
Tens of thousands of lives could be saved each year if hospitals had more blood.
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Adrian
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Noam Hassenfeld
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Noam Hassenfeld
I'm Noam Hassenfeld 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.
Nikki Twilley
Putting fish in the fridge. Great. On day one, day five, not as great.
Noam Hassenfeld
We can't reproduce it.
Nikki Twilley
That's still not a reality.
Noam Hassenfeld
And we just can't get enough people to donate it.
Nikki Twilley
Roughly 40% of Americans are eligible to donate. Fewer than 3% actually do.
Noam Hassenfeld
That's Nikki Twilley. She's a science writer who just wrote.
Adrian
This great New Yorker piece, All about blood.
Noam Hassenfeld
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.
Nikki Twilley
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.
Noam Hassenfeld
One study estimated that one in three people who died from bleeding due to injury could have been saved if we.
Alan Doctor
Just had more blood.
Noam Hassenfeld
But what if we didn't need to be like vampires sucking blood out of people in just the right way in.
Adrian
Order to keep ourselves alive?
Noam Hassenfeld
What if we could just make it ourselves?
Nikki Twilley
How hard can it be?
Adrian
So, Nikki, the first thing that hit.
Alan Doctor
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.
Nikki Twilley
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 said sort of thought of it like a liquid, like milk, you know, 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.
Alan Doctor
And if you were to just run through the kind of basic stuff that blood does, what are the greatest hits?
Nikki Twilley
Okay, so the biggest and most important is picking up oxygen in the lungs and releasing it around the body.
Alan Doctor
Okay.
Nikki Twilley
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.
Alan Doctor
Is that why replicating blood is so hard? Just because it does so many different kinds of things?
Nikki Twilley
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.
Noam Hassenfeld
Okay, so how are scientists trying to make this actually happen?
Nikki Twilley
So I focused on two kind 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 Dr.
Alan Doctor
Incredible.
Nikki Twilley
But he, he is leading a $46 million DARPA funded initiative to make entirely artificial blood from scratch. Okay, 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.
Alan Doctor
So how is he approaching this research? What's his strategy to make artificial blood?
Nikki Twilley
It's a really interesting project that he sort of got into by accident.
Alan Doctor
Okay.
Nikki Twilley
His colleague was working on synthesizing nanoparticles for MRI imaging and was like, huh, looks like a red blood cell.
Noam Hassenfeld
So Dr. Alan Docter's colleague.
Nikki Twilley
Yep.
Noam Hassenfeld
Just had this particle that coincidentally looked like a red blood cell.
Nikki Twilley
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 Allen Dr. 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.
Noam Hassenfeld
And so just because it looks like.
Alan Doctor
A red blood cell isn't supposed to do the function of a red blood cell.
Nikki Twilley
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.
Alan Doctor
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.
Nikki Twilley
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.
Noam Hassenfeld
So how well does it work?
Nikki Twilley
Well, I mean, when I was there, they were testing it on rabbits. And I mean, the 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 60ml 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. That is 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.
Alan Doctor
Yeah.
Noam Hassenfeld
Have we ever gotten to this kind of research place before and then it didn't end up working out?
Nikki Twilley
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 hbox.
Noam Hassenfeld
Hbox?
Nikki Twilley
Hemoglobin based oxygen carriers.
Alan Doctor
Oh, it's an acronym. Okay.
Nikki Twilley
Yeah. And there was a big push for these that was actually motivated primarily by the AIDS crisis. So the first AIDS case was in 1981. There wasn't a way to test blood for HIV until 1985.
Alan Doctor
Wow.
Nikki Twilley
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?
Adrian
Yeah, what could go wrong?
Nikki Twilley
Well, 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 US history. 52 patients got the product, 24 died, compared to only 8 of the control patients. So it was actually shut down.
Alan Doctor
Sorry. You said 52 patients and 24 died.
Nikki Twilley
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.
Adrian
Yeah.
Alan Doctor
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.
Nikki Twilley
Exactly. I mean, I love a good bet, you know, and 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.
Alan Doctor
Yeah. Is there another way other than making fully artificial blood to solve this crisis?
Nikki Twilley
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.
Adrian
Coming up in a minute. How to grow blood. Support for the show comes from Roomba robots. I got a lot of things on my to do list. Laundry, groceries, dishes, recording ads. Something's always getting put off. But with a Roomba robot, one thing you don't have to put off is cleaning your floors. IRobot says their brand new Roomba Plus 405 combo can vacuum, mop, and even do both at the same time. It can vacuum first and then apparently retrace its steps and mop the area it vacuumed earlier. Except it can't really retrace its steps because it doesn't have feet. Can you imagine it uses advanced spinning dual clean mop pads to help your floors shine. And iRobot says it can even empty itself automatically and wash its own mop pads, all without you having to get anywhere near your to do list.
Noam Hassenfeld
You can even give your Roomba robot.
Adrian
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Alan Doctor
Doctor, Doctor, give me the news.
Noam Hassenfeld
I got a vacation. Unexpected 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.
Nikki Twilley
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 this 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.
Alan Doctor
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.
Nikki Twilley
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. You don't even have to understand how it. We just have to understand how to make it want to become a red blood cell. 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 8ml at a time. So it's like 2 teaspoons full or something. Yeah, I mean it's an extreme, extremely tiny amount and it's very labor intensive process, very expensive process. I mean one syringe that is being injected into people, this 8 milliliters of red blood cells, not counting all the decades of R and D that went into it, roughly $75,000 per syringe.
Alan Doctor
Oh my God.
Nikki Twilley
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.
Alan Doctor
That seems like very different from the rabbits then.
Nikki Twilley
Yeah, it's going into healthy humans.
Alan Doctor
And what was, I mean you saw what happened with the rabbits. They kind of got their mojo back. What happens when it, when it gets injected into humans?
Nikki Twilley
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 o, oh God. It felt like those scenes on like TV shows where suddenly it's like crash.
Alan Doctor
Yeah, yeah, yeah.
Nikki Twilley
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.
Alan Doctor
And that's no side effects in the moment and then no side effects down the line.
Nikki Twilley
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. 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.
Alan Doctor
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 this research?
Nikki Twilley
Yeah, at first I was very skeptical and having reported on lab grown meat as a journalist, I was like, well, 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's 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 labor 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. Cause 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.
Noam Hassenfeld
Like beyond blood, right?
Nikki Twilley
Exactly, exactly.
Alan Doctor
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.
Nikki Twilley
The researchers that I spoke to literally used the MRNA analogy. Like that's how they're seeing this.
Alan Doctor
Okay.
Nikki Twilley
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 it 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.
Noam Hassenfeld
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 How Refrigeration Changed Our Food, Our Planet, and Ourselves. This episode was produced by me, Noam Hassenfeld. 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 Hodinot runs the show, Julia Longoria's got Plastic on the Brain and Bird Pinkerton picked up the note off the.
Alan Doctor
Control panel at the Octopus Hospital if.
Noam Hassenfeld
You ever want to see the Doctopus again.
Alan Doctor
It said, I challenge you to a duel. At the bottom there was a signature Aaron Bird.
Noam Hassenfeld
Thanks as always to Brian Resnik for co creating the show and if you have thoughts about the show, send us an email. We're@ unexplainableox.com and you can also leave us a review or a rating wherever you listen. It really helps us find new listeners. You can also support this show and all of Vox's journalism by joining our membership program today. You can go to vox.commembers to sign up. If you do, you'll be helping make this place run, but you'll also get unlimited access to all of the reporting on Vox.com, you'll get exclusive newsletters, and you'll get all of our podcasts ad free. Think about it. Unexplainable is part of the Vox Media Podcast Network and we'll be back next week.
Adrian
Support for the show comes from Roomba Robots. A lot of people are talking about robots.
Noam Hassenfeld
Aren't they going to take our jobs? Are they going to take over the world?
Adrian
Not enough people are talking about our floors because the robots have already done it. They've figured out a way to clean floors all on their own and it's kind of great. Roomba robots work so well because they use a four stage cleaning system and Clearview lidar to navigate your home. Lidar. They aren't messing around. Roomba robots were made for this. Learn more@irobot.com that's I r o b o t dot com.
Unexplainable: The Real Quest for Fake Blood
Episode Release Date: April 23, 2025
Introduction: The Unsung Hero of Blood Donation
The episode opens with Noam Hassenfeld recounting the remarkable story of James Harrison, an 88-year-old who quietly saved nearly two and a half million lives through his extraordinary blood donations. Harrison, a humble railway clerk, possessed a rare antibody in his blood that was pivotal in creating a medication saving countless babies worldwide. Despite his fear of needles and the demanding schedule of over 1,200 donations spanning 64 years, Harrison's unwavering commitment underscores the critical yet often overlooked role of blood donors.
Understanding the Complexity of Blood
Nikki Twilley, a science writer, delves into the multifaceted nature of blood, highlighting its crucial roles:
Twilley emphasizes, "Blood is alive. It's filled with cells that are doing things, and it's very hard to keep it alive outside the body" [03:56]. This complexity makes replicating blood a formidable scientific challenge.
The Quest for Synthetic Blood
The discussion shifts to contemporary efforts to create artificial blood. Dr. Alan Doctor, leading a $46 million DARPA-funded initiative, is at the forefront of this research. Twilley explains Dr. Doctor’s innovative approach to synthesizing red blood cells:
"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" [07:04]. The challenge lies in replicating the dynamic nature of hemoglobin, which in the body is aided by enzymes to release oxygen effectively. Despite the ingenuity of Dr. Doctor's method, replicating this biological process synthetically remains elusive.
Historical Hurdles: The Hbox Failures
Twilley recounts the history of synthetic blood development, highlighting the notorious Hbox (Hemoglobin-Based Oxygen Carriers) trials during the AIDS crisis:
"They were on the verge of success... but it was a complete flop. People were like, ‘I guess we really can't make a synthetic blood. It's too complicated for us’" [11:34]. One such trial by Baxter Pharmaceuticals resulted in a tragic outcome where 24 out of 52 patients died, leading to the project's termination by the FDA [12:15]. This failure cast a long shadow over the field, illustrating the profound risks and complexities involved in creating safe synthetic blood alternatives.
Lab-Grown Blood: A Promising Avenue
Shifting focus, Twilley explores the burgeoning field of lab-grown blood, which leverages human embryonic stem cells to cultivate red blood cells in controlled environments.
"Once you tell the stem cell that it wants to be a red blood cell, it knows how to do oxygen delivery" [18:03]. Despite the potential, current production methods are prohibitively expensive and yield minimal quantities—only about 8ml per culture at a staggering cost of $75,000 per syringe [19:10]. However, the UK's National Health Service has initiated trials injecting lab-grown blood into healthy humans, showing promising early results with no immediate side effects [19:38].
Current Trials and Future Prospects
In the UK trials, participants have received lab-grown blood with encouraging outcomes. Twilley observes, "There have been no side effects at all" [20:38], though rigorous long-term studies are ongoing to evaluate the longevity and compatibility of these synthetic cells within the human body.
Dr. Doctor reflects on the potential impacts, comparing the innovation to the revolutionary advances seen with mRNA vaccines:
"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... it might down the line actually get there" [22:59]. The research hints at broader therapeutic applications, such as delivering drugs within red blood cells without triggering immune responses, potentially transforming future medical treatments.
Conclusion: A Balance of Skepticism and Hope
The episode culminates with a nuanced perspective on the future of synthetic and lab-grown blood. While acknowledging the significant hurdles and historical setbacks, Twilley remains cautiously optimistic about the long-term benefits and scientific advancements spurred by this research:
"I fully believe humans can get there one day, but it's a complicated project" [13:31]. The ongoing efforts not only aim to solve the immediate crisis of blood shortages but also pave the way for groundbreaking medical therapies beyond the realm of transfusions.
Key Takeaways:
This episode of Unexplainable meticulously unpacks the intricate journey towards creating artificial blood, blending human stories with scientific exploration to illuminate a quest that bridges the known and the unknown.
Notable Quotes:
Credits: Produced by Noam Hassenfeld with contributions from Nikki Twilley and Alan Doctor. Special thanks to the Unexplainable team: Jorge (editing), Christian Ayala (sound design), Thomas Liu (production support), and Melissa Hirsch (fact-checking).