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0:01:06 Every year, 60,000 people in the United States and 2 million people around the world
0:01:09 die because of blood loss.
0:01:14 They get in a car accident or they get shot and they bleed to death.
0:01:18 These people tend to be relatively young and healthy,
0:01:21 and a lot of them could be saved if they were quickly given blood.
0:01:25 But outside the body, blood doesn’t travel well.
0:01:26 It’s bulky.
0:01:27 You have to keep it cold.
0:01:33 And as a result, it’s hard to get blood to patients when they urgently need it.
0:01:36 Ambulances don’t tend to carry it.
0:01:38 Field medics don’t typically have it in combat.
0:01:41 And so there’s long been this dream.
0:01:47 What if we could come up with a way to make blood easier to store and transport?
0:01:54 What if we could have blood ready to go every time an ambulance gets to a car accident and a medic gets to a wounded soldier?
0:02:11 I’m Jacob Goldstein, and this is What’s Your Problem, the show where I talk to people who are trying to make technological progress.
0:02:13 My guest today is Alan Docterr.
0:02:17 He’s the co-founder and chief scientific officer at CaliSite.
0:02:19 Alan’s problem is this.
0:02:27 Can you make something like freeze-dried blood that can be rehydrated and given to patients when and where they need it?
0:02:30 Alan didn’t start out wanting to found a company.
0:02:33 He was a doctor taking care of kids in the hospital.
0:02:47 So the type of medicine I do is intensive care medicine, and for children, looking after children in the hospital who have severe infections or major injuries, and they’re critically ill.
0:02:51 And most of them are in a condition we call shock.
0:02:59 And the problem with shock is that you’re not effectively getting blood and oxygen where it’s needed.
0:03:00 Okay.
0:03:05 So people get sick and die, even though we fix the underlying problem.
0:03:16 So we can cure the infection, we repair the hole in the blood vessel, and people still, we lose them because, you know, their circulatory system is failing.
0:03:21 You know, that was frustrating, and I was interested in that problem, and I was trying to understand why that happened.
0:03:32 And what we were able to learn is there’s a traffic control system in our circulatory system that routes blood where it needs to go.
0:03:36 And red blood cells are the traffic lights.
0:03:42 So they turn green and they open up the blood vessels, or they turn red and close them.
0:03:44 And it’s very coordinated.
0:03:47 It’s a very exquisitely tuned system.
0:03:50 And I was studying that system.
0:03:50 Huh.
0:03:56 That’s governed by the way hemoglobin interacts with other chemicals in our bloodstream.
0:04:05 And it turns out it’s highly relevant for shock and fixing shock, but it turns out it’s also relevant for transfusion.
0:04:08 And that’s when this story started.
0:04:18 So you’re studying red blood cells and hemoglobin, which are obviously hemoglobin are the molecules that transport oxygen, right, that do that key function of blood.
0:04:26 That is the thing in particular that you want to replace when somebody gets shot or gets in a car accident, right, of all the things in your blood.
0:04:31 The thing you need urgently that minute is hemoglobin to deliver the oxygen, right?
0:04:41 People had known that part for a long time and had tried to develop blood substitutes in particular to solve this acute kind of trauma-setting problem.
0:04:43 But it had gone badly, right?
0:04:55 So tell me about the history up until that point of people trying to come up with ways to, you know, get hemoglobin to people in emergencies, do sort of hemoglobin replacements.
0:04:58 Well, they did the first obvious thing.
0:05:05 So the problem is you have to make the blood shelf stable in order to use it outside of hospitals.
0:05:07 So you have to get rid of the cold chain.
0:05:13 The reason we need the cold chain is the hemoglobin is inside a red blood cell.
0:05:17 The red blood cell is alive and it needs glucose.
0:05:19 It needs all kinds of things.
0:05:26 And it has to be kept cold or it goes bad, sort of like the way milk has to be kept cold or it goes bad.
0:05:31 And you can’t leave it outside the fridge too long or you can’t drink it.
0:05:32 Same thing with blood.
0:05:39 So they say, okay, if we just take the hemoglobin out of the red cell, will it still capture and release oxygen?
0:05:41 Yes, it will.
0:05:42 So far, so good.
0:05:43 So far, so good.
0:05:47 Does it need to be kept cold in order to work?
0:05:49 No, it doesn’t.
0:05:51 So it’s shelf stable.
0:05:55 Does it work if we put it inside animals?
0:05:57 Pretty much it does.
0:06:01 And so everybody’s like, okay, let’s try this.
0:06:03 And it was a catastrophe.
0:06:05 So it wasn’t just ineffective.
0:06:07 It was harmful.
0:06:09 So it was more harmful than the controls.
0:06:15 So it caused heart attacks and strokes and death in the people that got the blood.
0:06:17 Why is it bad to give people hemoglobin?
0:06:20 That is a surprising outcome, right?
0:06:22 It’s not like it’s some novel molecule.
0:06:24 It’s our bodies are full of hemoglobin.
0:06:25 All right.
0:06:28 So what it meant was we didn’t understand something.
0:06:33 It turns out hemoglobin does more than just interact with oxygen.
0:06:36 It interacts with other chemicals in the bloodstream.
0:06:44 So the hemoglobin has to be sheathed inside a membrane, and it sequesters the hemoglobin from
0:06:49 everything else in the bloodstream, from the blood vessels, the cells that line the blood
0:06:55 vessel, from the chemicals in the bloodstream, where it won’t do things it’s not supposed
0:06:55 to do.
0:07:01 And it turns out that when hemoglobin is free in the bloodstream, the blood vessels don’t
0:07:06 know whether to open or close, and what they end up doing is mostly closing.
0:07:06 Uh-huh.
0:07:11 So that’s why people who got just naked hemoglobin had heart attacks, basically.
0:07:12 Exactly.
0:07:12 Yeah.
0:07:13 Yeah.
0:07:13 Exactly.
0:07:14 Got it.
0:07:14 So, okay.
0:07:16 So this is the context, right?
0:07:22 So it’s clear, bad idea to just give people hemoglobin, alas.
0:07:23 Well, it was a good idea at the time.
0:07:26 It seemed like a good idea, but it became clear that it had been a bad idea.
0:07:28 It’s scary, in fact, right?
0:07:28 It’s scary.
0:07:30 Like so many things we’ve all done.
0:07:33 Yeah, yeah, no, no shade on the people who tried it.
0:07:37 It’s just, it’s a terrible outcome that nobody would have wanted.
0:07:45 So you, meanwhile, are studying hemoglobin, and then a chemical engineer comes to you with
0:07:45 an idea, right?
0:07:46 Tell me about that.
0:07:48 2010, what happened?
0:07:54 Yeah, I’m just studying regular red blood cells and this routing problem, right?
0:07:54 Which I understood.
0:08:01 That’s why, you know, a lot of these blood substitutes, what we call the unencapsulated
0:08:02 hemoglobins, failed.
0:08:06 People started to understand that, but I wasn’t thinking like, oh, I know how to solve that
0:08:07 problem.
0:08:11 I was minding my own business doing something completely different.
0:08:18 The chemical engineer, the bioengineer, was making special particles, nanoparticles for
0:08:18 imaging.
0:08:27 So there’s a new form of medicines and therapies where you make little fat droplets, and you
0:08:33 can decorate them with all kinds of molecules that either home to different parts of your
0:08:35 body, and you can see them on x-ray.
0:08:37 You can put drugs inside.
0:08:39 You can do all kinds of things with them.
0:08:44 Well, just to be clear, these fat droplets, as you’re describing them, like, they were the
0:08:48 technology used to encapsulate the COVID vaccines, right?
0:08:48 That’s right.
0:08:53 The RNA COVID vaccines were in, well, lipid nanoparticle is the jargon, right?
0:08:54 Although I like fat droplets.
0:08:54 Exactly.
0:08:55 I appreciate fat droplets.
0:09:02 So yeah, liposome was used for, or a fat droplet was used for the COVID vaccine, and it’s
0:09:03 used for other things, too.
0:09:14 So what Dr. Pan, Depanjan Pan, brilliant chemical engineer, so he was making particles so that you
0:09:15 could see specific things.
0:09:18 So you want to be able to see breast cancer.
0:09:20 You want to be able to see a blood clot.
0:09:23 You want to see, you know, a particular type of cell.
0:09:30 Then you put something on a fat droplet that finds that cell, and you put a little metal in
0:09:34 the droplet that you can see with a special CT scan.
0:09:41 And then say, suddenly, I see very small and tiny, hard-to-detect cancers, and so on.
0:09:47 And so he was making these particles, and he was doing them in a way he wanted to make a lot of
0:09:52 surface area, and he ended up making particles that looked like red blood cells.
0:09:52 Huh.
0:09:54 Just by happenstance.
0:09:58 He just looked at one and said, hey, I know what that looks like, a red blood cell.
0:10:04 So red blood cells are also trying to have a lot of surface area because they exchange gas.
0:10:10 And he was trying to create a lot of surface area for a different reason, so he could decorate the
0:10:11 particles with these proteins.
0:10:16 I was looking at red blood cells today, trying to think of what they look like, and I thought of
0:10:24 biali, which is kind of a niche analogy, like a bagel, but with a thin, doughy part in where the hole would be.
0:10:27 Do you have a go-to description of a red blood cell?
0:10:28 That’s what we use.
0:10:30 They’re called nano-bialis.
0:10:31 Oh, no kidding.
0:10:31 Yes.
0:10:32 Okay.
0:10:35 Or the other word, people say, a biconcave disc.
0:10:38 Yeah, that’s less salient.
0:10:38 Less cool.
0:10:39 That’s right.
0:10:39 Okay.
0:10:42 So does he come to you with this idea?
0:10:43 Right.
0:10:44 So what happens?
0:10:46 He’s like, oh, that looks like a red blood cell.
0:10:46 What does he do?
0:10:51 So he thought, hey, I wonder if I could put hemoglobin inside.
0:10:52 Uh-huh.
0:10:59 And he was loosely familiar with the problems with auction carriers, and he says, I wonder
0:11:01 if I could just put hemoglobin inside.
0:11:04 And he figured out how to do that.
0:11:08 And then he’s like, oh, I don’t know how to tell if this works or not.
0:11:15 So we’re both at WashU, and WashU has this collaboration website where you can Google, or it’s like Googling,
0:11:18 that it’s just at WashU, the university.
0:11:18 Oh, interesting.
0:11:21 Like an internal search engine.
0:11:21 Uh-huh.
0:11:21 Yeah.
0:11:27 So he searched red blood cell physiology, and I popped up.
0:11:33 And so he called me and told me the story and said, you know, why don’t you come over to
0:11:39 my lab, and I’d like to show you what we’re doing and see if this works, and maybe we could
0:11:41 figure out how to collaborate.
0:11:43 Well, it didn’t work.
0:11:44 Huh.
0:11:44 But-
0:11:46 Wait, what do you mean it didn’t work?
0:11:46 It didn’t work.
0:11:47 I was all ready for it to work.
0:11:48 What happened?
0:11:48 Yeah.
0:11:55 Well, there’s a little more to it than just putting hemoglobin inside a fat droplet.
0:11:55 Yeah.
0:12:02 So what I realized is, conceptually, this would solve the problem that the unencapsulated
0:12:07 hemoglobins were plagued by, that this were like little red blood cells.
0:12:14 And if we could figure out the chemistry to make this capture and release oxygen, that maybe
0:12:16 this would, you know, make things safe.
0:12:18 And you can freeze dry these things.
0:12:23 So they could be, you know, shelf stable and very lightweight.
0:12:26 So it’s like instant coffee, but for red blood cells.
0:12:27 That’s the dream.
0:12:28 Yeah.
0:12:29 Yeah, exactly.
0:12:36 So initially it doesn’t work, but you realize that the idea is fundamentally plausible.
0:12:43 So like, what are the things you have to sort of figure out, make work for this to work?
0:12:48 A number of things from the inside out.
0:12:48 Okay.
0:12:53 So first of all, you’ve got a droplet that has hemoglobin inside it.
0:13:00 Hemoglobin, the reason red blood cells work, they’re a lot more than just bags of hemoglobin.
0:13:03 They have lots of other functions.
0:13:08 And so we had to decide, what are we going to keep and what do we get rid of?
0:13:11 Because you can’t build the whole red blood cell.
0:13:12 We don’t know how to do that.
0:13:13 It’s crazy.
0:13:16 You want to do as little as you can get away with, right?
0:13:17 Right.
0:13:21 You want the stripped down basic thing.
0:13:23 And so it just has to transport oxygen.
0:13:27 And then it has to not do a bunch of other things.
0:13:29 We don’t want it to cause trouble either.
0:13:34 Well, and subtly, subtly, when you say transport oxygen, it has to know when to pick up oxygen
0:13:39 from the lungs and has to know when to release oxygen to whatever tissue needs it, right?
0:13:43 Like, that part seems hard from the outside.
0:13:44 Right.
0:13:45 Well, they’re opposites.
0:13:46 Yeah.
0:13:47 Yeah.
0:13:49 And it has to do it at the right time, right?
0:13:50 It has to do it in the right setting.
0:13:51 Yeah.
0:13:53 At the right speed.
0:13:53 Yeah.
0:13:56 So, yeah, it’s all very finely tuned inside our body.
0:14:00 So we had to try to imitate the behavior of a real red cell.
0:14:01 Yeah.
0:14:08 So, and the real red cell has, people understand like, okay, there are these other molecules
0:14:15 inside red cells that modify the way the hemoglobin interacts with oxygen that causes it to capture
0:14:21 oxygen effectively in the lung and then let go when it gets out in tissue.
0:14:21 Okay.
0:14:25 And the red cells responding, the red cell doesn’t know, oh, I’m in the lung.
0:14:27 Oh, I’m in the lip.
0:14:29 I’m in the muscle.
0:14:29 Right.
0:14:34 So it’s looking for cues.
0:14:34 Yeah.
0:14:41 So it doesn’t have a map, but it can almost smell where it is because of the chemicals that are
0:14:44 different in the lung than in exercising muscle.
0:14:51 So, and it’s primarily responding to the amount of acid and the amount of carbon dioxide that’s
0:14:52 in the blood.
0:15:02 And so what we did is we created responsive elements that would work like red cells, but in a different
0:15:09 way so that they would change their shape or change their ability to interact with other
0:15:15 molecules in response to those two signals, carbon dioxide and acid.
0:15:22 So then the artificial red cell, quote, knows it’s in the lung or knows it’s in the muscle.
0:15:24 So we call that wet wear.
0:15:31 So it’s like a thousand little thermostats inside each little particle.
0:15:34 And it’s telling the hemoglobin what to do.
0:15:37 I’m sure there are a lot of hard parts, but that sounds like the hard part.
0:15:40 Well, that was, yeah, that was one of the hard parts, right?
0:15:44 Then we have to make it silent to the immune system.
0:15:48 So our body doesn’t recognize it.
0:15:52 We have to make sure that it doesn’t alter the viscosity of blood.
0:15:55 So it doesn’t get too thick or too thin.
0:16:00 And then we have to make sure it doesn’t interact with the blood clotting system.
0:16:03 It doesn’t cause blood clots or interfere with blood clots.
0:16:06 And then we have to make it freeze dry.
0:16:13 And then, you know, we have to make it circulate for a long time.
0:16:19 We have to evade the body system for clearing things that shouldn’t be in our blood out of our blood.
0:16:25 And so once we solve all those things, you know, then, you know, now it’s working in an animal model.
0:16:35 And that’s why the very first one didn’t work, because while Dr. Pan had already figured out how to get hemoglobin inside the fat droplet, it didn’t do any of these other things yet.
0:16:39 So is there a moment when you decide, oh, we should start a company?
0:16:40 Yes.
0:16:50 And so we started the company when we had first demonstrated proof of concept that we could create an artificial red cell.
0:16:53 At that point, we have a different task.
0:17:00 So the original academic task was, can we design an artificial cell?
0:17:02 Can we prove that it works?
0:17:10 Once we’d done that, we now have a development, commercial development task, which is, can we make it reliably?
0:17:12 Can we make it over and over again?
0:17:13 Can we make a lot of it?
0:17:20 Can we make sure that it passes all the safety and efficacy criteria at FDA?
0:17:23 So that task, we need a company for.
0:17:25 It’s very different than a university task.
0:17:28 And that’s when we formed Kalosite in order to do those things.
0:17:34 We’ll be back in just a minute.
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0:18:18 Imagine that you’re on an airplane and all of a sudden you hear this.
0:18:26 Attention passengers, the pilot is having an emergency and we need someone, anyone, to land this plane.
0:18:27 Think you could do it?
0:18:35 It turns out that nearly 50% of men think that they could land the plane with the help of air traffic control.
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0:18:39 It’s just…
0:18:39 I can do it in my eyes closed.
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0:19:21 Write that in 2023, you got a $46 million DARPA grant, or were part of that.
0:19:21 Tell me about that.
0:19:24 That seems like a big moment in the history of this project.
0:19:25 That was the moment, yeah.
0:19:27 I have to say.
0:19:34 So, we had been working on, in a reasonably successful way, developing the red blood cells, artificial red cells.
0:19:38 But what DARPA wanted, DARPA wanted everything.
0:19:41 They wanted all the function of blood.
0:19:44 So, the ability to clot.
0:19:51 So, for a soldier, basically, if you need artificial red cells, it’s because you’re bleeding.
0:19:52 By definition.
0:20:03 If you just replace the red cells, and you don’t replace the clotting factor, then it’s like pouring blood into a sieve.
0:20:05 It just falls back out again.
0:20:07 It’s ineffective.
0:20:11 So, they realize that we need to be able to replace everything.
0:20:15 And to do that, at the point of injury, you need freeze-dried plasma.
0:20:17 You need freeze-dried platelets.
0:20:19 You need freeze-dried red cells.
0:20:21 And it has to be scalable.
0:20:24 And, you know, there are a lot of logistic concerns.
0:20:33 So, if they put out a call for applications for teams to form from the people who are working on each of those components,
0:20:47 And everybody had just been working on them separately, to come together and form a consortium that would figure out how to make all these different components compatible and equivalent to stored blood.
0:20:53 So, we built a consortium to do that, and we competed effectively to win that award.
0:20:58 What is the status of the, what do you call it, artificial whole blood?
0:20:59 What do you call the whole package?
0:21:02 Unfortunately, we don’t have a very sexy name for it yet.
0:21:04 We call it the whole blood analog.
0:21:10 So, you know, it’s not completely artificial because it’s a biologically derived plasma.
0:21:13 It’s just regular plasma that’s been freeze-dried.
0:21:13 Okay.
0:21:15 The platelets are fully synthetic.
0:21:19 So, they help, you know, form blood clots.
0:21:20 To stop the bleeding.
0:21:24 To stop the bleeding, which is, you know, that’s why they’re getting this material.
0:21:24 Yeah.
0:21:28 And so, we sort of have two threads going now, right?
0:21:34 There’s how is it going on your artificial red blood cells, and then how is the whole blood analog project going?
0:21:35 So, let’s just take those in order.
0:21:43 Like, what is the status of the, like, are you testing the artificial red blood cell on its own in clinical trials?
0:21:45 Is that part of the plan, to do that by itself?
0:21:47 Or do you, does it need to be the whole package?
0:21:50 Well, it has to be tested by itself first.
0:21:51 Yeah.
0:21:55 And so, it’s a standalone element.
0:21:59 And so, we are still in what’s called preclinical testing.
0:22:02 So, we’re testing in animal models.
0:22:14 And in parallel, we’re developing the combined product, which will be sequentially administered plasma, O2 carrier, and platelet.
0:22:17 And that’s also in preclinical testing.
0:22:19 The O2 carrier is the red blood cell, is what you’re making.
0:22:20 Is the red blood cell.
0:22:21 That’s right.
0:22:23 And plasma and platelet.
0:22:26 And that is expected that will follow.
0:22:32 So, we have to first test each element by itself before we start mixing cocktails.
0:22:34 That’s so hard.
0:22:43 Like, I feel like the way fractional probabilities work, if a bunch of things have to work separately, and there’s some, you know, the fractions multiply, right?
0:22:47 So, it gets less and less likely that it will work, just probabilistically.
0:22:47 Right.
0:22:52 But what we have the ability to do is adapt to what we find.
0:22:52 Yeah.
0:22:54 And that’s what we’ve had to do.
0:22:58 So, we took these components and, of course, they didn’t automatically work all together.
0:23:05 So, we weren’t able to just take the red blood cells and the plasma and the platelets and just put them in a blender and get blood.
0:23:07 So, we’ve had to tune.
0:23:17 We’re actually now on version 4.12 of the, starting with version 0 of the system.
0:23:19 Of the whole blood, of the whole blood analog.
0:23:20 Yes.
0:23:20 Yeah.
0:23:20 Okay.
0:23:23 And is it right that there are other groups?
0:23:26 Is there a group in Japan working on something similar?
0:23:30 Tell me about that and tell me about the field more broadly, other similar projects.
0:23:30 Sure.
0:23:43 The other main encapsulated program is in Japan, led by a really successful scientist named Hiromi Sakai.
0:23:52 He’s been working on this for over a decade, developing another, it’s very, it’s essentially the same concept.
0:23:55 It’s a liposome with hemoglobin on the inside.
0:23:56 A fat droplet.
0:23:57 A fat droplet.
0:23:58 Yeah.
0:23:58 Right.
0:23:59 It’s a fat droplet.
0:23:59 Yeah.
0:24:01 And it’s a little different.
0:24:04 It doesn’t have that wet wear system that we talked about.
0:24:05 Okay.
0:24:10 He has adjusted the oxygen affinity to be sort of in the middle.
0:24:15 So, it’s pretty good at capturing oxygen in the lung and pretty good at letting it go.
0:24:19 And tissue, it doesn’t shift up and down depending on where it is.
0:24:21 So, it’s good enough.
0:24:22 It works.
0:24:25 And he’s already begun to test its safety in humans.
0:24:27 Now, it’s not freeze-dried.
0:24:29 It’s still in water.
0:24:29 Okay.
0:24:34 And they are not working on combining it with plasma and platelets.
0:24:35 It’s just the O2 carrier.
0:24:39 How do you think it’s going, the Japanese version?
0:24:40 Great.
0:24:41 They’re out in front.
0:24:42 Yeah.
0:24:48 So, they’ve tested in humans and they had some minor issues that I think have been probably
0:24:49 been addressed.
0:24:51 And it’s incredibly exciting.
0:24:54 We’re all benefiting from Dr. Sakai’s leadership.
0:24:59 So, to return to your own work and the work of the consortium that you’re part of, what’s
0:25:00 the happy story?
0:25:05 Like, how long in the future do you think about and what do you think about when you think about
0:25:05 it going well?
0:25:13 So, if you think about it going well, I guess there’s a presumption baked into that question.
0:25:17 Mostly, I think about, you know, how it’s not going to go well.
0:25:18 Okay.
0:25:19 Well, how might it not go well?
0:25:23 I mean, I guess that one’s easier to imagine in some ways, but how might it not go well?
0:25:27 I mean, what I’m really worried about is the things I can’t imagine.
0:25:31 So, the things we imagine, we’re constantly trying to think of how it won’t go well and
0:25:34 we try to anticipate a solution to the problem.
0:25:36 And fix it.
0:25:40 The things that we can’t plan for, of course, are the things that we don’t yet understand.
0:25:42 The Rumsfeldian unknown unknowns.
0:25:43 Yeah.
0:25:44 You beat me to it.
0:25:44 Yeah.
0:25:45 Yeah.
0:25:51 So, and that happens monthly, where it’s like, oh, we didn’t think of that.
0:25:53 Now we have to solve a new problem.
0:25:53 Yeah.
0:25:55 Because we’re off the map.
0:25:58 You know, we don’t really, nobody’s been here before.
0:26:01 So, we have to figure those things out.
0:26:03 Does it seem impossibly hard?
0:26:08 Like, frankly, this one, this project just seems so hard.
0:26:09 Right.
0:26:09 It is hard.
0:26:12 If it were easy, it’d be done already.
0:26:17 But the wonderful thing is that I think that we have all the tools that we need to solve
0:26:18 the problem now.
0:26:24 The advances in synthetic chemistry are impossible to overstate.
0:26:32 The advances in nanomedicine and nanofabrication are, you know, allowing us to respond in very
0:26:33 quick ways.
0:26:39 The ability to use machine learning and artificial intelligence to improve our design is reducing
0:26:42 the need to do thousands and thousands of experiments.
0:26:48 So, we can use the computers to tell us the likely things to work.
0:26:51 And it reduces the empiric burden.
0:27:01 And we’ve got great resources because the NIH and Department of Defense, DARPA, have put a lot
0:27:02 of resources in our hands.
0:27:11 So, we’re very fortunate in that we can very quickly respond to the problems that we encounter.
0:27:15 So, it works very effectively in the models that we have.
0:27:18 But now, we also have to make this scalable.
0:27:21 So, that’s another huge challenge.
0:27:27 So, we have to go from making what you might call craft beer to Budweiser.
0:27:31 And just to be clear, it’s made from real blood, right?
0:27:36 Like, the hemoglobin in your lipid nanoparticles is hemoglobin from people, right?
0:27:38 It’s not synthesized.
0:27:40 So, that is a scale challenge right there, right?
0:27:42 That’s impossible, right?
0:27:46 So, we can’t synthesize hemoglobin from amino acids.
0:27:49 That is beyond our current capability.
0:27:54 But we can program other organisms to make it for us.
0:27:55 Like yeast?
0:27:56 Ideally yeast, right?
0:27:57 Put it in a vat?
0:27:57 That’s right.
0:27:58 Is that the…
0:27:58 Yeah.
0:28:00 Yeah, we’re going to brew it.
0:28:07 So, we have a yeast project where we are training yeast to make human hemoglobin and to secrete it.
0:28:07 Yeah.
0:28:10 And that will eventually be our source.
0:28:11 So, okay.
0:28:16 So, take 30 seconds off of thinking about all the things that can go wrong and that you have to figure out.
0:28:24 And just tell me if someday you or the people who come after you, even, respectfully, figure out how to do all the things you’re trying to do.
0:28:25 What will it look like?
0:28:30 Well, we actually, believe it or not, have done that.
0:28:34 We have a prototype of the delivery system.
0:28:41 We’ve been simultaneously trying to work with the people who would be using it so that we don’t end up with an end product.
0:28:44 And they say, but did you think about yeast?
0:28:44 Yeah, yeah, yeah.
0:28:46 And we’re just like, uh-oh, no.
0:28:50 So, a person gets in a car accident or a soldier gets shot on the battlefield.
0:28:54 What happens in this future where the thing you’re working on works?
0:28:57 So, what they’ll have is a kit.
0:29:00 And in the kit will be three components.
0:29:03 The O2 carrier, the plasma, and the platelet.
0:29:05 All of them will be dry powders.
0:29:06 Okay.
0:29:13 So, the instructions that we got from the Department of Defense were, it has to work in the dark, in a ditch, under fire.
0:29:14 Ah, okay.
0:29:19 And it has to be usable by somebody who has basically no medical training.
0:29:19 Yeah.
0:29:25 So, that’s basically, you know, not a sophisticated nurse or a scientist.
0:29:27 Basically, they want you to make instant coffee, but for blood.
0:29:32 But for blood, but also, it’s instant coffee is too complicated.
0:29:39 You’ve got to heat the water, you’ve got to dispense it from a jar into a cup and pour the water.
0:29:41 You can’t do any of that.
0:29:51 So, what we have is a system that has a split bag with a dry side and a wet side, and something called a weak weld.
0:29:55 So, when it’s folded over, you can stand on it, and it won’t open.
0:30:07 But when you unfold it, you squeeze it, and it pops, and the water migrates from one side to the other and hydrates the dry material.
0:30:08 Okay.
0:30:16 And then it sloshes around in there for about a minute, and then you hang it, and you can use it just like a unit of blood.
0:30:17 Right.
0:30:21 You hang it like a bag that goes into your arm on an IV when you’re at the hospital.
0:30:26 And there’s one like that for the plasma, and the platelet’s a little different because it’s a much smaller volume.
0:30:29 That eventually will be what’s called an auto-injector.
0:30:31 Everybody’s seen EpiPens.
0:30:31 Yeah.
0:30:33 So, it’ll be like an EpiPen.
0:30:35 Now, there’s an additional problem.
0:30:36 Damn.
0:30:37 Yes.
0:30:40 There’s two other problems, really.
0:30:47 So, one is, for it to be shelf-stable, it can’t interact with oxygen in the air.
0:30:48 Uh-huh, uh-huh.
0:30:53 So, water and iron and oxygen equals rust.
0:30:57 Yeah, when you think about hemoglobin, it seems like rust, right?
0:31:00 Hemoglobin, it’s iron in the hemoglobin that is binding to the oxygen, right?
0:31:04 And I’m like, wait, is hemoglobin just rusting all the time in my blood?
0:31:04 It is.
0:31:07 In fact, right now, your hemoglobin is rusting.
0:31:11 About 10% of it is rusting constantly.
0:31:15 But you have a rust remover inside your red blood cells.
0:31:24 That is, every time it goes around, there’s a little molecule in there that’s scrubbing the rust and polishing the iron.
0:31:28 So, we have to prevent that from happening during storage.
0:31:35 And to do that, we have to have a plastic, soft plastic, but that has glass-like properties.
0:31:38 So, it doesn’t allow water or oxygen through it.
0:31:45 And so, that’s a very novel film that we are applying for the first time to blood storage.
0:31:49 The other problem is, it can’t be cold.
0:31:55 So, I don’t know if you’ve ever tried to hydrate freeze-dried coffee with tap water.
0:31:56 It just makes clumps.
0:32:00 It doesn’t hydrate, so we actually have to warm it.
0:32:04 So, we have to build a heater into the bag system.
0:32:10 So, this is another layer of plastic that has a little circuit inside.
0:32:15 And the circuit, when you turn it on, it will warm the liquid.
0:32:17 And then it will turn color.
0:32:20 And then the medic will know, okay, I can squeeze it.
0:32:28 And all the medic has to do is tear it open, unfold the bag, wait for it to change color, squeeze it, slosh it a bit, and then hang it.
0:32:30 And that’s the way it will work.
0:32:33 That’s the user manual version of how it will work.
0:32:40 What’s the, like, 30,000-foot version of, like, just at a macro level, somebody who didn’t know what was going on?
0:32:43 Like, what would they see, and how would the world be different if this works?
0:32:47 Well, first of all, every soldier would carry this in their cargo pants.
0:32:48 Yeah.
0:32:56 So, they would have their own blood instead of a blood tag that, like, now it just says, I’m type O, I’m type whatever.
0:32:59 They actually have what they need in their pants.
0:33:07 So, if they go down, a medic can come up, take it out, and, you know, put it, you know, start resuscitating somebody.
0:33:19 It will be in every ambulance so that if somebody goes to the scene of an accident, somebody’s bleeding, they’ll be able to give them blood right away, just like they can give oxygen or CPR.
0:33:25 It will be stored in depots for mass casualty incidents.
0:33:33 So, what many people don’t know, say, for example, at the Boston Marathon bombing, they actually were running out of blood there.
0:33:37 And, unfortunately, those incidents haven’t stopped.
0:33:44 So, there will be depots around the country where there’s warehoused, shelf-stable blood.
0:33:46 It will be on cruise ships.
0:33:50 It will be in resource-limited countries like sub-Saharan Africa.
0:33:52 It will be on the space station.
0:33:54 It will be on the mission to Mars.
0:33:58 It will be wherever it’s hard to get blood.
0:34:03 We’ll be back in a minute with the lightning round.
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0:34:47 Imagine that you’re on an airplane and all of a sudden you hear this.
0:34:55 Attention passengers, the pilot is having an emergency and we need someone, anyone, to land this plane.
0:34:56 Think you could do it?
0:35:03 It turns out that nearly 50% of men think that they could land the plane with the help of air traffic control.
0:35:06 And they’re saying like, okay, pull this, do this, pull that, turn this.
0:35:07 It’s just…
0:35:08 I can do it with my eyes closed.
0:35:09 I’m Manny.
0:35:09 I’m Noah.
0:35:10 This is Devin.
0:35:16 And on our new show, No Such Thing, we get to the bottom of questions like these.
0:35:19 Join us as we talk to the leading expert on overconfidence.
0:35:26 Those who lack expertise, lack the expertise they need to recognize that they lack expertise.
0:35:29 And then as we try the whole thing out for real.
0:35:30 Wait, what?
0:35:32 Oh, that’s the runway.
0:35:33 I’m looking at this thing, see?
0:35:40 Listen to No Such Thing on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
0:35:44 Okay, lightning round.
0:35:46 What’s your second favorite type of blood cell?
0:35:49 As opposed to red blood cells?
0:35:52 I’m assuming, I’m presuming that red blood cells are your favorite.
0:35:53 Right.
0:35:54 Yeah.
0:35:56 The juvenile red blood cells.
0:35:59 The red cell, the cells that make red blood cells.
0:36:00 Okay, third favorite.
0:36:00 Third favorite.
0:36:01 Yeah, sorry.
0:36:04 Well, I’d say platelets are pretty important.
0:36:06 And they’re far more complicated than red blood cells.
0:36:10 But no platelets, and we just bleed to death.
0:36:13 So platelets are very important and fascinating.
0:36:17 The whole, like, clotting cascade thing seems wild, right?
0:36:23 Because you want the blood to clot when it needs to clot, but you really don’t want it to clot when it’s not supposed to clot, right?
0:36:26 Like, that’s such a high-stakes equilibrium.
0:36:30 It’s an amazing system, and amazing that it works when it does.
0:36:35 But, yes, clotting system is incredible and very, very complicated.
0:36:39 What’s one thing you wish we understood about blood that is still a mystery?
0:36:41 Why?
0:36:43 We have to keep remaking it.
0:36:47 So, you know, we have to renew red blood cells every three months.
0:36:50 They don’t last very long.
0:36:54 We live with the neurons that we started with as a baby.
0:36:59 But the red cells you had in the spring, they’re all gone.
0:37:01 Every last one of them is gone.
0:37:08 So you turn over all of your red blood cells, and it’s incredible that we actually do that.
0:37:14 Because it’s a huge part of our, quote, budget in terms of energy and nutrition.
0:37:18 It would be a huge evolutionary advantage in a world of scarce food, presumably.
0:37:21 So there must be some reason that it doesn’t work.
0:37:21 Right.
0:37:23 Yeah, but we don’t know.
0:37:29 What’s one common misconception that laypeople have about blood?
0:37:31 That it’s not alive.
0:37:32 Uh-huh.
0:37:35 It’s as alive as your brain.
0:37:39 And people forget, your blood is a living tissue.
0:37:40 It’s just a liquid organ.
0:37:41 Uh-huh.
0:37:45 And it’s alive, and it’s constantly doing things.
0:37:47 It’s very, very sensitive.
0:37:55 It responds perfectly to, you know, when you need to increase oxygen delivery or reduce it.
0:37:56 It can clot.
0:37:58 It can fight infection.
0:38:04 It has a lot of functions, and people just think, well, it’s just, you know, like motor oil.
0:38:08 But it’s very sophisticated.
0:38:12 What’s your view on nominative determinism?
0:38:14 Nominative determinism.
0:38:18 So, are we what we call ourselves?
0:38:19 Is that a good idea?
0:38:19 Yes.
0:38:22 I’m frankly surprised that you have not heard that phrase.
0:38:23 I’ll be honest with you.
0:38:23 Yeah.
0:38:24 So, my last name.
0:38:27 So, I fought it for a long time.
0:38:27 Yeah.
0:38:30 In fact, wanted to become a marine biologist.
0:38:33 Jacques Cousteau was my idol when I was growing up.
0:38:38 And, but, you know, I succumbed and went to medical school.
0:38:40 And actually quite happy that I did.
0:38:53 Dr. Alan Docter is a professor of pediatrics and bioengineering at the University of Maryland.
0:38:57 And he’s the co-founder and chief scientific officer of Calocyte.
0:39:02 Please email us at problem at Pushkin dot FM.
0:39:04 We are always looking for new guests for the show.
0:39:09 Today’s show was produced by Trina Menino and Gabriel Hunter Chang.
0:39:14 It was edited by Alexander Gerriton and engineered by Sarah Bruggera.
0:39:17 I’m Jacob Goldstein and we’ll be back next week with another episode of What’s Your Problem?
0:39:34 Why are TSA rules so confusing?
0:39:35 You got a hoodie on?
0:39:36 Take it off!
0:39:37 I’m Manny.
0:39:38 I’m Noah.
0:39:38 This is Devin.
0:39:43 And we’re best friends and journalists with a new podcast called No Such Thing, where
0:39:45 we get to the bottom of questions like that.
0:39:46 Why are you screaming at me?
0:39:48 Well, I can’t expect what to do.
0:39:50 Now, if the rule was the same.
0:39:51 Go off on me.
0:39:51 I deserve it.
0:39:52 You know, lock him up.
0:39:58 Listen to No Such Thing on the iHeartRadio app, Apple Podcasts, or wherever you get your
0:39:58 podcasts.
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0:00:22 Why are TSA rules so confusing?
0:00:24 You got a hoodie, I’ll take it off!
0:00:25 I’m Manny.
0:00:25 I’m Noah.
0:00:26 This is Devin.
0:00:31 And we’re best friends and journalists with a new podcast called No Such Thing,
0:00:33 where we get to the bottom of questions like that.
0:00:34 Why are you screaming at me?
0:00:36 I can’t expect what to do.
0:00:39 Now, if the rule was the same, go off on me.
0:00:39 I deserve it.
0:00:40 You know, lock him up.
0:00:43 Listen to No Such Thing on the iHeart Radio app,
0:00:46 Apple Podcasts, or wherever you get your podcasts.
0:00:48 No Such Thing.
0:00:56 Pushkin.
0:01:06 Every year, 60,000 people in the United States and 2 million people around the world
0:01:09 die because of blood loss.
0:01:14 They get in a car accident or they get shot and they bleed to death.
0:01:18 These people tend to be relatively young and healthy,
0:01:21 and a lot of them could be saved if they were quickly given blood.
0:01:25 But outside the body, blood doesn’t travel well.
0:01:26 It’s bulky.
0:01:27 You have to keep it cold.
0:01:33 And as a result, it’s hard to get blood to patients when they urgently need it.
0:01:36 Ambulances don’t tend to carry it.
0:01:38 Field medics don’t typically have it in combat.
0:01:41 And so there’s long been this dream.
0:01:47 What if we could come up with a way to make blood easier to store and transport?
0:01:54 What if we could have blood ready to go every time an ambulance gets to a car accident and a medic gets to a wounded soldier?
0:02:11 I’m Jacob Goldstein, and this is What’s Your Problem, the show where I talk to people who are trying to make technological progress.
0:02:13 My guest today is Alan Docterr.
0:02:17 He’s the co-founder and chief scientific officer at CaliSite.
0:02:19 Alan’s problem is this.
0:02:27 Can you make something like freeze-dried blood that can be rehydrated and given to patients when and where they need it?
0:02:30 Alan didn’t start out wanting to found a company.
0:02:33 He was a doctor taking care of kids in the hospital.
0:02:47 So the type of medicine I do is intensive care medicine, and for children, looking after children in the hospital who have severe infections or major injuries, and they’re critically ill.
0:02:51 And most of them are in a condition we call shock.
0:02:59 And the problem with shock is that you’re not effectively getting blood and oxygen where it’s needed.
0:03:00 Okay.
0:03:05 So people get sick and die, even though we fix the underlying problem.
0:03:16 So we can cure the infection, we repair the hole in the blood vessel, and people still, we lose them because, you know, their circulatory system is failing.
0:03:21 You know, that was frustrating, and I was interested in that problem, and I was trying to understand why that happened.
0:03:32 And what we were able to learn is there’s a traffic control system in our circulatory system that routes blood where it needs to go.
0:03:36 And red blood cells are the traffic lights.
0:03:42 So they turn green and they open up the blood vessels, or they turn red and close them.
0:03:44 And it’s very coordinated.
0:03:47 It’s a very exquisitely tuned system.
0:03:50 And I was studying that system.
0:03:50 Huh.
0:03:56 That’s governed by the way hemoglobin interacts with other chemicals in our bloodstream.
0:04:05 And it turns out it’s highly relevant for shock and fixing shock, but it turns out it’s also relevant for transfusion.
0:04:08 And that’s when this story started.
0:04:18 So you’re studying red blood cells and hemoglobin, which are obviously hemoglobin are the molecules that transport oxygen, right, that do that key function of blood.
0:04:26 That is the thing in particular that you want to replace when somebody gets shot or gets in a car accident, right, of all the things in your blood.
0:04:31 The thing you need urgently that minute is hemoglobin to deliver the oxygen, right?
0:04:41 People had known that part for a long time and had tried to develop blood substitutes in particular to solve this acute kind of trauma-setting problem.
0:04:43 But it had gone badly, right?
0:04:55 So tell me about the history up until that point of people trying to come up with ways to, you know, get hemoglobin to people in emergencies, do sort of hemoglobin replacements.
0:04:58 Well, they did the first obvious thing.
0:05:05 So the problem is you have to make the blood shelf stable in order to use it outside of hospitals.
0:05:07 So you have to get rid of the cold chain.
0:05:13 The reason we need the cold chain is the hemoglobin is inside a red blood cell.
0:05:17 The red blood cell is alive and it needs glucose.
0:05:19 It needs all kinds of things.
0:05:26 And it has to be kept cold or it goes bad, sort of like the way milk has to be kept cold or it goes bad.
0:05:31 And you can’t leave it outside the fridge too long or you can’t drink it.
0:05:32 Same thing with blood.
0:05:39 So they say, okay, if we just take the hemoglobin out of the red cell, will it still capture and release oxygen?
0:05:41 Yes, it will.
0:05:42 So far, so good.
0:05:43 So far, so good.
0:05:47 Does it need to be kept cold in order to work?
0:05:49 No, it doesn’t.
0:05:51 So it’s shelf stable.
0:05:55 Does it work if we put it inside animals?
0:05:57 Pretty much it does.
0:06:01 And so everybody’s like, okay, let’s try this.
0:06:03 And it was a catastrophe.
0:06:05 So it wasn’t just ineffective.
0:06:07 It was harmful.
0:06:09 So it was more harmful than the controls.
0:06:15 So it caused heart attacks and strokes and death in the people that got the blood.
0:06:17 Why is it bad to give people hemoglobin?
0:06:20 That is a surprising outcome, right?
0:06:22 It’s not like it’s some novel molecule.
0:06:24 It’s our bodies are full of hemoglobin.
0:06:25 All right.
0:06:28 So what it meant was we didn’t understand something.
0:06:33 It turns out hemoglobin does more than just interact with oxygen.
0:06:36 It interacts with other chemicals in the bloodstream.
0:06:44 So the hemoglobin has to be sheathed inside a membrane, and it sequesters the hemoglobin from
0:06:49 everything else in the bloodstream, from the blood vessels, the cells that line the blood
0:06:55 vessel, from the chemicals in the bloodstream, where it won’t do things it’s not supposed
0:06:55 to do.
0:07:01 And it turns out that when hemoglobin is free in the bloodstream, the blood vessels don’t
0:07:06 know whether to open or close, and what they end up doing is mostly closing.
0:07:06 Uh-huh.
0:07:11 So that’s why people who got just naked hemoglobin had heart attacks, basically.
0:07:12 Exactly.
0:07:12 Yeah.
0:07:13 Yeah.
0:07:13 Exactly.
0:07:14 Got it.
0:07:14 So, okay.
0:07:16 So this is the context, right?
0:07:22 So it’s clear, bad idea to just give people hemoglobin, alas.
0:07:23 Well, it was a good idea at the time.
0:07:26 It seemed like a good idea, but it became clear that it had been a bad idea.
0:07:28 It’s scary, in fact, right?
0:07:28 It’s scary.
0:07:30 Like so many things we’ve all done.
0:07:33 Yeah, yeah, no, no shade on the people who tried it.
0:07:37 It’s just, it’s a terrible outcome that nobody would have wanted.
0:07:45 So you, meanwhile, are studying hemoglobin, and then a chemical engineer comes to you with
0:07:45 an idea, right?
0:07:46 Tell me about that.
0:07:48 2010, what happened?
0:07:54 Yeah, I’m just studying regular red blood cells and this routing problem, right?
0:07:54 Which I understood.
0:08:01 That’s why, you know, a lot of these blood substitutes, what we call the unencapsulated
0:08:02 hemoglobins, failed.
0:08:06 People started to understand that, but I wasn’t thinking like, oh, I know how to solve that
0:08:07 problem.
0:08:11 I was minding my own business doing something completely different.
0:08:18 The chemical engineer, the bioengineer, was making special particles, nanoparticles for
0:08:18 imaging.
0:08:27 So there’s a new form of medicines and therapies where you make little fat droplets, and you
0:08:33 can decorate them with all kinds of molecules that either home to different parts of your
0:08:35 body, and you can see them on x-ray.
0:08:37 You can put drugs inside.
0:08:39 You can do all kinds of things with them.
0:08:44 Well, just to be clear, these fat droplets, as you’re describing them, like, they were the
0:08:48 technology used to encapsulate the COVID vaccines, right?
0:08:48 That’s right.
0:08:53 The RNA COVID vaccines were in, well, lipid nanoparticle is the jargon, right?
0:08:54 Although I like fat droplets.
0:08:54 Exactly.
0:08:55 I appreciate fat droplets.
0:09:02 So yeah, liposome was used for, or a fat droplet was used for the COVID vaccine, and it’s
0:09:03 used for other things, too.
0:09:14 So what Dr. Pan, Depanjan Pan, brilliant chemical engineer, so he was making particles so that you
0:09:15 could see specific things.
0:09:18 So you want to be able to see breast cancer.
0:09:20 You want to be able to see a blood clot.
0:09:23 You want to see, you know, a particular type of cell.
0:09:30 Then you put something on a fat droplet that finds that cell, and you put a little metal in
0:09:34 the droplet that you can see with a special CT scan.
0:09:41 And then say, suddenly, I see very small and tiny, hard-to-detect cancers, and so on.
0:09:47 And so he was making these particles, and he was doing them in a way he wanted to make a lot of
0:09:52 surface area, and he ended up making particles that looked like red blood cells.
0:09:52 Huh.
0:09:54 Just by happenstance.
0:09:58 He just looked at one and said, hey, I know what that looks like, a red blood cell.
0:10:04 So red blood cells are also trying to have a lot of surface area because they exchange gas.
0:10:10 And he was trying to create a lot of surface area for a different reason, so he could decorate the
0:10:11 particles with these proteins.
0:10:16 I was looking at red blood cells today, trying to think of what they look like, and I thought of
0:10:24 biali, which is kind of a niche analogy, like a bagel, but with a thin, doughy part in where the hole would be.
0:10:27 Do you have a go-to description of a red blood cell?
0:10:28 That’s what we use.
0:10:30 They’re called nano-bialis.
0:10:31 Oh, no kidding.
0:10:31 Yes.
0:10:32 Okay.
0:10:35 Or the other word, people say, a biconcave disc.
0:10:38 Yeah, that’s less salient.
0:10:38 Less cool.
0:10:39 That’s right.
0:10:39 Okay.
0:10:42 So does he come to you with this idea?
0:10:43 Right.
0:10:44 So what happens?
0:10:46 He’s like, oh, that looks like a red blood cell.
0:10:46 What does he do?
0:10:51 So he thought, hey, I wonder if I could put hemoglobin inside.
0:10:52 Uh-huh.
0:10:59 And he was loosely familiar with the problems with auction carriers, and he says, I wonder
0:11:01 if I could just put hemoglobin inside.
0:11:04 And he figured out how to do that.
0:11:08 And then he’s like, oh, I don’t know how to tell if this works or not.
0:11:15 So we’re both at WashU, and WashU has this collaboration website where you can Google, or it’s like Googling,
0:11:18 that it’s just at WashU, the university.
0:11:18 Oh, interesting.
0:11:21 Like an internal search engine.
0:11:21 Uh-huh.
0:11:21 Yeah.
0:11:27 So he searched red blood cell physiology, and I popped up.
0:11:33 And so he called me and told me the story and said, you know, why don’t you come over to
0:11:39 my lab, and I’d like to show you what we’re doing and see if this works, and maybe we could
0:11:41 figure out how to collaborate.
0:11:43 Well, it didn’t work.
0:11:44 Huh.
0:11:44 But-
0:11:46 Wait, what do you mean it didn’t work?
0:11:46 It didn’t work.
0:11:47 I was all ready for it to work.
0:11:48 What happened?
0:11:48 Yeah.
0:11:55 Well, there’s a little more to it than just putting hemoglobin inside a fat droplet.
0:11:55 Yeah.
0:12:02 So what I realized is, conceptually, this would solve the problem that the unencapsulated
0:12:07 hemoglobins were plagued by, that this were like little red blood cells.
0:12:14 And if we could figure out the chemistry to make this capture and release oxygen, that maybe
0:12:16 this would, you know, make things safe.
0:12:18 And you can freeze dry these things.
0:12:23 So they could be, you know, shelf stable and very lightweight.
0:12:26 So it’s like instant coffee, but for red blood cells.
0:12:27 That’s the dream.
0:12:28 Yeah.
0:12:29 Yeah, exactly.
0:12:36 So initially it doesn’t work, but you realize that the idea is fundamentally plausible.
0:12:43 So like, what are the things you have to sort of figure out, make work for this to work?
0:12:48 A number of things from the inside out.
0:12:48 Okay.
0:12:53 So first of all, you’ve got a droplet that has hemoglobin inside it.
0:13:00 Hemoglobin, the reason red blood cells work, they’re a lot more than just bags of hemoglobin.
0:13:03 They have lots of other functions.
0:13:08 And so we had to decide, what are we going to keep and what do we get rid of?
0:13:11 Because you can’t build the whole red blood cell.
0:13:12 We don’t know how to do that.
0:13:13 It’s crazy.
0:13:16 You want to do as little as you can get away with, right?
0:13:17 Right.
0:13:21 You want the stripped down basic thing.
0:13:23 And so it just has to transport oxygen.
0:13:27 And then it has to not do a bunch of other things.
0:13:29 We don’t want it to cause trouble either.
0:13:34 Well, and subtly, subtly, when you say transport oxygen, it has to know when to pick up oxygen
0:13:39 from the lungs and has to know when to release oxygen to whatever tissue needs it, right?
0:13:43 Like, that part seems hard from the outside.
0:13:44 Right.
0:13:45 Well, they’re opposites.
0:13:46 Yeah.
0:13:47 Yeah.
0:13:49 And it has to do it at the right time, right?
0:13:50 It has to do it in the right setting.
0:13:51 Yeah.
0:13:53 At the right speed.
0:13:53 Yeah.
0:13:56 So, yeah, it’s all very finely tuned inside our body.
0:14:00 So we had to try to imitate the behavior of a real red cell.
0:14:01 Yeah.
0:14:08 So, and the real red cell has, people understand like, okay, there are these other molecules
0:14:15 inside red cells that modify the way the hemoglobin interacts with oxygen that causes it to capture
0:14:21 oxygen effectively in the lung and then let go when it gets out in tissue.
0:14:21 Okay.
0:14:25 And the red cells responding, the red cell doesn’t know, oh, I’m in the lung.
0:14:27 Oh, I’m in the lip.
0:14:29 I’m in the muscle.
0:14:29 Right.
0:14:34 So it’s looking for cues.
0:14:34 Yeah.
0:14:41 So it doesn’t have a map, but it can almost smell where it is because of the chemicals that are
0:14:44 different in the lung than in exercising muscle.
0:14:51 So, and it’s primarily responding to the amount of acid and the amount of carbon dioxide that’s
0:14:52 in the blood.
0:15:02 And so what we did is we created responsive elements that would work like red cells, but in a different
0:15:09 way so that they would change their shape or change their ability to interact with other
0:15:15 molecules in response to those two signals, carbon dioxide and acid.
0:15:22 So then the artificial red cell, quote, knows it’s in the lung or knows it’s in the muscle.
0:15:24 So we call that wet wear.
0:15:31 So it’s like a thousand little thermostats inside each little particle.
0:15:34 And it’s telling the hemoglobin what to do.
0:15:37 I’m sure there are a lot of hard parts, but that sounds like the hard part.
0:15:40 Well, that was, yeah, that was one of the hard parts, right?
0:15:44 Then we have to make it silent to the immune system.
0:15:48 So our body doesn’t recognize it.
0:15:52 We have to make sure that it doesn’t alter the viscosity of blood.
0:15:55 So it doesn’t get too thick or too thin.
0:16:00 And then we have to make sure it doesn’t interact with the blood clotting system.
0:16:03 It doesn’t cause blood clots or interfere with blood clots.
0:16:06 And then we have to make it freeze dry.
0:16:13 And then, you know, we have to make it circulate for a long time.
0:16:19 We have to evade the body system for clearing things that shouldn’t be in our blood out of our blood.
0:16:25 And so once we solve all those things, you know, then, you know, now it’s working in an animal model.
0:16:35 And that’s why the very first one didn’t work, because while Dr. Pan had already figured out how to get hemoglobin inside the fat droplet, it didn’t do any of these other things yet.
0:16:39 So is there a moment when you decide, oh, we should start a company?
0:16:40 Yes.
0:16:50 And so we started the company when we had first demonstrated proof of concept that we could create an artificial red cell.
0:16:53 At that point, we have a different task.
0:17:00 So the original academic task was, can we design an artificial cell?
0:17:02 Can we prove that it works?
0:17:10 Once we’d done that, we now have a development, commercial development task, which is, can we make it reliably?
0:17:12 Can we make it over and over again?
0:17:13 Can we make a lot of it?
0:17:20 Can we make sure that it passes all the safety and efficacy criteria at FDA?
0:17:23 So that task, we need a company for.
0:17:25 It’s very different than a university task.
0:17:28 And that’s when we formed Kalosite in order to do those things.
0:17:34 We’ll be back in just a minute.
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0:18:35 It turns out that nearly 50% of men think that they could land the plane with the help of air traffic control.
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0:19:21 Write that in 2023, you got a $46 million DARPA grant, or were part of that.
0:19:21 Tell me about that.
0:19:24 That seems like a big moment in the history of this project.
0:19:25 That was the moment, yeah.
0:19:27 I have to say.
0:19:34 So, we had been working on, in a reasonably successful way, developing the red blood cells, artificial red cells.
0:19:38 But what DARPA wanted, DARPA wanted everything.
0:19:41 They wanted all the function of blood.
0:19:44 So, the ability to clot.
0:19:51 So, for a soldier, basically, if you need artificial red cells, it’s because you’re bleeding.
0:19:52 By definition.
0:20:03 If you just replace the red cells, and you don’t replace the clotting factor, then it’s like pouring blood into a sieve.
0:20:05 It just falls back out again.
0:20:07 It’s ineffective.
0:20:11 So, they realize that we need to be able to replace everything.
0:20:15 And to do that, at the point of injury, you need freeze-dried plasma.
0:20:17 You need freeze-dried platelets.
0:20:19 You need freeze-dried red cells.
0:20:21 And it has to be scalable.
0:20:24 And, you know, there are a lot of logistic concerns.
0:20:33 So, if they put out a call for applications for teams to form from the people who are working on each of those components,
0:20:47 And everybody had just been working on them separately, to come together and form a consortium that would figure out how to make all these different components compatible and equivalent to stored blood.
0:20:53 So, we built a consortium to do that, and we competed effectively to win that award.
0:20:58 What is the status of the, what do you call it, artificial whole blood?
0:20:59 What do you call the whole package?
0:21:02 Unfortunately, we don’t have a very sexy name for it yet.
0:21:04 We call it the whole blood analog.
0:21:10 So, you know, it’s not completely artificial because it’s a biologically derived plasma.
0:21:13 It’s just regular plasma that’s been freeze-dried.
0:21:13 Okay.
0:21:15 The platelets are fully synthetic.
0:21:19 So, they help, you know, form blood clots.
0:21:20 To stop the bleeding.
0:21:24 To stop the bleeding, which is, you know, that’s why they’re getting this material.
0:21:24 Yeah.
0:21:28 And so, we sort of have two threads going now, right?
0:21:34 There’s how is it going on your artificial red blood cells, and then how is the whole blood analog project going?
0:21:35 So, let’s just take those in order.
0:21:43 Like, what is the status of the, like, are you testing the artificial red blood cell on its own in clinical trials?
0:21:45 Is that part of the plan, to do that by itself?
0:21:47 Or do you, does it need to be the whole package?
0:21:50 Well, it has to be tested by itself first.
0:21:51 Yeah.
0:21:55 And so, it’s a standalone element.
0:21:59 And so, we are still in what’s called preclinical testing.
0:22:02 So, we’re testing in animal models.
0:22:14 And in parallel, we’re developing the combined product, which will be sequentially administered plasma, O2 carrier, and platelet.
0:22:17 And that’s also in preclinical testing.
0:22:19 The O2 carrier is the red blood cell, is what you’re making.
0:22:20 Is the red blood cell.
0:22:21 That’s right.
0:22:23 And plasma and platelet.
0:22:26 And that is expected that will follow.
0:22:32 So, we have to first test each element by itself before we start mixing cocktails.
0:22:34 That’s so hard.
0:22:43 Like, I feel like the way fractional probabilities work, if a bunch of things have to work separately, and there’s some, you know, the fractions multiply, right?
0:22:47 So, it gets less and less likely that it will work, just probabilistically.
0:22:47 Right.
0:22:52 But what we have the ability to do is adapt to what we find.
0:22:52 Yeah.
0:22:54 And that’s what we’ve had to do.
0:22:58 So, we took these components and, of course, they didn’t automatically work all together.
0:23:05 So, we weren’t able to just take the red blood cells and the plasma and the platelets and just put them in a blender and get blood.
0:23:07 So, we’ve had to tune.
0:23:17 We’re actually now on version 4.12 of the, starting with version 0 of the system.
0:23:19 Of the whole blood, of the whole blood analog.
0:23:20 Yes.
0:23:20 Yeah.
0:23:20 Okay.
0:23:23 And is it right that there are other groups?
0:23:26 Is there a group in Japan working on something similar?
0:23:30 Tell me about that and tell me about the field more broadly, other similar projects.
0:23:30 Sure.
0:23:43 The other main encapsulated program is in Japan, led by a really successful scientist named Hiromi Sakai.
0:23:52 He’s been working on this for over a decade, developing another, it’s very, it’s essentially the same concept.
0:23:55 It’s a liposome with hemoglobin on the inside.
0:23:56 A fat droplet.
0:23:57 A fat droplet.
0:23:58 Yeah.
0:23:58 Right.
0:23:59 It’s a fat droplet.
0:23:59 Yeah.
0:24:01 And it’s a little different.
0:24:04 It doesn’t have that wet wear system that we talked about.
0:24:05 Okay.
0:24:10 He has adjusted the oxygen affinity to be sort of in the middle.
0:24:15 So, it’s pretty good at capturing oxygen in the lung and pretty good at letting it go.
0:24:19 And tissue, it doesn’t shift up and down depending on where it is.
0:24:21 So, it’s good enough.
0:24:22 It works.
0:24:25 And he’s already begun to test its safety in humans.
0:24:27 Now, it’s not freeze-dried.
0:24:29 It’s still in water.
0:24:29 Okay.
0:24:34 And they are not working on combining it with plasma and platelets.
0:24:35 It’s just the O2 carrier.
0:24:39 How do you think it’s going, the Japanese version?
0:24:40 Great.
0:24:41 They’re out in front.
0:24:42 Yeah.
0:24:48 So, they’ve tested in humans and they had some minor issues that I think have been probably
0:24:49 been addressed.
0:24:51 And it’s incredibly exciting.
0:24:54 We’re all benefiting from Dr. Sakai’s leadership.
0:24:59 So, to return to your own work and the work of the consortium that you’re part of, what’s
0:25:00 the happy story?
0:25:05 Like, how long in the future do you think about and what do you think about when you think about
0:25:05 it going well?
0:25:13 So, if you think about it going well, I guess there’s a presumption baked into that question.
0:25:17 Mostly, I think about, you know, how it’s not going to go well.
0:25:18 Okay.
0:25:19 Well, how might it not go well?
0:25:23 I mean, I guess that one’s easier to imagine in some ways, but how might it not go well?
0:25:27 I mean, what I’m really worried about is the things I can’t imagine.
0:25:31 So, the things we imagine, we’re constantly trying to think of how it won’t go well and
0:25:34 we try to anticipate a solution to the problem.
0:25:36 And fix it.
0:25:40 The things that we can’t plan for, of course, are the things that we don’t yet understand.
0:25:42 The Rumsfeldian unknown unknowns.
0:25:43 Yeah.
0:25:44 You beat me to it.
0:25:44 Yeah.
0:25:45 Yeah.
0:25:51 So, and that happens monthly, where it’s like, oh, we didn’t think of that.
0:25:53 Now we have to solve a new problem.
0:25:53 Yeah.
0:25:55 Because we’re off the map.
0:25:58 You know, we don’t really, nobody’s been here before.
0:26:01 So, we have to figure those things out.
0:26:03 Does it seem impossibly hard?
0:26:08 Like, frankly, this one, this project just seems so hard.
0:26:09 Right.
0:26:09 It is hard.
0:26:12 If it were easy, it’d be done already.
0:26:17 But the wonderful thing is that I think that we have all the tools that we need to solve
0:26:18 the problem now.
0:26:24 The advances in synthetic chemistry are impossible to overstate.
0:26:32 The advances in nanomedicine and nanofabrication are, you know, allowing us to respond in very
0:26:33 quick ways.
0:26:39 The ability to use machine learning and artificial intelligence to improve our design is reducing
0:26:42 the need to do thousands and thousands of experiments.
0:26:48 So, we can use the computers to tell us the likely things to work.
0:26:51 And it reduces the empiric burden.
0:27:01 And we’ve got great resources because the NIH and Department of Defense, DARPA, have put a lot
0:27:02 of resources in our hands.
0:27:11 So, we’re very fortunate in that we can very quickly respond to the problems that we encounter.
0:27:15 So, it works very effectively in the models that we have.
0:27:18 But now, we also have to make this scalable.
0:27:21 So, that’s another huge challenge.
0:27:27 So, we have to go from making what you might call craft beer to Budweiser.
0:27:31 And just to be clear, it’s made from real blood, right?
0:27:36 Like, the hemoglobin in your lipid nanoparticles is hemoglobin from people, right?
0:27:38 It’s not synthesized.
0:27:40 So, that is a scale challenge right there, right?
0:27:42 That’s impossible, right?
0:27:46 So, we can’t synthesize hemoglobin from amino acids.
0:27:49 That is beyond our current capability.
0:27:54 But we can program other organisms to make it for us.
0:27:55 Like yeast?
0:27:56 Ideally yeast, right?
0:27:57 Put it in a vat?
0:27:57 That’s right.
0:27:58 Is that the…
0:27:58 Yeah.
0:28:00 Yeah, we’re going to brew it.
0:28:07 So, we have a yeast project where we are training yeast to make human hemoglobin and to secrete it.
0:28:07 Yeah.
0:28:10 And that will eventually be our source.
0:28:11 So, okay.
0:28:16 So, take 30 seconds off of thinking about all the things that can go wrong and that you have to figure out.
0:28:24 And just tell me if someday you or the people who come after you, even, respectfully, figure out how to do all the things you’re trying to do.
0:28:25 What will it look like?
0:28:30 Well, we actually, believe it or not, have done that.
0:28:34 We have a prototype of the delivery system.
0:28:41 We’ve been simultaneously trying to work with the people who would be using it so that we don’t end up with an end product.
0:28:44 And they say, but did you think about yeast?
0:28:44 Yeah, yeah, yeah.
0:28:46 And we’re just like, uh-oh, no.
0:28:50 So, a person gets in a car accident or a soldier gets shot on the battlefield.
0:28:54 What happens in this future where the thing you’re working on works?
0:28:57 So, what they’ll have is a kit.
0:29:00 And in the kit will be three components.
0:29:03 The O2 carrier, the plasma, and the platelet.
0:29:05 All of them will be dry powders.
0:29:06 Okay.
0:29:13 So, the instructions that we got from the Department of Defense were, it has to work in the dark, in a ditch, under fire.
0:29:14 Ah, okay.
0:29:19 And it has to be usable by somebody who has basically no medical training.
0:29:19 Yeah.
0:29:25 So, that’s basically, you know, not a sophisticated nurse or a scientist.
0:29:27 Basically, they want you to make instant coffee, but for blood.
0:29:32 But for blood, but also, it’s instant coffee is too complicated.
0:29:39 You’ve got to heat the water, you’ve got to dispense it from a jar into a cup and pour the water.
0:29:41 You can’t do any of that.
0:29:51 So, what we have is a system that has a split bag with a dry side and a wet side, and something called a weak weld.
0:29:55 So, when it’s folded over, you can stand on it, and it won’t open.
0:30:07 But when you unfold it, you squeeze it, and it pops, and the water migrates from one side to the other and hydrates the dry material.
0:30:08 Okay.
0:30:16 And then it sloshes around in there for about a minute, and then you hang it, and you can use it just like a unit of blood.
0:30:17 Right.
0:30:21 You hang it like a bag that goes into your arm on an IV when you’re at the hospital.
0:30:26 And there’s one like that for the plasma, and the platelet’s a little different because it’s a much smaller volume.
0:30:29 That eventually will be what’s called an auto-injector.
0:30:31 Everybody’s seen EpiPens.
0:30:31 Yeah.
0:30:33 So, it’ll be like an EpiPen.
0:30:35 Now, there’s an additional problem.
0:30:36 Damn.
0:30:37 Yes.
0:30:40 There’s two other problems, really.
0:30:47 So, one is, for it to be shelf-stable, it can’t interact with oxygen in the air.
0:30:48 Uh-huh, uh-huh.
0:30:53 So, water and iron and oxygen equals rust.
0:30:57 Yeah, when you think about hemoglobin, it seems like rust, right?
0:31:00 Hemoglobin, it’s iron in the hemoglobin that is binding to the oxygen, right?
0:31:04 And I’m like, wait, is hemoglobin just rusting all the time in my blood?
0:31:04 It is.
0:31:07 In fact, right now, your hemoglobin is rusting.
0:31:11 About 10% of it is rusting constantly.
0:31:15 But you have a rust remover inside your red blood cells.
0:31:24 That is, every time it goes around, there’s a little molecule in there that’s scrubbing the rust and polishing the iron.
0:31:28 So, we have to prevent that from happening during storage.
0:31:35 And to do that, we have to have a plastic, soft plastic, but that has glass-like properties.
0:31:38 So, it doesn’t allow water or oxygen through it.
0:31:45 And so, that’s a very novel film that we are applying for the first time to blood storage.
0:31:49 The other problem is, it can’t be cold.
0:31:55 So, I don’t know if you’ve ever tried to hydrate freeze-dried coffee with tap water.
0:31:56 It just makes clumps.
0:32:00 It doesn’t hydrate, so we actually have to warm it.
0:32:04 So, we have to build a heater into the bag system.
0:32:10 So, this is another layer of plastic that has a little circuit inside.
0:32:15 And the circuit, when you turn it on, it will warm the liquid.
0:32:17 And then it will turn color.
0:32:20 And then the medic will know, okay, I can squeeze it.
0:32:28 And all the medic has to do is tear it open, unfold the bag, wait for it to change color, squeeze it, slosh it a bit, and then hang it.
0:32:30 And that’s the way it will work.
0:32:33 That’s the user manual version of how it will work.
0:32:40 What’s the, like, 30,000-foot version of, like, just at a macro level, somebody who didn’t know what was going on?
0:32:43 Like, what would they see, and how would the world be different if this works?
0:32:47 Well, first of all, every soldier would carry this in their cargo pants.
0:32:48 Yeah.
0:32:56 So, they would have their own blood instead of a blood tag that, like, now it just says, I’m type O, I’m type whatever.
0:32:59 They actually have what they need in their pants.
0:33:07 So, if they go down, a medic can come up, take it out, and, you know, put it, you know, start resuscitating somebody.
0:33:19 It will be in every ambulance so that if somebody goes to the scene of an accident, somebody’s bleeding, they’ll be able to give them blood right away, just like they can give oxygen or CPR.
0:33:25 It will be stored in depots for mass casualty incidents.
0:33:33 So, what many people don’t know, say, for example, at the Boston Marathon bombing, they actually were running out of blood there.
0:33:37 And, unfortunately, those incidents haven’t stopped.
0:33:44 So, there will be depots around the country where there’s warehoused, shelf-stable blood.
0:33:46 It will be on cruise ships.
0:33:50 It will be in resource-limited countries like sub-Saharan Africa.
0:33:52 It will be on the space station.
0:33:54 It will be on the mission to Mars.
0:33:58 It will be wherever it’s hard to get blood.
0:34:03 We’ll be back in a minute with the lightning round.
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0:34:47 Imagine that you’re on an airplane and all of a sudden you hear this.
0:34:55 Attention passengers, the pilot is having an emergency and we need someone, anyone, to land this plane.
0:34:56 Think you could do it?
0:35:03 It turns out that nearly 50% of men think that they could land the plane with the help of air traffic control.
0:35:06 And they’re saying like, okay, pull this, do this, pull that, turn this.
0:35:07 It’s just…
0:35:08 I can do it with my eyes closed.
0:35:09 I’m Manny.
0:35:09 I’m Noah.
0:35:10 This is Devin.
0:35:16 And on our new show, No Such Thing, we get to the bottom of questions like these.
0:35:19 Join us as we talk to the leading expert on overconfidence.
0:35:26 Those who lack expertise, lack the expertise they need to recognize that they lack expertise.
0:35:29 And then as we try the whole thing out for real.
0:35:30 Wait, what?
0:35:32 Oh, that’s the runway.
0:35:33 I’m looking at this thing, see?
0:35:40 Listen to No Such Thing on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
0:35:44 Okay, lightning round.
0:35:46 What’s your second favorite type of blood cell?
0:35:49 As opposed to red blood cells?
0:35:52 I’m assuming, I’m presuming that red blood cells are your favorite.
0:35:53 Right.
0:35:54 Yeah.
0:35:56 The juvenile red blood cells.
0:35:59 The red cell, the cells that make red blood cells.
0:36:00 Okay, third favorite.
0:36:00 Third favorite.
0:36:01 Yeah, sorry.
0:36:04 Well, I’d say platelets are pretty important.
0:36:06 And they’re far more complicated than red blood cells.
0:36:10 But no platelets, and we just bleed to death.
0:36:13 So platelets are very important and fascinating.
0:36:17 The whole, like, clotting cascade thing seems wild, right?
0:36:23 Because you want the blood to clot when it needs to clot, but you really don’t want it to clot when it’s not supposed to clot, right?
0:36:26 Like, that’s such a high-stakes equilibrium.
0:36:30 It’s an amazing system, and amazing that it works when it does.
0:36:35 But, yes, clotting system is incredible and very, very complicated.
0:36:39 What’s one thing you wish we understood about blood that is still a mystery?
0:36:41 Why?
0:36:43 We have to keep remaking it.
0:36:47 So, you know, we have to renew red blood cells every three months.
0:36:50 They don’t last very long.
0:36:54 We live with the neurons that we started with as a baby.
0:36:59 But the red cells you had in the spring, they’re all gone.
0:37:01 Every last one of them is gone.
0:37:08 So you turn over all of your red blood cells, and it’s incredible that we actually do that.
0:37:14 Because it’s a huge part of our, quote, budget in terms of energy and nutrition.
0:37:18 It would be a huge evolutionary advantage in a world of scarce food, presumably.
0:37:21 So there must be some reason that it doesn’t work.
0:37:21 Right.
0:37:23 Yeah, but we don’t know.
0:37:29 What’s one common misconception that laypeople have about blood?
0:37:31 That it’s not alive.
0:37:32 Uh-huh.
0:37:35 It’s as alive as your brain.
0:37:39 And people forget, your blood is a living tissue.
0:37:40 It’s just a liquid organ.
0:37:41 Uh-huh.
0:37:45 And it’s alive, and it’s constantly doing things.
0:37:47 It’s very, very sensitive.
0:37:55 It responds perfectly to, you know, when you need to increase oxygen delivery or reduce it.
0:37:56 It can clot.
0:37:58 It can fight infection.
0:38:04 It has a lot of functions, and people just think, well, it’s just, you know, like motor oil.
0:38:08 But it’s very sophisticated.
0:38:12 What’s your view on nominative determinism?
0:38:14 Nominative determinism.
0:38:18 So, are we what we call ourselves?
0:38:19 Is that a good idea?
0:38:19 Yes.
0:38:22 I’m frankly surprised that you have not heard that phrase.
0:38:23 I’ll be honest with you.
0:38:23 Yeah.
0:38:24 So, my last name.
0:38:27 So, I fought it for a long time.
0:38:27 Yeah.
0:38:30 In fact, wanted to become a marine biologist.
0:38:33 Jacques Cousteau was my idol when I was growing up.
0:38:38 And, but, you know, I succumbed and went to medical school.
0:38:40 And actually quite happy that I did.
0:38:53 Dr. Alan Docter is a professor of pediatrics and bioengineering at the University of Maryland.
0:38:57 And he’s the co-founder and chief scientific officer of Calocyte.
0:39:02 Please email us at problem at Pushkin dot FM.
0:39:04 We are always looking for new guests for the show.
0:39:09 Today’s show was produced by Trina Menino and Gabriel Hunter Chang.
0:39:14 It was edited by Alexander Gerriton and engineered by Sarah Bruggera.
0:39:17 I’m Jacob Goldstein and we’ll be back next week with another episode of What’s Your Problem?
0:39:34 Why are TSA rules so confusing?
0:39:35 You got a hoodie on?
0:39:36 Take it off!
0:39:37 I’m Manny.
0:39:38 I’m Noah.
0:39:38 This is Devin.
0:39:43 And we’re best friends and journalists with a new podcast called No Such Thing, where
0:39:45 we get to the bottom of questions like that.
0:39:46 Why are you screaming at me?
0:39:48 Well, I can’t expect what to do.
0:39:50 Now, if the rule was the same.
0:39:51 Go off on me.
0:39:51 I deserve it.
0:39:52 You know, lock him up.
0:39:58 Listen to No Such Thing on the iHeartRadio app, Apple Podcasts, or wherever you get your
0:39:58 podcasts.
0:40:00 No Such Thing.
0:40:03 This is an iHeart Podcast.
Dr. Allan Doctor is the co-founder and chief scientific officer at Kalocyte, a company that is developing dried red blood cells that can be rehydrated and used in medical emergencies.
On today’s show, Dr. Doctor explains the complex science behind artificial blood, and how this innovation could help save millions of lives.
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