Science Said It Was Impossible To Do This To Brains

Our story kicks off in New Haven, Connecticut, with a human brain being delivered right here through the doors of a startup called Bexorg.

The man working with the brain is a 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. To explain, let's talk with another Croatian doctor.

My name is Volimir Reseda. I'm a physician scientist and CEO and co-founder of Big Surq. Big Surq 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 going to connect the brain to our device. He's going to interface the vascular system, or the blood vessels of the brain, and at that point we're going to 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 throughout the brain.

It's like oxygenating it, giving it nutrients?

So nutrients, electrolytes, uh, 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 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 Parkinson's, we have ALS, and a 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 into one of these fluid compartments.

There are a couple of syringes there. Yeah, 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 it 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 exhaled 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 Nightcrawler 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? Is like, what's going on inside?

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 the molecules that are present in the brain are doing their job.

So there's no higher-level thinking, consciousness, all that. It's just 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 Zvonimir 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 as soon as the heart stops, brain cells are gone.

That's what people—

we were all taught this, and so I think that there was a bit of going against the dogma and 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, Menad 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 Nenad's house.

Oh, you're here! I'm texting you.

How are you? Good.

Doing well. Nenad, 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 homemade sausage. Okay? Mediterranean diet is misunderstood. People eat cheeses, sausages, and stuff like that. 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 of onions and tomatoes, okay? And then you put a little bit of garlic.

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

We can start new show. Okey dokey.

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 cells grow? Coming back.

Yeah, we were like— we saw, you know, sales were recovering for years. People on the team would cry. They were like, this is never going to work, this is dumb. And we just plow 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, I, I We should have baked it a bit more.

But you know what? Still incredibly delicious. Perfect. Okay, bon appétit, dobartek.

Dobartek, yeah, enjoy.

Oh man. Okay, I wanted to ask you guys one question. I mean, when you first started doing this research, you knew that there were going to be people who were going to 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.