Life-saving advancements have come a long way, but engineering artificial blood has been a challenge. Nicola Twilley is a New Yorker contributor and co-host of the podcast Gastropod. She talks to Krys Boyd about the breakthroughs — and setbacks — in the quest for artificial blood, why it’s needed more than ever, and why eyes are on Big Pharma to finance it. Her article is “The Long Quest for Artificial Blood.”
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Transcript
Krys Boyd [00:00:00] The 1960 horror film psycho was shot in black and white because Alfred Hitchcock didn’t need the fake blood to be red. He found he could get the exact sort of stickiness and opacity he was looking for by using watered down chocolate sirup. Soon after, filmmakers perfected artificial blood for Technicolor, but 65 years later, scientists are still tinkering with blood substitutes for trauma patients. From KERA in Dallas, this is Think. I’m Krys Boyd. For now, the best known therapy for someone who has lost a lot of blood is blood from a human donor. Transfusion procedures have saved millions of lives. But as my guest will tell us, they’ve never been a perfect solution. Not least because there isn’t always enough donor blood available when and where it’s needed. Nicola Twilley is co-host of the podcast Gastropod and a contributor at The New Yorker, which published her article “The Long Quest for Artificial Blood.” Niki, welcome back to Think.
Nicola Twilley [00:00:57] Thanks so much for having me.
Krys Boyd [00:00:59] You open this piece with two simultaneous blood experiments, one on a human man in the UK, the other on rabbits in Baltimore. What were the substances being tested on these subjects?
Nicola Twilley [00:01:12] Well, they were both artificial blood in a way, but in different ways. So I thought of them as like the Impossible Burger and the lab grown burger of blood. It’s a little bit of a gory idea, but one was synthetic blood that does the same thing as it as real blood. So that’s the Impossible Burger. And then the other was blood that had been grown in a lab and was being injected into the human man in the UK. So two different approaches to cracking the same problem.
Krys Boyd [00:01:47] How does one go about growing human blood in a lab outside of a human body?
Nicola Twilley [00:01:54] Yeah, surprisingly difficult actually. Or maybe not that surprising, I don’t know, but our bodies make a lot of this stuff. They’re making millions of red blood cells every minute. And yet recreating it in a lab turns out to be a really recent breakthrough. And something that we can do only at the tiniest of scales. So the the two teaspoons full of blood that I saw being injected into this person had taken three weeks to grow, but had taken two decades to be able to grow that much. The short version is what you do is you isolate stem cells from a blood donation. These are stem cells that have already decided they want to be blood, but they haven’t decided what kind of blood cells. But they haven’t decided if they want to be a platelet or a white blood cell or red blood cell. And then what you do is you basically you isolate them and you treat them the right way to get them to decide to become a red blood cells. That involves feeding them the right thing at the right time, keeping them at the right temperature, you know, isolating, purifying. There’s a whole regime to just basically convince them to grow up and reproduce into red blood cells.
Krys Boyd [00:03:09] So it’s good to know that the two teaspoons, a syringe of this did not give the human subject a seizure or something. But how can scientists know what happens to those manufactured blood cells over time in his body?
Nicola Twilley [00:03:23] Yeah, this is the interesting bit because you you put it in there and you, you hope that everything’s all right. But what scientists also want to know is that the body doesn’t just get rid of it straight away as an alien kind of thing. So what they do is they tag it with radioactive particles, and it’s about the same dose of radioactivity is going on vacation in Cornwall. So really not very much, but enough that when nurses go and draw blood from this, this volunteer who basically turns into a human pincushion, They go and draw blood, you know, on day one, on day three, on day five, on day seven, on day nine. They keep doing that for six months. And what they can, they can tell from the level of radioactivity and what they draw is how long those lab grown blood cells have lasted inside the person.
Krys Boyd [00:04:17] So the substance that the rabbits received, this was the blood substitute. So tell us a little bit more about that.
Nicola Twilley [00:04:24] Yeah. This is an entirely synthetic version of red blood cells. So it does the same thing. It carries oxygen around the body but it does it, you know, with something that’s made of lipids in a lab. So what that is primarily is hemoglobin extracted actually from expired donor blood. So that’s the particle that picks up oxygen in our own red blood cells. You could get it from other places. This is just the most convenient place to get it from. Now. It’s an iron rich protein. It’s the reason our our blood is red. Actually, that iron gives it that red color. And what they do is they encapsulate that hemoglobin in a nanoparticles. So this is very, very, very tiny, you know, a miniature a 50th the size of an actual red blood cell, which is already pretty tiny. And it they make, you know, this is this is material science. They make a, a sort of an artificial membrane for it are real red blood cells have membranes too, that our body makes. This is just one made in a lab from various molecules, a lot of lipids. There’s some cholesterol in there, interestingly enough, because cholesterol is sort of stiff enough to hold it together. I guess how it stiffens up your arteries too. But they make this artificial kind of case for it. And, and that’s how this synthetic red blood cell works. And then because it’s synthetic, they can tweak it in various ways. So they do that so that it can pick up more oxygen in your, your lungs and let more go in your muscles. It’s almost like a performance enhancing drug. It gives you the effect as if you had been training at altitude without actually doing that.
Krys Boyd [00:06:18] You’ve touched on a couple of these already, but will you just tell us some of the things that real natural blood does in an animal’s body, a helix, specifically a human’s body?
Nicola Twilley [00:06:30] Yeah. I mean, blood turns out to be pretty miraculous. I had not really realized this. I think, you know, I just thought of it as just another bodily fluid, but it is responsible for carrying oxygen around our bodies. That’s the sort of biggest thing, because without that, we die within, you know, a minute or so. But it’s also delivering nutrients. It’s transporting hormones. It is taking out the trash. So it sort of carts away a lot of toxic waste products from our bodily processes carbon dioxide, urea, lactic acid. It is responsible for regulating body temperature for our overall chemical and fluid balance. So hydration, that’s what blood is in charge of monitoring. It also is on the defense raising the alarm for any organ damage and any immune system threats. So anything that’s alien that our body needs to respond to or any wounds that need to be healed, blood is constantly patrolling, looking for those and mobilizing to deal with them. So it’s kind of a huge array of the things that keep us alive. Blood turns out to be responsible for.
Krys Boyd [00:07:48] You’ve learned that humans have always had a sense of blood is a kind of sacred substance. I mean, we surely always understood that if we lost enough of it, we wouldn’t be able to survive. How did people tend to talk and write about blood, though? Before modern science could tell us why it was such an amazing substance?
Nicola Twilley [00:08:07] People always had a sense of it being sort of this essential element, really, and essential in the sense that it was also really your soul. So you have expressions like blood brothers or a blood oath. People understood that that blood really meant something, that it was sort of at the essence of what it was to be human and to be alive. And that’s why blood is also what was sacrificed to gods. You know, in the in communion, you know, Christians drink wine to remind them of the blood that was given for them. So it’s it’s always had this very deep meaning and a sense also of like this is this is where the true essence of your personality resides to. So even before anyone understood all the mechanical things the blood does, there was a sense that if you if your blood was imbalanced or somehow out of humor, then your personality was too. Which is why bloodletting was such a popular treatment before modern modern medicine was the sense that, you know, if you could let some out of the bad stuff, that would put you back in balance. It’s sort of the opposite approach to what we take today, where we give people blood transfusions. But there’s an equal sense that blood is essential.
Krys Boyd [00:09:29] Before we get more into the relative pros and cons of artificial versus lab grown blood, we should talk about why we need either one. Why is donor blood not sufficient to meet the needs of every patient who can benefit from it?
Nicola Twilley [00:09:43] Right. Well, so blood, I’ve just spent all this time saying why it’s amazing, but it does have some downsides for people who want to give it to patients who need it. So one of the things is it can be disease. And one of the earliest sort of impetuses to artificial blood development was actually from HIV Aids. There was, you know, a sort of five year gap between the first Aids case and an effective test for whether blood was carrying HIV or not. And that sort of drove people into a panic because any transfusion could have infected someone with HIV. And that really gave an impetus to artificial blood research. So that’s always an issue with blood. It can carry disease. It also for in most cases isn’t universal. Even universal donor blood will have slight variations. So removing the removing the sort of blood typing of it would make it more universal. And in situations where you don’t have time to type it, that would be great. And then there’s the issue of the fact that it’s actually kind of hard to keep alive outside of the body. Again, I had thought a blood is just this fluid, but in some ways it’s more like an organ, in that when you take it out of the body, you have to do quite a lot to keep it alive, and it will die outside the body. So you, you platelets, for example, which are the component in blood, the one that’s responsible for clotting. They have like a five day shelf life. And they have to be constantly jiggled to stay alive. So you can imagine that that makes them a little difficult to store and a little difficult to get to people who are like, not in a major trauma hospital. So that’s one issue. Then, as I said, they have a short shelf life, so they expire red blood cells, for example. They only last for 42 days. By that time before they’ve expired, they’ve already lost 40% of their oxygen carrying capacity. So the researcher I spoke to compared it to fish, right. You can keep fish in the refrigerator for five days. It’s just not getting any better. Blood’s like that too. And then there’s the issue of the fact that we just don’t have enough. Not enough people are donating blood. And so you get situations which scientists I spoke to told me about where you can be. For example, this was the example was New Orleans, where on a Tuesday morning there just were no platelets. There just weren’t any like they didn’t have any in house. And so that’s very rare. You know, the American Red cross aims to keep, you know, five days supply on hand ideally seven. But it’s always on a knife edge. You get these sort of blood crises and that’s because people aren’t giving enough blood. I think it was, you know, the sort of an estimate of needing something ridiculous, like 60,000 to 100,000 more donations each year to get to an adequate amount. So, yeah, it’s I mean, of the 38% of Americans who are eligible to donate, fewer than 3% actually do. So yeah, that’s the real issue.
Krys Boyd [00:13:05] Why don’t people donate blood if they can?
Nicola Twilley [00:13:08] You know, it’s a great question. And if I had the answer, I would probably be head of some task force to fix it. But I will say that I think people don’t understand how necessary it is. And I think for me at least, part of the problem is in the U.S., you you donate voluntarily. But then the American Red cross sells it, and they say they’re only covering their costs. And, you know, that’s that’s reasonable. But it seems sort of like, wow, that’s a business built on my voluntary donation. I think people think it’s going to hurt. I think people don’t have time. It takes 20 minutes. I, you know, people don’t think it’s going to happen to them. Even though needing blood is such a common phenomenon and particularly among young people. I don’t know, I think there’s a lot of reasons.
Krys Boyd [00:13:59] Nicola, to go back to what you were just talking about. Humans donate their blood. The blood then gets sold in the United States. What are the economics around that? Like? Is there a retail price of a pint of whole blood suitable for transfusion?
Nicola Twilley [00:14:13] There is. And this is something the American Red cross is little cagey on, but it’s between 200 and 250 bucks a unit as a general rule.
Krys Boyd [00:14:24] And why is it legal in the U.S. to pay donors for plasma, which is part of blood, but illegal to pay them for a pint of whole blood?
Nicola Twilley [00:14:32] Yeah, that has an interesting history. It used to be legal to pay them for whole blood, and it had this sort of predictable effect of attracting folks who really needed the money, and that is seen as a recipe for a unsafe blood supply. You know, folks who are maybe drug addicts or alcoholics who might be more likely to have hepatitis or have been infected with hepatitis and not have tested positive for it yet, for example, are the kind of people who, in a system where you get paid for your donation, might be motivated to donate and then put the whole blood supply in danger. So there was a whole sort of scandal around this. They called it booze for ous, because people were giving their blood and then taking the money and, and spending on alcohol, on booze and hence sort of the, the crackdown on that and banning that. Why plasma is allowed is, is because it’s a longer process actually. And you just wouldn’t get people volunteering to do it. But it’s also seen as a sort of slightly sordid and extractive industry. And a lot of people who do do it are doing it because they need the money. So those might be students, but they also might be people who have lifestyles where they are potentially exposed to some risk in general. The World Health Organization recommends voluntary donations for the reasons of safety. It’s a tough call because we don’t have enough from a voluntary donation, and the only times we’ve had honestly have been, for example, World War II, where the American Red cross really motivated people around. You know, on the home front, this was your way to support the troops. But it seems kind of hard to to get people motivated the rest of the time. Certainly they haven’t been successful.
Krys Boyd [00:16:32] So we don’t often have enough from voluntary donations. Blood is perishable the moment it leaves a person’s body. Can it be preserved by freezing?
Nicola Twilley [00:16:43] Yes. You can freeze red blood cells, for example. Unfortunately, you then have to defrost them, which you do. You know, they’re delicate, they’re alive. You have to do that pretty tenderly, as a, as it were. And then you also have to wash them again, quite tenderly, to get rid of the antifreeze you put in. But the whole point about blood is when you need it, you need it every single minute of every single minute of delay. And replacing lost blood increases mortality by 5%. So waiting to defrost red blood cells and then washing out the antifreeze sort of negates the purpose. Unfortunately, they do do it, especially for super rare blood types of someone say who has sickle cell disease and needs it, needs regular transfusions and you might not have their blood type on hand. They will keep frozen reserves for that, but it’s not a great solution for just regular. I am having postpartum hemorrhage, or I’ve been in a car crash and I need blood or any of those situations where it’s a matter of urgency. Now plasma can be frozen and actually can be freeze dried. And so that piece that’s in plasma is another component of blood. It’s it’s sort of there to really make up volume in a lot of ways, although it’s also carrying a lot of important elements of blood that can be frozen. But red blood cells and platelets cannot.
Krys Boyd [00:18:16] So aside from the problem of availability, of course, you know, it’s easy to overlook how remarkable it is that transfusions can work in modern medicine. When did doctors first start to experiment with the idea of something like a transfusion?
Nicola Twilley [00:18:36] Well, as soon as they realized in the 1660s that the heart was pumping this blood stuff around the body. People were like. This is a really interesting concept. So what had happened was the Catholic Church relaxed its prohibition on dissecting humans for anatomical research, and a whole stream of discoveries came out of that. And one of those was by a British doctor called William Harvey, who figured out that the heart was pumping blood around the body. And straight away people were like, I wonder now that we understand this is the liquid going around the body, what would happen if we added other things to that liquid? And maybe that would impart some of those sort of essences of these other liquids into the human. And so Christopher Wren, who is better known for being the architect behind Saint Paul’s Cathedral in London, he did some of the first transfusions, actually infusing dogs with alcohol, with opium, with various powerful liquids. Antimony, which was sort of a powerful liquid in alcohol. Alchemical thought. So he tried all of these things, thinking that maybe something would happen. And a lot of the early doctors also thought that, remember I said that, you know, people thought the essence of a human was in their blood. Well, what if you transfused blood from a happy person into a sad person? Would you cheer this sad person up? People thought that maybe if husbands and wives weren’t getting along, you could just transfuse their blood and they would sort of achieve a mind meld, as it were, a blood meld. People thought you could transfuse the blood of old people into young people. So there were a lot of ideas. As soon as people realized blood was a liquid, you know, pumping around the body. And you, you could add things to it. Doctors were like, well, hey, let’s get going with this.
Krys Boyd [00:20:37] When donor blood started to be transfused to compensate for excessive blood lost in childbirth, some of those transfusions, I guess, were totally successful. And some of them were catastrophic. And for a while, nobody could figure out why.
Nicola Twilley [00:20:52] Yeah. So what happened very early on was all this initial excitement kind of faded away because people realized, oh, are the people we’re giving blood to keep dying? You know, there was an early case where a mad man was infused with the blood of a cough, thinking that that would, you know, the cough is so gentle. This will come this sort of, you know, this madman down. And he died. So it was it. It was a huge issue. Part of it was that no one understood transfusion reactions. That’s when you were having a huge allergic reaction to an incompatible blood or blood type, so humans can’t receive blood from a calf, they will have a transfusion reaction. They also can’t necessarily receive blood from another person unless that person has a compatible blood type. And blood types weren’t discovered until 1900 or and not really tested for until the 1920s. So that was a huge kind of lottery element of early blood transfusions was just like luck of the draw. Did you get blood that was compatible or not? You had no way of knowing until you died. Yeah.
Krys Boyd [00:22:05] And then there was the problem of clotting. Right? What did it take to keep donor blood from coagulating before it could be given to a patient who needed it?
Nicola Twilley [00:22:14] Yeah, I had never even thought about this. But, of course, you know, it’s one of blood’s very effective qualities is that it clots up when it is coming out of a hole in us. We need that. Otherwise we bleed to death. But that means if you’re trying to transfuse someone and blood is going outside of the body while it tries to clot up. So in early transfusions, they were done from a living person to a living person, because there was no way to keep the blood of from clotting. Otherwise you just kind of joined people up, you know, hooked them up with a pipe between them. It took until again the early 1900s for a researcher in New York, actually, to discover that you could add a little bit of a chemical called sodium citrate to blood. And it did not damage it in any way, and it stopped it from clotting. And that was pretty exciting, because suddenly you didn’t have to have live person to person transfusions.
Krys Boyd [00:23:14] So now we can store blood, at least for a little while. Talk about how donor blood is processed and distributed today. It’s really a remarkable infrastructure that handles this stuff.
Nicola Twilley [00:23:25] Yeah. It’s astonishing. I was lucky enough to visit the National Health Service blood and transfusion blood factory. Essentially it’s outside of Bristol in the UK. It’s one of the largest blood processing. Again, factories is the only that’s that’s what they call. It’s one of the largest blood processing factories in the world. They take in all the blood that’s donated around the country and sort of separate it into components. And it is astonishing. You walk into this vast factory floor and there are just bags of blood hanging from the ceiling the way that, you know, I don’t know, parts of machines would be hanging in a normal factory. And so it starts, the blood comes in warm and they start it by hanging it on a rack there so that it’s separate. So what happens is the heavier red blood cells, they’re heavy because they have hemoglobin in them. This iron rich protein makes them heavy. They all fall to the bottom. The plasma is on top. And in between is a very thin layer which contains the white blood cells and the platelets. And then from there it’s a whole process of isolating and centrifuges and spinning and testing and filtering. To separate each thing out into its components, the plasma to be frozen. White blood cells get separated out and can be, you know, made into component therapy for people who are going through chemotherapy. Platelets get separated out and jiggled, and red blood cells gets separated out and types and put in the fridge. And all of it goes through quality control checks and disease checks just to make sure it’s okay. And some of it, I mean, it comes in, you know, people’s blood is different. So some of it will come in and can be used. But yeah, there’s it’s a it’s it is a factory and it’s wild seeing what goes into it.
Krys Boyd [00:25:19] In terms of shortages, you know, that it does not help that the population is generally aging all over the world. Is there an upper age limit to when people can safely donate blood? Or is the problem that older folks are more likely to need transfused blood?
Nicola Twilley [00:25:35] It’s both. So yes, folks who are going through heart surgery, going through chemo, they need blood. You know, those those heart bypass machines go through pints of blood. So they definitely need blood and they are less able to give it. It’s it’s often the case that you know this varies. Individual countries have different parameters for this. But it’s basically based on your iron levels. And older folks are often likely to have lower iron levels in the first place. So then they can’t donate.
Krys Boyd [00:26:10] What do doctors do then, when they have a patient who could benefit from a unit of whole blood from a donor, but that unit is not immediately available?
Nicola Twilley [00:26:19] Well, you can use other things in the in the heat of the moment. So right now, for example, There is no whole blood carried on ambulances in the US, even though that would be the number one thing we could do to save lives. The reason it’s not carried in most jurisdictions in the US is because it’s not reimbursable for insurance reasons, which I found outrageous, given that it is the number one thing we could do to save lives. But leaving that aside, what that means the EMTs have to do right now is use the substitute, and what they do is essentially use something. I mean, one surgeon referred to it to me as pasta water, but it’s saline solution. It’s it’s it’s something that sort of replaces the lost volume in the, in your circulatory system. So what happens is when there’s not enough fluid in your circulatory system, then there’s not enough blood pressure to pump oxygen around the body. And so replacing that lost volume with pasta water is, you know, it’s water with some dissolved salts and sugars That is sort of a stopgap solution, so that at least there is enough volume to create enough pressure so that what little red blood cells you have left are able to do their job of being pumped around the body. So that’s that’s the substitute right now. But yes, whole blood should be on ambulances and is not.
Krys Boyd [00:27:47] So Nicki, scientists have been working to develop some kind of blood substitute product for a very long time now. What makes it so hard? This is a deceptively simple question to just whip up some liquid in a lab that would do all the things that natural blood does.
Nicola Twilley [00:28:03] Yeah. Again, I was like, how could this be so hard? And of course, it really is. Yeah. First of all, blood does a lot of different things. So scientists have tried to crack this problem by just sort of narrowing in on some aspect of it. So you know that pasta water I talked about that an EMT will give you that is just replacing the lost volume for blood pressure. That’s just one of blood’s jobs. But they figure, let’s tackle it one job at a time. The biggest, and I guess arguably most essential job that blood does is carrying oxygen around the body. And that’s something that people have tried to find a substitute for. The earlier ones were these chemicals called her fluoro carbons, which were initially developed as part of the Manhattan Project. It’s part of the separation of uranium, but turned out to be really good at carrying oxygen. The problem was, and they were stable and inert in the body. The problem was they didn’t really release the oxygen. Well, you know, it’s kind of hard to find a molecule that will pick up oxygen in the lungs and then let it go in the muscles. How does it know to pick up in one place and let go in the other? In our actual bodies there is a molecule that regulates that. But in, in, you know, a substitute. That’s it. That doesn’t exist. So then as a as I mentioned, after the or the Aids crisis really kind of motivated scientists to look at this and they figured, you know what? We’ll just take that hemoglobin, which is the protein that carries oxygen around. It’s normally inside a red blood cell. But we’ll just take that and we will purify it. And you know we can get it from from cows if need be. Tweak it in the lab and then inject that into people and it will carry blood around. And that’ll be fine. And actually for a while it looked really good. It got far into clinical trials, phase three clinical trials, which is sort of the step before FDA approval. And 2 or 3 big pharmaceutical companies had this in phase three trials, which means they have spent a lot of money on getting it to that stage, and they really think it’s a good bet. And the trials were a disaster. They people. A lot of people died. And they were they were shut down by the FDA. The the hemoglobin, you know, oxygen carriers were not approved. And the field went dark for a while, but it turned out we just didn’t know enough about blood. I mean, one of the things that happens when you try to make a substitute is you realize, well, I didn’t even realize it was doing this.
Krys Boyd [00:30:50] Alright, Nicki, freezing liquid blood is one thing. There’s also been work done to freeze dry red blood cells. I mean, how do you reconstitute those for use in a patient? You’d you just add water to powdered blood?
Nicola Twilley [00:31:04] Well, this synthetic substitute that I saw being injected into rabbits in Baltimore, that is its kind of USP, its unique selling point. You can freeze dry it and just add water and literally shake it up and it’s ready to go, which is revolutionary. I mean, it’s just astonishing. You can go from a lightweight powder that is totally shelf stable, carry it in your in your backpack, and then just, you know, add some water and you’ve got blood.
Krys Boyd [00:31:36] So there are recent blood substitute formulations that have researchers pretty excited. What is this nanoparticle KC 1003.
Nicola Twilley [00:31:48] Yes it is. What the doctor who co-developed it. Guy called Doctor Allen. Doctor; doctor doctor is his name. He calls it the special sauce. And what it does is actually get around this problem where in our own bodies, hemoglobin picks up oxygen in our lungs and releases it in our muscles. And it knows to do that because of an enzyme reaction that is kind of affected differently in the lungs, which are alkaline, versus the muscles which are more acidic. So that’s. That’s what’s regulating that in our bodies. We don’t have that in a substitute until doctor doctor came up with KC 1003. It performs the same trick. Basically, it allows this substitute to pick up a lot of oxygen in the lungs and let it go in the muscles where it’s needed. And that is sort of a huge breakthrough. What’s amazing is you can sort of super stuff it then. So you can you can load up the red blood, substitute the synthetic red blood cell with a particle that your body makes when you exercise that altitude. And so now it’s stuffed full of this, this molecule that is really good at taking up oxygen and really good at releasing it. And the KC 1003 kind of just switches it on and switches it off as necessary. And your body thinks that if you’re in Denver, you’re in Saint Louis, you’re in Denver, you’re in Saint Louis. Depending on where this particle is in your lungs or in your muscle. So it it’s it’s a really nifty little trick to get around the fact that you have to convince hemoglobin to let go of oxygen, your muscles and pick it up in the lungs. And we have a way to do that with red blood cells naturally in our body that we don’t even think about. But until scientists figured out how to copy that, we had a real problem creating a substitute.
Krys Boyd [00:33:59] Is this nanoparticle what is the sort of killer app in this specific formulation?
Nicola Twilley [00:34:06] Yes it is. It’s the it is the killer app. It’s the special sauce. It really is. There are two things going on that make this different, I think, from previous attempts to create an artificial blood. One is the KC 1003, and the other is the fact that the hemoglobin is safely sheathed in this nanoparticle. Because it turns out that if hemoglobin is just freely floating around, as it was in those pharmaceutical trials in the 90s, these deadly ones, it’s actually a disaster. It goes around scavenging something called nitric oxide, which is the particle that’s telling your capillaries in your your circulatory system to open to stay open. So again, we did not know that until the 90s. But that means you can’t have hemoglobin just floating around the body without a cover basically. And so figuring out a way to make a nanoparticle that acts as a cover was really essential.
Krys Boyd [00:35:10] What about shelf stability? How long does this stuff keep?
Nicola Twilley [00:35:17] I mean, I haven’t aged it for a decade or so yet because it hasn’t existed that long, but it’s theoretically shelf stable for years. Wow. Because what you can, you can freeze dry it and just keep it totally inert until you add water. So, I mean, I don’t imagine it would last for eternity, but it’s certainly going to last months and years, which is a lot better. That means you can build up a stockpile, for example, which is incredible. I mean, this is being developed for military purposes. And so it’s relevant to point out here that NATO did a study looking at how long blood would last in Europe, blood supplies, if a NATO country like Estonia went to war with Russia. The answer was one day. One day. So there and there is no way to stockpile because it it it goes bad. We can’t store it for long enough. So something like this would allow you to build up a stockpile.
Krys Boyd [00:36:22] What sort of testing has DARPA conducted on this stuff?
Nicola Twilley [00:36:26] Yeah, DARPA is very excited about this research, for obvious reasons. And they invested $46 million in early 2023. And their goal is to combine arrhythmia, which is the synthetic red blood cell that is developed by doctor doctor in Baltimore to combine it with synthetic platelets, which are the clotting element of blood and freeze dried plasma just from regular donations into a whole blood substitute that can be freeze dried and just reconstituted in the field by, you know, a field medic and just given to soldiers right out there in the, you know, in the dark, in the middle of a live fight, wherever it’s needed. And so DARPA has invested heavily in this whole blood substitute, which is currently being tested in rapids and appears to be working well. I mean, I saw it being injected into rabbits and it it did work in 50% of the cases to rabbits. So there’s good data. It’s definitely not ready for prime time yet. But that’s, that’s the investment right now.
Krys Boyd [00:37:39] And again, as with ambulances, the idea is that people with traumatic injuries who receive donor blood as soon as possible, or a substitute for it, are more likely to survive long enough, at least to get to a hospital.
Nicola Twilley [00:37:53] It’s the single most change making thing we can do. It’s this has the single biggest impact is how quickly we can give blood to folks. Not, you know, how well trained or the EMTs. Or are there more EMTs or any of those things? It’s how soon can you get blood? I mean, the way doctor doctor put it to me made perfect sense. You wouldn’t wait ten minutes, 15 minutes, half an hour to start CPR. Everyone knows you have to start it right away. Well, it’s the same with blood. If you don’t have blood bringing oxygen to your organs. That’s bad. You’re going to die. So it is a matter of urgency. And the idea is that having this available. So you reconstituted in demand in what the Army calls austere situations, which basically means you don’t have a fridge, you don’t have a hospital, you know, you can’t tap into the resources of a normal trauma center, then this will this will save lives in those in those circumstances.
Krys Boyd [00:38:57] Is the hope, Nicki, that medics could give as much of this substance as someone has lost in real blood. Like is there a like a limit to the ratio of artificial blood to real blood?
Nicola Twilley [00:39:10] Yeah. They’re actually designing it so that you don’t need as much of it so it carries more oxygen than regular blood. It can pick up more and it can release more. That’s the way they’ve designed it, so that you don’t need to replace it one for one, so that you can have a smaller dose and still be functional. And that’s because it’s not designed to be something that you, you, you just walk around filled with synthetic blood. No, it’s a bridge. It’s designed to get you to the hospital where you can be patched up and have have you have your own regular blood, get you sort of fill you up again, as it were. So it is a bridge therapy. It’s designed to to bridge the gap between wherever you get injured, where you really need that blood, and the hospital where you can get treatment.
Krys Boyd [00:40:07] So on the other side of this research, we have efforts to cultivate actual blood cells from stem cells. We talked about this a little bit at the top of the interview. This is the lab grown meat version of blood substitutes. What sort of progress have scientists made?
Nicola Twilley [00:40:23] So to you or me this might sound slow, but we actually only discovered stem cells, human stem cells isolated in the late 90s. So the fact that we can even isolate them and grow blood here in 2025, I think is super impressive. And this is already in human trials, which is great progress. That is in human trials in healthy humans. So that’s typically you go from lab work to animal trials to trying your product in healthy humans to then trying it in the target audience, the people who need it. And so right now, this lab grown blood is being injected into healthy humans in the UK. Again, this is a step to make sure of safety, and also a step to make sure that the body doesn’t just reject it automatically and kind of throw it out in the trash that it carries on circulating, acting like a blood cell.
Krys Boyd [00:41:24] Are they trying to make formulas that are closest to a universal donor quality of blood?
Nicola Twilley [00:41:32] Yeah. So the idea with this is that you would be able to make a universal version right now. This for this test, they’re matching donors with recipients and growing it. So it’s it’s it’s tailored as it were, for the recipients. And that’s because it’s going in to healthy humans. And these people need to not be put at risk. I mean, do no harm is sort of the the first the first goal there. So they’re already taking a risk having this lab grown blood injection then. So the idea is to match their own blood as closely as possible. Ultimately, you should be able to tailor it. You should be able to make it universal. You should also be able to tailor it for extremely rare blood types. You should even be able to tweak it to have more of certain things and less of others. So, for example, one of the doctors I spoke to, Cedric Ghevaert, he’s working on people who’ve observed that there are if there’s a particular protein content in your platelets that can help with recovery after a heart attack. So it’s possible we could grow platelets that have more of that protein content in them. And then that would be the the the flavor of blood you get after a heart attack. So once we figure out how to grow it, which we have, you can theoretically do all sorts of things. The issues are that we can only grow to to taste at two tablespoons full at a time right now. Though, it’s not a lot.
Krys Boyd [00:43:09] Yeah. Is the problem of scalability about money, or is it about just how long it takes to make this stuff?
Nicola Twilley [00:43:16] Well, it does take 21 days to grow blood. That’s just sort of a non-negotiable right now. And the scale issue is definitely it’s partly money. I mean, the one of the issues is, you know, that tiny syringe full of lab grown blood that cost $75,000, just not even counting the research that went into it or the, you know, blood, sweat and tears of the the researchers who figured out how to grow it, just the the materials, as it were, in the time. So that’s, you know, in contrast to that 200, 250 bucks pint for donated red blood cells, it’s difficult economics. And so, yes, there needs to be a huge investment to be able to grow red blood at scale. That’s something that you need, you know, millions of dollars to figure out.
Krys Boyd [00:44:11] So are scientists willing to talk about a timetable when they think it might be that this technology could be perfected to the extent that it’s widely available?
Nicola Twilley [00:44:21] Well, so the plan and I think this is smart with lab grown blood, is to tap the pharmaceutical industry funding to get it to scale. So they won’t be growing blood for you and me anytime soon. What they’ll be doing is growing special red blood cells that have been engineered to, say, release a particular enzyme in the body. So they’ll be like therapeutics rather than than just plain blood, as it were. And with that, if Big Pharma, which it it is interested, can invest in those kinds of red blood cells, sort of these drug versions of red blood cells, then we might get the progress to get to the growing red blood cells at scale for you and me. All of that, I mean, gosh, like in the lab right now, they’re showing they can grow these red blood cells that that, you know, can hide novel enzymes and deliver therapeutics. Those have to go through animal trials. Those have to go through trials in humans. Those have to get FDA approval. There’s no way to do that in under a decade. So, you know, basically, if you need blood right now, you are going to be getting donor derived blood. You hope if there’s any around through for at least the next ten years.
Krys Boyd [00:45:42] Nicola Twilley is co-host of the podcast Gastropod and a contributor at The New Yorker, which published her article “The Long Quest for Artificial Blood.” Nicki, it’s always nice to speak with you. Thanks for making time.
Nicola Twilley [00:45:54] Thank you so much. It’s always a pleasure to be on the show.
Krys Boyd [00:45:56] Think is distributed by PRX, the Public Radio Exchange. Again I’m Krys Boyd. Thanks for listening. Have a great day.
