Blood farm

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It's unexplainable.

I'm Noam Hasenfeld.

And a couple months ago, the most amazing person I'd never heard of died.

His name was James Harrison.

He was 88, died in his sleep at a nursing home after a career working as a clerk for a local railway.

Just a regular guy that somehow saved the lives of almost two and a half million people.

I don't know, I still can't really wrap my head around it.

And it was just because his blood was really special.

It had this rare antibody, and doctors used it to make a medication that saved millions of babies.

But the part of the story I keep coming back to is that James had to keep donating his blood almost 1200 times.

It's not like the doctors drew blood one time, found this special antibody, and made a cure that they could end up reusing.

James, who was terrified of needles, who had to travel an hour each way to the lab, he had to keep donating over and over every two weeks or so for 64 years in a row.

It's incredible.

But the reason he had to do all this in the first place is because scientists just don't really understand

blood.

We can't store it well.

It's like putting fish in the fridge, great on day one.

Day five, not as great.

We can't reproduce it.

That's still not a reality.

And we just can't get enough people to donate it.

Roughly 40% of Americans are eligible to donate.

Fewer than 3%

actually do.

That's Nikki Twilley.

She's a science writer who just wrote this great New Yorker piece all about blood and the scientists trying to understand how it does what it does.

Because there are so many people that are dying all the time just because we don't have enough blood.

Oh yeah, I got kind of fired up writing this piece, realizing like blood loss is the most common cause of potentially preventable trauma deaths.

And wow, there are so many unnecessary deaths.

One study estimated that one in three people who died from bleeding due to injury could have been saved if we just had more blood.

But what if we didn't need to be like vampires sucking blood out of people in just the right way in order to keep ourselves alive.

What if we could just make it ourselves?

How hard can it be?

So Nikki, the first thing that hit me when I was reading your article was this thing that now that I say it feels really simple, but I don't know if it clicked for me beforehand, but just the idea that blood is alive.

Oh, yeah.

I mean, also for me, I mean, you don't, I don't know why.

We know organs are alive and they wouldn't be alive outside of the body.

But blood, because we can keep it outside of the body, I think I had just sort of thought of it like a liquid like milk, you know?

Yeah.

But no, it's alive.

It's filled with cells that are doing things and it's very hard to keep it alive outside the body, just like an organ.

And if you were to just run through the kind of basic stuff that blood does,

what are the greatest hits?

Okay.

So the biggest and most important is picking up oxygen in the lungs and releasing it around the body.

Okay.

But blood is also delivering nutrients.

It's delivering hormones.

It is taking away all sorts of toxic waste products, carbon dioxide, urea, lactic acid.

It is also playing this kind of regulatory function.

So it regulates body temperature, pH, chemical balance.

And then it has this kind of defensive role for our immune system.

So it is monitoring and raising the alarm about organ damage and about immune system threats.

So anything from a toxin to an allergen to anything that our body is like, wait, you shouldn't be here.

Is that why replicating blood is so hard?

Just because it does so many different kinds of things, that's part of it.

The other part of it is that we don't really understand how it does all of those things.

So

two challenges there.

Okay, so how are scientists trying to make this actually happen?

So I focused on two kinds of initiatives in particular.

So you can think of them as sort of the impossible burger of blood versus the kind of lab-grown burger of blood.

Okay.

So for the people trying to make artificial blood that does the same thing as the real thing, like the way an impossible burger bleeds.

I visited Baltimore where a scientist called Dr.

Doctor,

his name is Alan Doctor.

Incredible.

But he

is leading a $46 million DARPA-funded initiative to make entirely artificial blood from scratch.

It's not blood.

It's much, much tinier.

So it's not actually a beef burger.

It's an impossible burger, but it does the same job.

So how is he approaching this research?

What's his strategy to make artificial blood?

It's a really interesting project that he sort of got into by accident.

His colleague was working on synthesizing nanoparticles for MRI imaging and was like, huh, looks like a red blood cell.

So Dr.

Alan Doctor's colleague

just had this particle that coincidentally looked like a red blood cell.

Exactly.

It was a total accident.

And he ended up calling Alan Doctor,

who had been interested in blood because it was this issue in his medical practice.

And immediately, Alan Doctor was like, this is interesting.

But that's a long version of me telling you that the piece that Alan himself has been developing is the synthetic red blood cell.

And so just because it looks like a red blood cell isn't supposed to do the function of a red blood cell?

I mean, there's the way it works is it's a fatty, synthetic shell that is jammed full of hemoglobin, which is an iron-rich protein that...

picks up oxygen in your lungs, carries it safely around the body, and releases it.

And usually a chemical that wants to bind really hard doesn't want to release.

But in our bodies, there's a sort of molecule that

makes sure the hemoglobin can change shape slightly, and that forces it to let go of its oxygen.

I mean, I'm starting to understand why it's so hard to make artificial blood.

If our body is like somehow changing this molecule to slightly change shape, to pick up the oxygen and then release the oxygen.

That seems impossible to replicate.

Well, I mean, I said to Dr.

Doctor, well, so can't we do that?

And he was like, no,

no, we cannot do that.

There's an enzyme involved.

We can't build enzymes.

Like, that is not going to happen.

But he has come up with a synthetic way of sort of copying that system.

So how well does it work?

Well, I mean, when I was there, they were testing it on rabbits.

And I mean, the tenderness tenderness with which these rabbits were being treated was quite touching.

They have like a special YouTube channel of soothing rabbit musics and you know it fluffy blankets and the whole thing.

It's lovely but they drain half the blood out of these rabbits.

I mean it's extremely

the rabbits are in a really bad shape.

That is a fatal injury.

Like if you do nothing those rabbits are going to die

And then

I saw this.

The lab technician injected them with 60 milliliters of artificial red blood cells.

And honestly, within minutes, you could see the rabbits sort of, oh, like their ears started twitching again.

They were looking around.

Within like a half hour, an hour, they were hopping.

These were rabbits that were struggling to breathe.

They were dying.

Half their blood is now artificial, but they're fine.

There's a long way between rabbits and humans.

You know that.

You know, this is how science progresses.

You try it in rabbits.

You move on to trying it in healthy humans.

Eventually, you get to try it in the people that need it, i.e., humans who have lost blood.

And right now, he has very good results, but things that you didn't anticipate can emerge at any stage.

Yeah.

Have we ever gotten to this kind of research place before and then it didn't end up working out?

Oh, there is a long history of disastrous failure in this field.

One of the sort of

more

shocking failures, I guess I would say, was these so-called H-box.

H-box?

Hemoglobin-based oxygen carriers.

Oh, it's an acronym.

Okay.

Yeah.

And there was a big push for these that was actually motivated primarily by the AIDS crisis.

So the first AIDS AIDS case was in 1981.

There wasn't a way to test blood for HIV until 1985.

Wow.

So there was this span of time where if you needed a blood transfusion, it could have been carrying HIV.

It was a terrifying time.

And so it really motivated a lot of synthetic blood research.

And

two or three big pharmaceutical companies got to phase three human trials.

And it's really a simple idea.

They were like, well, hemoglobin is the thing that is carrying the oxygen.

Why don't we just get hemoglobin and inject it into people?

What could go wrong?

Yeah, what could go wrong?

So

things looked pretty good, actually, for a while.

And they got to phase three human trials, which is the final kind of hurdle before you go to the FDA and you get approval and you become the treatment for everybody.

Really, people were pretty confident.

And one of those trials, a pharmaceutical company called Baxter, I mean, the scientist I spoke to said, this was one of the most deadly trials in U.S.

history.

Wow.

52 patients got the product, 24 died

compared to only eight of the control patients.

So

it was actually shut down.

Sorry, you said 52 patients and 24 died?

Yeah.

Wow.

And the FDA shut it down.

The FDA was like, these are so deadly, they should only be trialed on people who have literally no hope of survival because they are so deadly.

So it really was this sort of horrifying kind of, you know, here were all these pharmaceutical companies thinking they had cracked it.

They're on the verge of success.

And it turns out it was a complete flop.

Everyone was like, wow, I guess we really can't make a synthetic blood.

It's too complicated for us.

We don't understand it.

And, you know, the field sort of went dead for a while.

Yeah, it just makes me think, you know, thinking about the rabbit experiment, it could seem so promising in rabbits, and then we could do it in a human experiment, and there could be something we don't know, and it could be extremely disastrous.

Exactly.

I mean, I, I love a good bet, you know, and I, Dr.

Doctor's molecule is really clever and he has really good early results.

And I don't know, I still wouldn't put money on it right now because I think there's so much we still have to learn.

I mean, we are learning a lot by doing.

I fully believe humans can get there one day, but it's a complicated project.

Yeah.

Is there

another way other than making fully artificial blood to solve this crisis?

Well, yeah, you can sort of say, well, listen, nature knows best.

Let's use natural blood, but let's figure out how to grow it ourselves in a lab.

Coming up in a minute, how to grow blood.

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Doctor, Doctor, give me the news.

I got a vacation.

Unexplainable.

Blood feels almost mythical.

During the ten plagues in Exodus, the Israelites used blood to mark their doorposts so that the angel of death would pass over their houses.

For Christians, Jesus' blood was the ultimate sacrifice.

And in Aztec cosmology, blood was what kept the universe itself alive.

But it's not like this is just some ancient thing.

We still talk about blood like this.

The American Red Cross calls blood the priceless gift of hope.

These are the people that set up shop at rec centers and libraries.

They give you a cookie and a sticker for bleeding into a bag.

They vacuum seal it.

They get it wherever it needs to go.

They're a logistics machine.

And they're talking about blood like it's the sacred elixir of the gods.

It's like we can't help being entranced by blood.

But after all of this time, after thousands and thousands of years, things might finally be changing.

Blood is starting to seem like something we understand,

something we can control, something we might even be able to grow.

Well, so this only really became an option other than pure science fiction fantasy in the 1990s, which is when we isolated human embryonic stem cells.

And so that is basically just a cell that hasn't decided what it wants to be when it grows up yet.

And if you can get one of those and you can persuade it to become a red blood cell, then theoretically you could have unlimited red blood cells growing from scratch.

No body necessary.

And it turns out, and this is how we have figured out how to grow all sorts of things like chicken muscle in a lab, what you need to do is not build a chicken.

What you need to do is figure out what are those chemical cues telling telling the stem cell that could become anything, hey, turn into a red blood cell.

And that's exactly what people who are growing lab-grown chicken are doing.

They say, what makes a chicken stem cell turn into a chicken muscle cell and grow and replicate?

And they figure out those inputs and they put the baby chicken cell in that environment.

And hey, presto, if it was that easy, we would all be eating lab-grown chicken nuggets.

And I, you know, as much as I would like to eat a lab-grown chicken nugget, I imagine that lab-grown blood has got to be way harder.

Well, I mean, in some ways it is harder, in some ways it isn't, because once you tell the stem cell that it wants to be a red blood cell, it knows how to do oxygen delivery.

We don't even have to understand how it's doing it.

We just have to understand how to make it want to become a red blood cell.

Interesting.

We aren't fully there, but the National Health Service in the UK, which is where I went, they can make immature red blood cells.

You know, the vision is that there will be like vats of this stuff, growing it at the scale that, you know, Anheuser-Busch makes Budweiser.

But the reality is that they can culture about eight milliliters at a time.

So it's like two teaspoons full or something.

Yeah.

I mean, it's an extremely tiny amount.

And it's very labor-intensive process, very expensive process.

I mean, one syringe that is being injected into people, this eight milliliters of red blood cells, not counting all the decades of R D that went into it, roughly $75,000 per syringe.

Oh my gosh.

Yeah.

Whereas, you know, the American Red Cross is charging like 200, 250 bucks for a pint.

So it's not competitive.

It's not at scale.

It is definitely early stage.

On the other hand, as I saw in the UK, the world's first trial to inject lab-grown blood into healthy humans is underway at the moment, and they seem to be fine.

That seems like very different from the rabbits, then.

Yeah, it's going into healthy humans.

And what was, I mean, you saw what happened with the rabbits.

They kind of got their mojo back.

What happens when it gets injected into humans?

Well, so it's a randomized trial.

So I was blinded, as were the participants.

So I cannot say what was being injected into the volunteer that I saw, but I will say that he was so excited about the whole thing that his blood pressure went through the roof and all the machines were beeping and the nurses were freaking out.

And it was like, oh, God.

It felt like those scenes on like TV shows where suddenly it's like, crash.

Yeah, yeah, yeah.

But actually, he was just very excited because this trial has been so long in the works.

And I spoke to one of the participants who has had both his injections.

So he's definitely had the artificial blood.

And it's, I mean, it's, there have been no side effects at all.

And that's no side effects in the moment and then no side effects down the line?

Yeah, they're testing it for 120 days out and they're testing for two things.

So they're looking for, is there a transfusion reaction, which is a, that's your body saying, I don't want this.

That isn't happening.

The other thing they're looking for is: how long do those synthetic red blood cells survive in the body?

The hope is that they will survive for longer than a natural red blood cell because they are brand new when they go in.

Whereas the control is just normal donor-derived blood, some of that is old.

Some of it is already at the end of its life.

And so, the hope is that this synthetic blood will actually be lasting longer than the normal stuff in people's body.

What is your feeling of optimism or pessimism here?

It seems like there's reason to be skeptical, to pump the brakes here, especially because of this history of deadly studies.

It feels like at the same time, though, there are two different optimistic paths forward.

Neither seems close to a guarantee.

But

I don't know.

Do you feel hopeful about about this research?

Yeah, at first, I was very skeptical.

And having reported on lab-grown meat as a journalist, I was like, what?

There's just no way economically that this could ever compete with something that people give freely from their arms and can just make without even thinking about it.

I was just like, not a chance.

There is literally no way that growing red blood cells in a lab can be scaled up without pharma-style money.

But what's interesting is that's the direction they're going because it turns out that if you can grow red blood cells in a lab, well, you can grow red blood cells that also have an enzyme in them that pumps out a drug that will circulate around your body without triggering your immune system because it's sheathed in a red blood cell.

And so it opens up a whole pathway to next generation therapeutics that are going to be completely different from the kind of drugs we have right now and potentially much more effective.

Like beyond blood.

Exactly, exactly.

I'm almost thinking like how COVID vaccines opened this whole new world of mRNA vaccines in general.

And now we're getting these mRNA vaccines for cancer and things like that.

The researchers I spoke to literally used the mRNA analogy.

Like that's how they're seeing this.

I think, you know, I went in the skeptic.

I came out thinking, well, this is not going to be saving your life anytime soon.

Yeah.

But might down the line actually get there.

And in the process of getting there, I think it's going to bring us a lot of really

kind of amazing treatments, as well as advances in understanding of how our blood actually does all the great things it does.

There are real benefits to trying to do this and failing.

And I feel like, you know, you also fail better each time.

That was Nicola Twilley.

She wrote about blood for the New Yorker.

And if you want to hear more from her, you can check out her podcast, Gastropod, which looks at food through the lens of science and history.

Or you can read her latest book.

It's called Frostbite: How Refrigeration Changed Our Food, Our Planet, and Ourselves.

This episode was produced by me, Noam Hasenfeld.

We had editing from Jorge Just, mixing and sound design from Christian Ayala, music from me, production support from Thomas Liu, and fact-checking from Melissa Hirsch.

Meredith Hodnott runs the show, Julia Longoria's got plastic on the brain, and Bird Pinkerton picked up the note off the control panel at the octopus hospital.

If you ever want to see the doctopus again, it said,

I challenge you to a duel.

At the bottom, there was a signature:

Aaron Bird.

Thanks as always to Brian Resnick for co-creating the show.

And if you have thoughts about the show, send us an email.

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