Ashlee Vance's World Of Wonder And Weirdos: New England Edition

This is MIT. What are we doing? We're at MIT, the Stanford of the East. And the data gathered by researchers here suggests that you all have limited attention spans. You've been TikTok'd into a dopamine-chasing swipe prison. This beautiful building probably does nothing for you anymore. It's very pretty.

Meow.

Kitten.

I don't want to believe the numbers, but the MIT nerds swear by them. And as we've come to learn, Nerds never lie. Tom Brady. And so we're gonna get right to it. We've come to New England to make content for you all. This content will include the world's fanciest coffee, drone submarines, cures for cancer, and brains in vats. Lobster roll. If you've made it this far, then we're in this together. Our 30-second engagement rate is soaring. The algorithm is being fed like the pig beast that it is. And that means I should stop talking and show you something cool. This is Gloucester, Mass. It's a fishing city. And all sorts of uplifting movies like The Perfect Storm and Manchester by the Sea have been filmed here to celebrate the serenity of cod life. In large part because of the fish, Fish. This happens to be the place where commercial flash freezing was invented. Shout out to Clarence Birdseye, who started the General Seafood Corporation here in 1925 with his double-belt freezer contraption. Jump forward 100 years and flash freezing in Gloucester remains crucial to our story, for we have come here to visit Cometeer. We're here!

Welcome to the first brew-and-flash-freeze coffee facility on the planet.

Thank you.

This used to be a seafood processing facility. When we bought it, literally you could find crab legs around the building. You could smell fish from about 10 feet outside, so—

And you still bought it.

We still bought it. We've shown it a lot of love over the past few years.

Matt Roberts is the co-founder and CEO of Cometeer. Some people say "comb-teer from Gloucester." It is "cometeer from Gloucester." And the fellow right by him is Alex Kaplan, the head of coffee product. These men are complete coffee obsessives.

When I got to Princeton, I opened up a coffee shop there. I spent a summer working on a coffee farm in Colombia and also took this coffee tasting certification. I ended up passing when I was 19 years old. I was the youngest Q-grader in the world.

I started off by making these pouches of frozen ice cubes to melt and dilute into iced coffee. I met George, the godfather of specialty coffee, and I showed him my early prototype, and he pretty much spit out the sample in front of my face.

He was just like, "What's with the look on your face?" Forget it, man.

But then he served me a single-origin coffee from the Borbolla region of Ethiopia, and it just completely blew my mind. So then I went into his factory, his head barista, He brewed up samples with his freshest beans. I flash froze those samples with dry ice, and it was 6 months later when we melted down the flash frozen brewed samples, and the flash frozen brewed samples tasted like they were freshly roasted, ground, and brewed that week, which was incredible. That's when the light bulb went off. We just discovered the best way to preserve coffee on the planet.

Never would have believed you would have come up with a cup like that.

Cometeer delivers the absolute best-tasting coffee on the planet from a new format flash-frozen capsule. Now we know pretty much every other coffee company says they have the best-tasting coffee, but we've proven scientifically that our process captures flavor and aroma that you just can't capture in any other packaging format. So it starts with beans from the best farmers and roasters around the world.

This right here is About 900 pounds of freshly roasted coffee beans.

We grind and brew these beans with advanced equipment at 10x strength.

The grinder's in the secret room.

The grinder is in the secret room.

Okay.

And then flash freeze the coffee with liquid nitrogen moments later, and that locks in fresh flavor and aroma like never before. The liquid nitrogen's -321 degrees. You can see the coffee being filled. All you need to do is melt this frozen little puck of coffee, that's like a super espresso shot, into 8 ounces of hot water.

The dimple of freshness.

The dimple of freshness. Or you can melt and mix and create iced coffee, latte, espresso drinks, and we all do it from a fully recyclable capsule. We capture the spent coffee grounds. A company, Black Earth Compost, picks them up and recycles the grounds in a fertilizer, and then the capsules rinse clean during use, so you can throw them right in with the beer and soda cans. Metal recycles forever, so that's us doing We've done our part.

You said we might start with one called Alchemy?

Alchemy, yeah.

So this is George Howell's Alchemy. It's a very comforting and familiar medium roast blend of coffees from Brazil, Kenya, Costa Rica, and Ethiopia. We'll take one capsule here, about 8 ounces at about 200 degrees. No machine, no equipment, just like that. And I understand this is your first sip ever of Cometeer, is that right?

Yeah. Alright, here we go. It's really good, yeah, really good.

So we'll start here with a dark roast Guatemalan coffee from Huehuetenango, and this is a pretty intense kind of like rich flavor profile. You'll get like these fudgy dark chocolate notes.

Huehuetenango.

Great name.

That's a fun one.

You definitely slurp your coffee. That's where you get a lot more of the aromas. There's thousands of different aromatic flavors you can get, and you slurp your coffee, you're going to get—

I like that one.

Nuance flavor from that.

Yeah, I like this one.

Yeah, the darker roast, nice. Now this is called the El Salvador Santa Rosa, a single origin, lightly roasted coffee. Some people say it tastes more tea-like than coffee because it's very light and delicate.

This feels chill, like it's— Yeah, yeah.

All right. Are you ready for your mind to be blown?

Yes.

So this next coffee is an extremely special coffee called the Finca Deborah Enigma Geisha from a very small region of Panama that's known for growing some of the highest quality geisha coffees in the world.

I've never smelled a coffee that smells like that. I've never tasted a coffee that tastes like that.

Yeah.

This definitely does not taste like my— whatever I make at home. It's like a different drink.

Yeah. Yeah.

Cometeer has raised more than $100 million, and a significant portion of that money has gone towards this factory.

We dumped about $85 million into the complete renovations of the facility. We can do about 200 million cups a year.

I'm trying to picture in my head what is inside that room. Is it one big machine?

Aha, there's a lot of stainless steel in that room, let's just say that.

The secret room looks exactly like this. Does the beach have a name?

Um, I forgot what the name of this beach is actually. Should know.

Matt actually grew up here, and so we dragged him away from his precious factory for some local color.

We are right outside the Bowport Hotel, the site of the original Birdseye plant. And right out in front of us every year during the St. Peter's Festival in Gloucester, they have the greasy pole competition. Anyone who is a third-generation Gloucester citizen gets the opportunity to try to run down the pole and grab the flag at the end. The young lads get a chance to show off for the lasses. It's really like a bunch of ex-fishermen who have had a few beers.

Focus, footwork equals flight.

There are people who grow up training for it in their backyards. A kid who won, he almost came to tears because it was his lifelong childhood dream.

I want to thank my mother, father, Jessica, Manny, my grandfather, well, all my family.

Dream come true.

Let it go, buddy. Viva Zapata! In truth, I just wanted a lobster roll. And I also wanted to hit Matt with a flash-freezing history surprise. Were you not at some point like, "Maybe I've taken this coffee thing too far.

I've gotten in deeper than I had intended." Well, I think the hardest moment was going out, quitting my job, and starting the company with a credit card. I actually had 4 roommates at the time. I'm just like spending all the time in the kitchen. My roommates were like, "What the hell is wrong with Matt? Do we need to have like an intervention with him and his parents? He graduated top of the class. He's just making iced coffee all day, obsessed with his iced coffee." It was tough those first 4 or 5 months before we had received angel funding. You know, just getting over that hump was a challenge.

All right, I'm gonna blow your minds. And this is when I revealed to Matt that he was among flash-freezing royalty. All right, so there's a gentleman named Cayman Hodges, okay, who's filming us right now. His great-grandfather was another gentleman named Wetmore Hodges.

Wetmore Hodges.

There's a New York Times story here on his obituary. Mr. Hodges organized the General Foods Company and the General Seafoods Corporation, both of Gloucester, Mass. In the same period, he became associated with Clarence Birdseye, and the two developed the Birdseye process of freezing foods.

No way.

Mr. Hodges negotiated the sale of his two companies and the Birdseye process for $22 million. Holy shit. $22 million before 1929.

That's like $350 million today.

$451 million.

I just looked it up. $451 million. Okay, and my aunt's Julia Roberts. You guys aren't messing with me? That's true? You should, you probably have earned the right to walk the greasy pole. I think that's what you win now.

We salute you, Wetmore Hodges. Although Cayman does wonder how your generational wealth degenerated so quickly.

So I don't know if I mentioned this, but, you know, Jim Cook was a pioneer in the craft beer industry, right? And he actually crowed funded the IPO for Boston Beer. The way he marketed to bars back in the day was super innovative. 20 years ago, craft beer didn't exist. Now it's 27% of dollar sales, and it just like took him a lot of time to get people over the hump. Specialty coffee is maybe like 15 years behind craft beer. Most people see coffee as brown, bitter water that needs the cream and sugar to make it taste good, just like people People saw beer as like water with foam on top back in the day.

Just realizing now that you're maybe hitting a sweet spot because young people are drinking less.

Yeah.

Yeah.

And caffeine is seen in a pretty good light for health reasons and then productivity, obviously.

I think it's a long-term trend in America, like the rise of the third space was the original idea for Starbucks' coffee shops, was instead of your home or the office, somewhere to hang out, and I totally think like People who drink less alcohol are more into coffee. So I definitely think it's a big trend and we're very well positioned, I think, to support it with Cometeer.

Thank you. Thanks so much. How many lobster rolls have you consumed?

A lot.

A lot.

This is the land of lobster roll.

There we go. Why, yes, that is a Brex card. And you know what else a Brex card can buy? A totally natural transition to this thing, which is not really meant to be dangling in the air at all. It's meant to swim. It's the DiveLD autonomous undersea vehicle from Anduril. In other words, it's a robot submarine, and we shall see it do its thing in the water soon enough. Anduril—

Anduril—

Anduril—

Anduril Industry, in case you haven't heard, Anduril is a defense technology company started by this guy, Palmer Luckey. He's the Oculus headset inventing, mullet sporting, rather eccentric dude. Do you think that NATO should be armed with squirt guns?

How about sternly worded letters?

Would you like that?

Who is out to make a full arsenal of autonomous weapons for the US and its allies. Anduril has drones and planes and weapon systems and fancy software to tie all of this stuff together. And then it has these subs. There's the Dive LD, which is smaller and for looking at and listening to things happening in the ocean. And then there's the Dive XL, which is a real fatty and does stuff we can't talk much about. Anyway, let's get into it. I'm in Quincy, Massachusetts. Oh yeah, out in Quincy. You pronounce it like that even though it's spelled like this, because it's Massachusetts, and people here want to be made fun of forever. It's a boat we can't build anymore. Quincy is just outside of Boston and has been an industrial hub for hundreds of years. Last century, this was a lively shipbuilding center. But as you can see by this ancient sub, those glory days are gone. Perhaps you know this already, but the US can barely make ships now. Which brings us back to Androl. It wants the US to make ships again. Only super modern ones without humans inside. And that brings us to James here.

Welcome aboard the Encourager.

The Encourager?

This is the Encourager.

He helps run Androl's submarine division and used to work at Dive Technologies.

Dive Technologies was the precursor to Androl's maritime footprint. Since early 2022, Following our acquisition by Anduril, we've been working to rapidly ruggedize the sort of original concept of the DiveLD.

Today, James and I are on a mission. Yes, we have boarded the Encourager, helmed by Captain Jarrett and this load of seamen, to put the DiveLD to the test. We got about an hour 20-ish steam out. This is our Quincy Basin where we keep all our assets. Today we're actually going to be doing a survey zone just southeast of Mass Bay. What are these made out of, these panels?

These panels that we're looking at today are actually a reinforced composite. If we peeled the panels off, you would see small tubes inside this vehicle to protect the electronics, the computers that need to stay dry, but everything else inside the vehicle is flooded with water.

So a normal submarine, obviously you're trying to keep totally sealed.

Everything's got to stay dry. People inside, they like to stay dry.

This just seals the important stuff.

Exactly.

Yeah.

And these are made These are.

And then they will be made in Rhode Island.

That's right. So we just cut the ribbon on what will be a 150,000 square foot facility in Quonset Point, Rhode Island. We will have the capacity in that factory to build up to 200 Dive LDs per year.

Okay.

Which compared to our current rate, which is closer to 12 Dive LDs per year, is a pretty significant step change.

Yeah.

This vehicle is configured with what we call a geophysical inspection suite. And there are actually 5 payloads that this vehicle carries. Just below where the break in the panel here is, this is a sensor that we call a side-scanning sonar. Side-scan sonar is essentially capable of producing acoustic imagery of the seafloor that looks to your eye like a photograph.

Okay.

So let's say you want to find an undersea cable. The type of sensor that you would use to actually locate the object of interest is going to be something like a side-scan sonar. Sonar. The other sensor that's associated with that is an instrument we call a sub-bottom profiler. So let's say the mud turns into gravel, then turns into rock. You'll actually see where those transitions happen.

But are there more sensors, James?

The next sensor we carry is a multibeam echosounder that is used primarily for mapping.

Go on, James. Keep telling me about your sensors.

Two more sensors on this vehicle. One is a magnetometer, almost like a metal detector. The very last sensor is a camera. We also do take real pictures. We're going to pick up the speed a little bit, so—

We're ready to send on the survey mission.

Okay.

She's going to go down. It's on the order of 400 meters an hour. Okay. So it's going to dive down?

It is. Yep. She goes now. So it picks up some speed and she's under.

It's like James Bond. It is kind of spooky how it's there. It is spooky, man. Yeah.

So the vehicle is on mission now, which typically means we can't see what it's doing, except what we do have is This is our user interface. This is the Lattice screen.

Lattice is one of Anduril's crown jewels. It's the software that lets people track what all of the company's autonomous systems are doing out in the world. It has map info, diagnostics on the hardware, and tools to conduct missions.

In this data field, you can see basic information that tells us what it's doing in an instant in time. If you look over here, you can see Basically, the vehicle is currently running at 20 meters altitude off the bottom. It's about 60 feet. The vehicle's actually just made a turn. So we completed one track up this box. You can see the vehicle swinging around, coming back.

This rectangle, that's where you want it to stay?

That's the bounds of the survey box that we're running right now. The other neat thing about Lattice, all of our engineers, all the software developers, they can follow along. They can keep track of what the vehicle is doing.

We're just the labor.

We're just the labor today. I'm sorry.

It's going to come back up. Oh, there she is! There she blows! I had no choice. Forward, forward, forward! Battery set. Guys, lower it down and hook it. A few moments later.

All right, what we were doing was operating over a known feature, and if you look closely at what's in this image, you can sort of make out what appears to be some rocks sitting on the bottom of the ocean floor. That's exactly what they are. This is an area that we've mapped many times. And so what we're able to do is come back to this exact area if we want to make sure the sensor data has processed through Lattice matches the sensor data that we've collected before. This is the bottom of the ocean, right? So you're kind of looking at a picture that's been taken of the bottom of the ocean, but it's been taken with acoustic energy. And you can see in this piece of the image, we actually have two objects that are on the seafloor. They look to be old anchors, old ship anchors that have been deposited on the seafloor. So the value to data like this is you could say, "Hey, maybe something is new that didn't used to be there," or, "There's an object in the area that I want to go investigate," and you'll know exactly where it is, and you can go back to that spot, you can take a closer look at it. If you need to, you can move or recover the object.

Along with the sub we've been hanging with, Andrel also has this big boy, the Dive XL. It can do longer missions, hold more stuff, and it's been developed alongside the Royal Australian Navy to make what the Aussies call Ghost Shark. The US is in desperate need of learning how to make maritime hardware again. China builds 200 boats for every one the US makes, which should make you sleep easy at night. And now we pause as the host takes a sub selfie, and then we make another totally natural transition to this sweaty bald man. This episode is going to get real weird. You have been warned. "Get his toes in your armpit a little more." "Yeah!" That man on the mat hails from Croatia. He's a doctor, and he has a PhD in neuroanatomy. He's smart, and he likes to do jiu-jitsu to stay sharp and fit. He also, well, he also gets human brains delivered to his startup's office, and he puts the brains in a machine he built, and it's all kind of miraculous. If you're into the miraculous and can stand some brains. Keep watching. Our story kicks off in New Haven, Connecticut, home to Yale University. The coeds are coedding. Some of them are on their way to Old Money 101. Others are heading to the Majesty of Lawsuits seminar. Each person on your screen will one day be president. It's all idyllic and wholesome. Not far from the campus, there's also a brain being delivered. The man working with the brain is another Croatian doctor, Josip Buković, who everyone calls Joe. He's preparing the brain to go into a machine that will restore its molecular function. The brain won't be alive in a thinking or feeling sense, but it will be doing biological things.

The brain is ready.

The point of all this is to give us a new way to test drugs meant to cure brain diseases. To explain, let's go back to our jiu-jitsu man.

My name is Volodymyr Grysylla. I'm a physician scientist and CEO and co-founder of BackCIRC. BackCIRC is the world's first intact human brain lab. It is physically impossible to conduct experiments in the human brain. You can't go to a human being and conduct experiment in the living human being. So we're trying to work around that issue by taking a dead human brain and see if we can restore, again, certain cells or molecular activity. Joe brought the brain up and he's now gonna connect the brain to our device. He's gonna interface the vascular system or the blood vessels of the brain, and at that point we're gonna start to push the fluid throughout the brain.

So down there he was inserting some, like, infrastructure connectors.

Yes, each brain that comes is a bit different. Some blood vessels need treatment, and so he fixed a couple of the blood vessels to make sure that we can push fluid through about the brain.

It's like oxygenating it, giving it nutrients.

So nutrients, electrolytes, some oxygen.

Anyone else have a brain perfusion device at all?

As far as we know, no.

No, okay. Doing anything with human brains is really difficult. Usually we use mice and then go into primates, then you test the drug in humans and it just doesn't work the way it was in the animals. And so that's part of what you guys are trying to solve.

Yeah, so we are solving the translational issue or inability to take benchtop science and consistently put it into therapies.

Their goal is to study how brains interact with drugs in the hopes of making better medicines faster for conditions like Alzheimer's and Parkinson's. Okay, so there's one in there, one in there, and then one here.

Yeah, so we have, uh, Parkinson's, we have ALS, and the non-diseased brain. This one is Tony.

Tony?

Yeah.

Like Tony Stark?

Yes, sir. We name them after superheroes because they are doing a cool job.

All right, so the brain is in this central spot.

Yes. Fake blood goes through. We have artificial lungs, we have artificial heart, we have artificial kidney.

And then if you want to inject a drug, you just start to put it in into one of these fluid compartments?

There are a couple of syringes there. The big one on the right-hand side is actually injecting a compound now, and we are testing a drug against Parkinson's disease.

What is—

there's like 5 or 6 things going on.

Yeah, so we are looking at blood pressure, we are looking at the brain's resistance against the flow, we are looking at the dissolved gases in the blood. There are hundreds of numbers being recorded every second. Each brain or device They are making vast amounts of data that no one else in the world exists.

This is weird because it's like super sci-fi thing of the future, like in a Home Depot. We made this as cost-effectively as we could.

Yeah, yeah. It looks scrappy, but it gets the job done, yeah.

Part of Bexorg's special sauce is an actual special sauce. It's a nutrient-rich fluid made from, well, worms.

So this is a concentrated solution of a particular protein that we use to carry oxygen, and it's extracted from the worm.

What kind of worm?

A Canadian night crawler.

So that is like a filtered brew of night crawler blood.

Yeah.

Okay, and then that gets mixed with something else.

With something else, yeah. And then at that point, we have our final artificial blood that is used for brain support.

Okay, okay, crazy. One of my favorite movies growing up was The Man with Two Brains. Bought you a pair of wax lips. It's brilliant and hilarious, and it raises the obvious questions people have about this work. Are the brains actually not thinking or feeling? It's a natural place where people's own brains will go, right? It's like, what's going on?

Yeah, no, like, it is a question that we get because of the nature of the work. But these brains don't fire, they don't have EEG, so there's no consciousness. It's just the cells and molecules that are present in the brain are doing their job.

So there's no higher-level thinking, consciousness, all that. It's, it's just the So you're going to the part of the brain that is doing like the base functions of operation.

Yeah, we start from zero. These brains are clearly dead. They've been dead for hours. We just discovered that there is retained experimental capacity in those brains and we exploit it now for drug discovery.

Bexor grew out of research done at Yale. In 2019, famed neuroscientist Nenad Sestan, yet another Croatian MD-PhD, stunned his peers with the release of a paper in Nature. It showed that he and Zvonomir could restore brain activity in pigs that had been dead for hours.

So once the heart stops, brain cells don't instantly just die. It's a gradual process. So we discovered if you take the isolated brain and we put it in a particular environment context, we are able to harness that gradual decay and use it to do science that was otherwise impossible.

The work made scientists rethink their assumptions around how quickly brains deteriorate and the nature of death itself.

There's definitely this dogma of, "Soon as the heart stops, brain cells are gone." That's what people— we were all taught this. And so I think there was a bit of going against the dogma. We ventured into this new field from the left field. We just wanted to develop a tool and we started like building the whole thing like ground up.

In 2022, Nenad and Zee started Bexorg to take their research from the lab and then turn it into the basis of a company. To learn more about why they do what they do and to get into these heady questions, I decided to make Nenad and Zee cook a Croatian dinner for me at Nanad's house.

Oh, you're here!

I'm texting you.

How are you?

Good, doing well.

Nanad, Ashlee.

Hello, how are you? Nice to meet you, man.

Nice, welcome to my home.

Thank you so much.

From where I grew up, this is a homemade sausage, okay? Mediterranean diet is misunderstood. People eat cheeses, sausages, and stuff like It's a very family-oriented society. If you don't know how to play cards, in my village you are finished. I mean, there's nobody gonna marry you. It's not a joke. You have to understand, my parents didn't go to college. They live in the same village. My mom goes with acceptance letter, say, "Should I let my son go to United States?" 'Cause she didn't understand how good the school is.

Yeah, you had gotten into Yale. Yeah, yeah.

My mother would always say, "My Mercedes is in America." Did you bring what your mom made?

Yeah, some of my mom's stuff, yeah.

Yeah?

So here.

Looks good, man.

It's basically a Bosnian pie, but it has no meat, so it's made with the cheese and spinach. So she is visiting, she rolled the dough herself, prepared the dough, she made the cheese. We'll just bake it half an hour. I love this stuff, this is my go-to. Hopefully we don't ruin it.

Okay, and then you do more Mediterranean.

I will make It's a type, it's called gregada. So it's basically, think about bouillabaisse or cioppino with no water.

Okay.

Basically dry fish stew.

Okay.

Thank you. And what you do is you put fish down, okay?

Okay.

So the way it works, you put layers.

Okay.

Of onions and tomatoes, okay? And then you put little bit of garlics.

This is the only show that combines brain research Croatian cooking.

We can start new show.

Okidoki.

Okay, okay, get yourself a plate.

Amazing, thank you.

Thank you.

So 10 years ago, there's tons of people doing tons of brain research, but nobody else had really bought into this idea that you could revive it in this way. Is that right? That is true.

I had some of the most famous neuroscientists push me on the side and say, "Nenad, why are you doing that? Your other work is amazing." And I worried because you have this like, "Oh my God, what if it doesn't work?

Everybody will be laughing." He cried the first time we gave him blinded samples.

Because you saw the sales coming back?

Yeah, we saw sales were recovering. For years, people on the team would cry. They were like, this is never going to work. Yeah, this is dumb. And we just plowed through and keep on going. So it got burned a bit. It's because of you.

You see, where is my thank you?

Yeah, let me try one.

Should we try it?

Yeah, yeah.

We should have baked it a bit more.

But you know what? Still incredibly delicious.

Awesome. Okay.

Bon appétit. Dobartek.

Dobartek. Yeah. Enjoy.

Oh man.

Mmm.

Okay, I wanted to ask you guys one question. Mm-hmm? I mean, when you first started doing this research, you knew that there were gonna be people who were gonna worry, like, is the brain alive?

We spent a lot of time thinking before we did anything. That's just number one.

Yeah.

But if you have a chance to test a drug, let's say like Alzheimer's disease, where we cannot do pretty much anything. And you have a chance to speed up drug development, test safety, efficacy. I mean, who are you to deny people that opportunity?

That's the key.

And you have to do it with a lot of thinking, reflection, and moral consideration.

And now we make the natural transition back to Boston, because we're going to try and cure cancer, and this is the place to do it. Thanks to their excessive number of top universities, Boston and Cambridge runneth over when it comes to biotech-minded humans. It seems like everyone here has a PhD or two. Nerds are celebrated, even the bike racks. Are shaped like molecules. There is truth that Boston can be too sedate and structured. The biotech startups here do not tend to move as fast or take as much risk as their Silicon Valley counterparts. The baggage of tradition can be self-defeating. Every now and then, though, someone does think quite big. And we're gonna tell you the story of such a person. I have really good news. Today our nation has achieved a medical miracle. We have delivered a safe and effective vaccine in just 9 months. I don't know if you guys remember, but a few years ago there was a pandemic, and then there were these mRNA vaccines that appeared out of nowhere. Oh, do it again! And they were meant to thwart the pandemic. And then people kind of lost their minds. Are you a vaccinated person?

I'm not answering that.

It would be a lot of fun to spend the next half hour going through the pros and cons of the vaccines. I'm sure the engagement in the comments section would be fruitful and rewarding. I was a guy who did not want the COVID vaccine, but I do want research on mRNA. Sure. But we're going to go ahead and fast forward to the future of mRNA and We're going to do it with this man. I think it's fair to say you guys are trying to cure cancer.

Yeah, as a, as a place to start.

Yeah. This is Jake Becraft, the co-founder and CEO of Strand Therapeutics.

My LinkedIn, the first thing that it says is making medicine move faster. I really view mRNA as the future infrastructure of medicine, and that's what we're building.

Founded in 2017, Strand was working on mRNA technology before the world knew it was a thing.

I moved to Boston to do my PhD starting in 2013. My PhD lab that I joined, 6 floors up, there was this startup that had just come out of stealth. They were called Moderna.

There is more hope on the way in the nation's fight against COVID-19.

Massachusetts-based drugmaker Moderna announcing its vaccine is nearly 95% effective. Effective.

They were doing mRNA technology, and we thought mRNA is this incredibly promising tech. It essentially is a very fancy way to deliver proteins into a cell.

The M in mRNA stands for messenger. This is because mRNA delivers instructions to your cells telling them what proteins to make. Beecraft and his co-founders have long thought that that they could use mRNA to create very precise medicines. If, for example, you have a cancerous tumor, they wanna make a therapy that goes straight for the tumor and leaves the rest of your body alone.

We're trying to get the mRNA to go into the tumors, have the tumors create a protein that the immune system will then recognize and come and kill those cells because we wanna take the tumors out. The tumors can be all over the body. They can be deep inside of the body, they can be in the lungs, they can be in your liver, and you don't want the immune system attacking any of the healthy cells. That's where you get, you know, all sorts of toxicities that are associated with cancer drugs. And so we want to program the messenger RNA to be able to say, "I'm inside of a cancer cell. I should actuate my program and cause this protein to be produced." But if it ends up in the liver cell or in a kidney cell, then Nothing happens. The program is inert. No protein that causes the immune system to respond is gonna be produced. And that is very difficult. We spent 6 years before the company started working on that tech, and then we spent the last 6 years here really perfecting it and now taking it into patients.

Some of Strand's most impressive work to date has come through a clinical trial in Australia around skin cancer.

Our first program that's in the clinic right now has treated about 35 patients so far, most of whom have, you know, stage 4 melanoma resistant to existing therapies. This is from the first cohort of patients we treated starting summer of last year. So this patient had stage 4 aggressive metastasis, started with melanoma on their skin that then had metastasized into their bones, into their muscles, and into their lungs. All of these smaller black masses are tumors in this patient. You can see just the absolute extent of disease that this patient was dealing with. And so we went in with our drug, injected into, you know, a single one of these tumors, and then every 3 weeks the patient comes in. So what happened between here and what I'm about to show you, when the patient had come back in, in between one of their injections, all of their tumors disappeared.

It's gotta be insane when you see this for the first time.

Yeah, you know, when this patient entered our trial last summer, it was probably unlikely they were going to make it to Christmas. And instead, at Christmas last year, they had no detectable tumors. And, you know, ideally they're going to see Christmas this year and many more years to come.

Yeah, very cool. In a moment, we shall head into Strand's labs, but before we do Let's have the briefest of looks at Boston's rich history. There's this scenic place and this monument and this monument and old Ben Franklin. This nation was built by people who wanted something bigger and better. They were true founders. Be like a founder and switch to Brex. Oh, do you need these?

I forgot my badge.

I don't know if your badges will work for our lab or not. Thank you.

After you.

And we're back. Cool. Strand has started with cancer, but it wants to create mRNA technology that can go after a wide variety of diseases.

I don't view us as an oncology company. I view us as demonstrating success in oncology to start in order to help develop this new era of medicine.

It's inside these labs where it's trying to build the machinery that could make mRNA therapies mainstream.

So this is an unstained slide of a very thin section of a patient tumor biopsy.

Okay.

Now in its current state, this is a white piece of tissue, doesn't really reveal much. But what we are trying to do is really combine this 300-year-old technology with our fully automated robotics light stainer.

And what, it just puts like a dye?

Yeah, it is dispensing dyes and special reagents onto these slides, and these dyes are designed to identify some key biological components in the tumor.

Okay.

And the staining process can take 3 to 12 hours, but this is all automated, so one can just load the slides and walk away and really come back to high-quality data. So once the slides are all stained, we bring them here, and this is our really high-throughput digital scanner— again, very reproducible and automated. And what we've done What we've done is we've added different kinds of colors to identify different regions in the tumor. And when we apply this to drug development, we can really see where our drug is going in the tumor, which cells it is affecting, and if the tumor is shrinking in real time.

It's great to see the tumor shrink. It's great to see the tumors disappear from patients. What is really powerful though, in terms of learning about these medicines and trying to make sense of how our drugs are working so we can make them even better in the future is peering inside of the tumors. And what we're able to do with this sort of high-throughput technology is really industrialize this process. Since day one, we knew we need to invest in manufacturing. We need to figure out how to make these drugs scalable. And if we have a drug that costs $50,000 to manufacture to treat cancer, that's going to be hard to get to as many patients as we want to.

If we took the example of the melanoma treatment, how much would that cost in 10 years?

For our trial right now, our drug costs about $100 to $200 per dose. So our manufacturing costs hopefully will come down even further with time. But right now it's incredibly scalable. As we saw during the pandemic, you can make mRNA at scale. The vaccines were like $100, right? And you were able to build doses for millions of people at that scale.

Strand's early results are promising, and the company sits at the intersection of biotech's most important recent breakthroughs. The issue, per usual, is proving that the early results can be turned into something lasting. With a bit of luck, the company will be a success, and the rest of us will have personalized cures the likes of which we've never seen before.