy three-hour drive from Guatemala City. Jake’s dad still lives there, and runs a hotel in town. When Jake had the idea to test his vaccine on pigs, he had two thoughts: first, pigs are raised commercially back in Guatemala. And second, stuff is cheap there. Jake’s dad told him, a pig … costs 50 bucks. And suddenly Jake saw a way to get his experiments done: he only needed about 30 pigs to get started … and he had the money for that. Plus he knew there was some unused land behind his dad’s hotel. And his brother, who works in construction, could build a space for the pigs. So here’s the scheme he pitched to his co-founders, Giles and Chris: he’d ship his vaccines from his lab in San Francisco down to Guatemala, and inject it into the pigs there. Then he’d draw blood samples from the pigs, and ship them back to the states, to find out whether the pigs were having the response he was hoping for. He needed to do that testing in the US because it had to happen in a lab with a higher bio-safety level.

BRUCE: To like an uninitiated person coming to them and saying I've got a solution I’m gonna build a facility in Guatemala I'm going to ship vaccine down there to ship blood back. It sounds like kind of a crazy work around. Was anybody like what you're crazy.

JAKE: Yeah. You know it is complicated. I think people who Chris and Giles and stuff they knew I grew up down here for them it was the numbers. I just was like Look here I think I can make this work. It's got to be instead of $900,000 for this initial round of experiments. I'm going to be spending like about 80 grand is what I estimated at the time.

BRUCE: 80 thousand dollars … versus nine hundred thousand dollars...Today behind the hotel, there’s a cinderblock building and fenced in yard where the pigs live. There’s a beatup soccer ball and some chew toys to keep the pigs from getting bored. A specially built overhang lets them get out of the hard Guatemalan sun.

BRUCE: Wait why aren’t they going after you?

BRUCE: When we first arrive, a half-dozen pigs swarm around me, inspecting the cheap rubber boots I bought the day before coming down here. They gnaw and pluck at them, and do this weird sucking thing around the top.

BRUCE: Ok ok ok. I can’t imagine they’re that tasty. They taste like Target. Cheap Chinese Target shoes.

SARAH IVES: Hi piggies. Hi. You look so good

BRUCE: This is Sarah Ives. She took the lead on running the lab down here. She’s fond of the pigs, even decided they should have names: Elloin Degeneres, Kim Kardashioink, Spamela Anderson, Squeeyoncee, and Pink...Cute, but these pigs are not to be trifled with.

SARAH: Pigs are very powerful and have very strong jaws, they can basically crush you.

BRUCE: Now you tell me.

SARAH: Oh yeah they can rip your hand off if they wanted. But they give you little love bites to say hello.

BRUCE: The pigs were injected with vaccine a week ago. They’re getting blood drawn today to test if the vaccine is prompting the right antibodies. So we start herding them into the cinderblock building...Inside, the pigs are brought to the vet one by one. An assistant has a long pole with a metal ring around the end. He slides it over the pig’s lower jaw to restrain it. They take some vitals to make sure the pigs are healthy, and then begin the blood draws. Before they start, the scientists put in earplugs.

JAKE: Alright let’s kick off. SI: Oh earplugs BW: Oh, it’s that loud?

SARAH: The first pig is always the calmest, because it doesn’t know what’s coming. So as the day goes on and we go through more pigs, they scream more loudly, because they get agitated from the previous pigs.

BRUCE: So this is calm?

SARAH: This is about as calm as it gets.


BRUCE: Jake and I watch a couple. Then head out.

BW: That is definitely the most horrifying noise I’ve ever committed to tape I think.

JAKE: Yup, I warned you.

BRUCE: The blood draw only lasts a couple minutes, and the pigs seem to recover quickly.

A few minutes later, the first two of them, including that calm one you heard screaming, are back outside playing in the sun.
BRUCE: Jake and his company are saving a lot of money by working down here. But they’ve run into some pretty big problems they wouldn’t have if they were in the States. There have been bureaucratic snafus: one compound they needed to make their vaccine got stuck in customs--passed back and forth between the ministry of health and the ministry of mineralogy because neither knew which was supposed to sign off on it. The additive spoiled before they figured it out. And there’ve been other hurdles a lot of founders don’t have to deal with. Early on, Jake may have cut some corners.

JAKE: More than you might think, there's probably planes where people are-- for good reasons-- immunologists are moving weird stuff around in their socks or if their luggage without listing it appropriately. People do what it takes sometimes to get the work done.

BRUCE: What have you done?

JAKE: I have all my approvals in place. [Laughs]

BRUCE: Jake didn’t want to go into detail on tape. They haven’t only had to navigate bureaucracy. There’ve also been some wilder problems. Like this one time, eight months into their work in Guatemala. They had the first full round of samples ready to send back to the states; the samples that would show whether all of their work was on the right track. To get the samples out of Guatemala, Jake had to deliver them to a shipping company in Guatemala City. But then, that morning…

JAKE: I wake up and my scientist who was with me at the time sends a text that says, ‘So I’m hearing that there was a murder in town and now we can’t leave. I’m not sure I’m understanding. The murdered person was Mayan, part of an indigenous group called Tz'utujil.

JAKE: Tz'utujil people are super-polite but they’ve put up with a lot. They were occupied during a 30-year civil war. A lot of Tz'utuji died during that war, killed by Guatemalan paramilitaries. At the time Jake was trying to get his samples out, cops in town had been squeezing the Tz'utujil for a few months. Asking for bribes, and for free stuff from stores...And so these these jackasses were going around and demanding stuff free stuff from people and I guess they were really drunk one night it was the night before we were about to leave and they went and tried to demand free booze from a cantina which is like a little Mayan bar and the guy running the cantina is like, ‘No you need to get out of here.’ And one of the cops drew his gun and he killed the guy.

BRUCE: A crowd chased the cops to the police station, and demanded they give up the cop who’d shot the guy. Protesters lit a police car on fire. Others went out to the edges of town and blocked all the roads so that reinforcements couldn’t get in. Jake’s driver called from outside of town.

JAKE: He's like look man I can't get to Santiago they blocked the roads. I can't get into Santiago and I'm like mean you can go meet you and he goes no that's not a good idea. And I'm like What do you mean he's like now. People are really angry is better you stay away. And at that point I had this dry ice cooler with all of our samples in it. But the dry ice evaporates. And so I thought I might have two more days left but maybe not. And then I'd be losing all these samples.

BRUCE: Driving out of Santiago was out of the question. The town is on a lake and normally it’s easy to get in and out by boat. But Santiago’s mayor had just tried to escape that way, so the protesters shut down the docks. They told all the boat drivers that if they tried to pick anyone up... they'd set their boats on fire.

JAKE: And so all the boats left and everyone's like, ‘Yeah no we're not picking up in Santiago.’ So I started calling guys I knew in San Pedro. And finally one of them was like All right. That is a special day is it going be a special price. And I was like whatever takes man just come straight to Santiago boat docks and then let’s leave immediately. And so that's what he did. He showed up we like had our stuff ready just dumped it right in the boat and then we bailed and we were leaving went across the lake and as we got on the other side of the lake we could see helicopters flying over toward Santiago And they sent in like a massive number of like. I mean there were cops who looked like shock troops right to go like reassert control. But we made it out. We had the samples and we're able to bring them up to the states.

BRUCE: Once Jake got those samples out of Guatemala, they were ready to analyze their first round of results. It was a moment of truth.

JAKE: Your theory could be wrong. You could have that the vaccines went bad in transit, maybe you processed the samples incorrectly, maybe the pigs had been treated weirdly maybe they secretly all got sick you didn't know about it and it screwed up their vaccine response.

BRUCE: The whole team was back in San Francisco for this moment...In their lab, Sarah put the samples into a grid of small tubes. Each tube contained a sample from one pig. To test the samples, Sarah added an enzyme to each one. If the pigs were responding to the vaccine the way they hoped ... making antibodies against different strains of the flu ... the tubes would turn light blue. The control samples on the other hand would remain clear. So what they wanted to see was a mix of blue and clear tubes.

BRUCE: When she started to see results, Sarah called Jake who was on his way in.

JAKE: And she’s calling me and I’m driving down and I’m like, ‘How’s it look?’ Because I knew if nothing was responding the plate would not turn blue at all. If they all turned blue at all there was some problem. What I was expecting was polka dots. What I’m expecting is polka dots. And she goes Jake it's polka dots. So I got into the lab. //That's when the first time when we saw like that technique was absolutely working we're getting the super broad reactivity against a whole bunch of viruses that go back to like 1918 which is the pandemic H1N1 that killed 51 million people.

BRUCE: For four years, ever since that motorcycle ride, Jake had been following a theory. Now he had real evidence that he was onto something.

JAKE: So there's a photo of it. It's like us sitting there like 8 p.m. on a Friday night and everyone still laugh because they want to see the results. And like I teared up I had like take my glasses like the stupid photo be taking my glasses off. It was emotionally overwhelming to have all that like fear and like all of the hope and fear all twisted up inside you and then you looked at the data and it was beautiful it wasn't just like half of a signal it looked gorgeous and it was kind of inspiring and overwhelming. And it was you know it's something you're like scared to let yourself be too excited about. But then you see that moment you realize how much you've been hiding that from yourself. And the truth is of course you wanted that you wanted that the whole time.It was a major victory, but they’d need a lot more of those.

BRUCE: Before they could say that their technique was showing promise, they'd need to do multiple rounds of testing on three separate groups of pigs...It’s been more than a year now since those first results. Jake and his team are planning to finish the pig tests next month. If those results look good, they could start making money from a pig vaccine. But if Jake wants to make a vaccine that doesn’t only work for pigs but also for people, he’s going to need a lot more money.

BRUCE: Does it still feel like you’re in a race?

JAKE: Yeah, yeah absolutely it does. Because I still feel like I’m in a David and Goliath situation.

BRUCE: Say more about that.

JAKE: Well you know we’re still a tiny operation, I’m still running experiments in Guatemala to get this done. There's other ways to get this done faster if you have huge resources behind you. And I haven't had that.

BRUCE: A couple of months ago -- the quest for funding brought Jake to Washington, D.C. He was in town to pitch BARDA. It’s a research arm of the federal Department of Health and Human Services that focuses on pandemic-sized threats. Like Zika outbreaks and anthrax letters...Jake and I caught a cab to the meeting.

BRUCE: Of all the times you’ve pitched this, how important is this one?

JAKE: This one’s much more important because BARDA, BARDA would pay for human trials, they’d pay all the way to the FDA. So that’s $30 million for the phase 1s...

BRUCE: To make a human vaccine, Jake will need to do another round of animal trials, followed by trials in people. And BARDA is one of only a few organizations that could move that work forward...We pull up in front of a modern, stone and green-glass office building, one block off the Mall...The cab driver had been listening to us talk.

DRIVER: Hey good luck on your presentation, Okay? It sounds very interesting. Thank you.

BRUCE: Jake hustles in with his computer...A few hours later, I meet him outside.

BRUCE: Overall did it go as well as you’d expected?

JAKE: So it was um medium-good. It went super long and they were excited about all the tech. But Perfect would have been ‘Yeah we’re going to do human right now. They didn’t like write a check at the meeting. That would have been the perfect outcome. They didn’t just kick us out and be like, ‘Yeah this was stupid.’ Now I’m just exhausted That was like three hours wasn’t it? Uggh.

BRUCE: The BARDA scientists pointed out some drawbacks to Jake’s plan. One flagged that FDA approval could take a really long time, because of all the viruses in his vaccine. Another wondered if it would work as well in humans as it had in pigs...Not surprisingly, Jake has an alternative plan. The Gates Foundation. They funded some of his PhD work, and Jake has been in touch with them about his vaccine research. When he found out the head of their infectious disease program was gonna be at Stanford, he decided to stop by.

JAKE: And so I showed up and they were a bunch of other people still there and there was this other professor who was sitting down just wouldn't get up and leave.

BRUCE: Jake told me the story on the phone the next day.

JAKE: And so I was sitting there thinking like oh my god are you kidding me. I’m not even going to be able to have this conversation. I was like I'm just going to get an uber and driver to the airport so I can have a one-on-one. But then the conversation shifted and she's the one who brought it up she said hey so we've been looking at your universal vaccine work we're really interested in some ways we can apply it. And then we started having this conversation and just rolled from there. And basically went over the experiments that we’d conduct next.

BRUCE: And what what kind of possibilities does that open up for you?

JAKE: It's huge. It's huge. Right. So so far I basically came up with this idea and had I thought it was too beautiful to be wrong. So I had to test it. And I had to come up with money // and build a company that support the infrastructure to be able to test the hypothesis. Them coming in means I don't have to test one thing at a time I can parallelize and we could test more than just influenza. We can start testing the HIV applications. And I’d like to partner with someone like Gates so we can give it away in the developing world.

BRUCE: The HIV applications … This is the hope of a lot of scientists who are working on the universal vaccine. That the technique could be applied to other viruses that mutate quickly. Like HIV...But that’s still really far off. His conversation with the woman from the Gates Foundation was promising… but it was also preliminary.

JAKE: You know there's not a solid commitment yet. Like here's the experiments. Here's what we're going to run. Here's where they're going to run. You know here is how much money is involved. So I don't want to get myself too excited till I see that stuff lineup.

BRUCE: Partnering with Gates or BARDA would put Jake near the end of the biotech valley of death -- that funding gap that plagues startups like his. If Gates comes through, he thinks he could be doing the first human trials of the flu vaccine within months...To get to where he is now, Jake started his own company. He spent five years improvising and dreaming up ways to do science outside of major research organizations. In other industries, that’s enough time to build a successful business, maybe even sell it off. But since Jake is in science, he’s just getting started.

LISA: Bruce Wallace is a producer of Startup...Next week on StartUp: What it’s like to start a company when people don’t necessarily want to buy what you’re selling.

MEGAN: How long am I going to have people telling me that the food that I'm making is disgusting... Like, do I have to be the crazy bug lady, and for how long?

LISA: Crickets, worms and crazy bug ladies. That’s next time on StartUp...StartUp is hosted by me, Lisa Chow. Our show is produced by Bruce Wallace, Luke Malone, Simone Polanen, Emanuele Berry and Amy Standen. Our senior producer is Molly Messick. We are edited by Caitlin Kenney and Pat Walters. Production assistance and fact checking by Alvin Melathe.

Mark Phillips wrote and performed our theme song. Build Buildings wrote and performed our special ad music. Additional music by The Centennial, Donny Carma, Drexler, Get Better, Jupyter, Tyler Strickland, and the true gentleman Bobby Lord.

David Herman and Mark Wilkening mixed the episode.

Special thanks to Ben Kuebrich, Natalie Jones, Ian Setliff, Doris Bucher, Jean-Marie Silverman, and Ryan Bethencourt.

To subscribe to StartUp, go to Apple Podcasts, or whichever app you like to use. Or check out the Gimlet Media website: You can follow us on Twitter @podcaststartup.

Thanks for listening. We’ll see you next week.