Blood farm

Tens of thousands of lives could be saved each year if hospitals had more blood. So scientists are racing to understand how this living fluid does what it does in order to one day grow it from scratch. Guest: Nicola Twilley, New Yorker contributor and host of Gastropod. For show transcripts, go to vox.com/unxtranscripts For more, go to vox.com/unexplainable And please email us! [email protected] We read every email. Support Unexplainable (and get ad-free episodes) by becoming a Vox Member today: vox.com/members Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:01Noam Hassenfeld?

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• 0:38Noam Hassenfeld?

  It's Unexplainable. I'm Noam Hassenfeld. And a couple of 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 2.5 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.

• 1:19Noam Hassenfeld?

  But the part of the story I keep coming back to is that James had to keep donating his blood, almost 1,200 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.

• 1:50Noam Hassenfeld?

  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.

• 2:02Speaker 01

  It's like putting fish in the fridge. Great on day one. Day five, not as great.

• 2:08Noam Hassenfeld?

  We can't reproduce it.

• 2:09Speaker 01

  That's still not a reality.

• 2:11Noam Hassenfeld?

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

• 2:14Speaker 01

  Roughly 40% of Americans are eligible to donate. Fewer than 3% actually do.

• 2:20Noam Hassenfeld?

  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.

• 2:36Speaker 01

  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.

• 2:50Noam Hassenfeld?

  One study estimated that 1 in 3 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?

• 3:12Speaker 01

  How hard can it be?

• 3:19Noam Hassenfeld?

  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.

• 3:39Speaker 01

  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?

• 3:56Noam Hassenfeld?

  Yeah.

• 3:56Speaker 01

  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.

• 4:06Noam Hassenfeld?

  And if you were to just run through the kind of basic stuff that blood does, what are the, what are the greatest hits?

• 4:15Speaker 01

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

• 4:23Noam Hassenfeld?

  Okay.

• 4:24Speaker 01

  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.

• 4:37Noam Hassenfeld?

  Hmm.

• 4:38Speaker 01

  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.

• 5:06Noam Hassenfeld?

  Is that why replicating blood is so hard? Just because it does so many different kinds of things?

• 5:13Speaker 01

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

• 5:18Noam Hassenfeld?

  Okay.

• 5:19Speaker 01

  Two challenges there.

• 5:22Noam Hassenfeld?

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

• 5:28Speaker 01

  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.

• 5:40Noam Hassenfeld?

  Okay.

• 5:41Speaker 01

  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 Doctor Doctor, his name is Alan Doctor.

• 5:57Noam Hassenfeld?

  Incredible.

• 5:58Speaker 01

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

• 6:09Noam Hassenfeld?

  Okay.

• 6:10Speaker 01

  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.

• 6:19Noam Hassenfeld?

  So how is he approaching this research? What's his strategy to make artificial blood?

• 6:24Speaker 01

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

• 6:29Noam Hassenfeld?

  Okay.

• 6:29Speaker 01

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

• 6:39Noam Hassenfeld?

  So Dr. Alan Docter's colleague?

• 6:42Speaker 01

  Yep.

• 6:43Noam Hassenfeld?

  Just had this particle that coincidentally looked like a red blood cell?

• 6:47Speaker 01

  Exactly. It was a total accident and he ended up calling Alan Docter, who had been interested in blood because it was this issue in his medical practice. And immediately Alan Docter 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.

• 7:12Noam Hassenfeld?

  And so just because it looks like a red blood cell, it's supposed to do the function of a red blood cell?

• 7:18Speaker 01

  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.

• 7:41Noam Hassenfeld?

  Hmm.

• 7:42Speaker 01

  But in our bodies, there's a sort of molecule that, that makes sure the hemoglobin can change shape slightly and that forces it to let go of its oxygen.

• 7:55Noam Hassenfeld?

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

• 8:08Speaker 01

  Well, I mean, I said to Dr. Docter, 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.

• 8:28Noam Hassenfeld?

  So how well does it work?

• 8:30Speaker 01

  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, 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.

• 9:14Speaker 01

  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.

• 9:40Speaker 01

  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.

• 10:03Noam Hassenfeld?

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

• 10:09Speaker 01

  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.

• 10:24Noam Hassenfeld?

  H-Box?

• 10:25Speaker 01

  Hemoglobin-based oxygen carriers.

• 10:27Noam Hassenfeld?

  Oh, it's an acronym, okay.

• 10:28Speaker 01

  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.

• 10:43Noam Hassenfeld?

  Wow.

• 10:44Speaker 01

  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?

• 11:17Noam Hassenfeld?

  Yeah, what could go wrong?

• 11:20Speaker 01

  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.

• 11:49Noam Hassenfeld?

  Whoa.

• 11:49Speaker 01

  Fifty-two patients got the product, 24 died.

• 11:53Noam Hassenfeld?

  Whoa.

• 11:53Speaker 01

  Compared to only eight of the control patients, so.

• 11:56Noam Hassenfeld?

  Oh, man.

• 11:57Speaker 01

  It was actually shut down.

• 11:58Noam Hassenfeld?

  Sorry, you said 52 patients and 24 died?

• 12:02Speaker 01

  Yeah.

• 12:02Noam Hassenfeld?

  Wow.

• 12:03Speaker 01

  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.

• 12:36Noam Hassenfeld?

  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.

• 12:50Speaker 01

  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.

• 13:14Noam Hassenfeld?

  Yeah. Is there another way other than making fully artificial blood to solve this crisis?

• 13:23Speaker 01

  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.

• 13:39Noam Hassenfeld?

  Coming up in a minute, how to grow blood.

• 13:46Speaker 02

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• 15:21Noam Hassenfeld?

  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's 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.

• 16:06Noam Hassenfeld?

  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.

• 16:33Speaker 01

  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.

• 17:18Speaker 01

  What you need to do is figure out what are the Those chemical cues 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's 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.

• 17:52Noam Hassenfeld?

  And I, you know, I, 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.

• 18:00Speaker 01

  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.

• 18:17Noam Hassenfeld?

  Interesting.

• 18:17Speaker 01

  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.

• 18:46Noam Hassenfeld?

  Yeah.

• 18:46Speaker 01

  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 and D that went into it, roughly $75,000 per syringe.

• 19:07Noam Hassenfeld?

  Oh, my God.

• 19:08Speaker 01

  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.

• 19:30Speaker 01

  Is underway at the moment. And they seem to be fine.

• 19:35Noam Hassenfeld?

  That seems like very different from the rabbits, then.

• 19:38Speaker 01

  Yeah, it's going into healthy humans.

• 19:40Noam Hassenfeld?

  And what was, I mean, you saw what happened with the rabbits. They they kind of got their mojo back. What happens when it when it gets injected into humans?

• 19:47Speaker 01

  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.

• 20:17Noam Hassenfeld?

  Yeah, yeah, yeah.

• 20:18Speaker 01

  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.

• 20:36Noam Hassenfeld?

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

• 20:39Speaker 01

  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.

• 21:25Noam Hassenfeld?

  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?

• 21:53Speaker 01

  Yeah, 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 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

• 22:37Speaker 01

  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.

• 22:56Noam Hassenfeld?

  Like beyond blood?

• 22:57Speaker 01

  Exactly, exactly.

• 22:59Noam Hassenfeld?

  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.

• 23:09Speaker 01

  The researchers that I spoke to literally used the mRNA analogy. Like, that's how they're seeing this.

• 23:15Noam Hassenfeld?

  Okay.

• 23:15Speaker 01

  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.

• 23:21Noam Hassenfeld?

  Yeah.

• 23:21Speaker 01

  But it might, down the line, actually get there.

• 23:26Speaker 01

  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.

• 23:56Noam 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 Frostbite: 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 Lu, and fact checking from Melissa Hirsch. Meredith Hadnot runs the show, Julia Langoria's got plastic on the brain, and Bird Pinkerton picked up the note off the control panel at the octopus hospital.

• 24:37Speaker 03

  If you ever want to see the doctopus again,

• 24:39Noam Hassenfeld?

  it said.

• 24:41Speaker 03

  I challenge you to a duel.

• 24:43Noam Hassenfeld?

  At the bottom, there was a signature.

• 24:47Speaker 03

  Aaron Bird.

• 24:52Noam Hassenfeld?

  Thanks, as always, to Brian Resnick for co-creating the show. And if you have thoughts about the show, send us an email. We're at [email protected]. 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.com/members 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.

• 25:43Speaker 04

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