Speaker 1: Pushkin. Every year, sixty thousand people in the United States
Speaker 1: and two million people around the world die because of
Speaker 1: blood loss. They get in a car accident, or they
Speaker 1: get shot and they bleed to death. These people tend
Speaker 1: to be relatively young and healthy, and a lot of
Speaker 1: them could be saved if they were quickly given blood.
Speaker 1: But outside the body, blood doesn't travel well. It's bulky.
Speaker 1: You have to keep it cold, and as a result,
Speaker 1: it's hard to get blood to patience when they urgently
Speaker 1: need it. Ambulances don't tend to carry it. Field medics
Speaker 1: don't typically have it in combat, and so there's long
Speaker 1: been this dream. What if we could come up with
Speaker 1: a way to make blood easier to store and transport.
Speaker 1: What if we could have blood ready to go every
Speaker 1: time an ambulance gets to a car accident and a
Speaker 1: medic gets to a wounded soldier. If we could do that,
Speaker 1: we could save millions of lives. I'm Jacob Goldstein and
Speaker 1: this is What's Your Problem, the show where I talk
Speaker 1: to people who are trying to make technological progress. My
Speaker 1: guest today is Alan Doctor. He's the co founder and
Speaker 1: chief scientific officer at Kalasite. Alan's problem is this, can
Speaker 1: you make something like freeze dried blood that can be
Speaker 1: rehydrated and given to patients when and where they need it.
Speaker 1: Alan didn't start out wanting to found a company. He
Speaker 1: was a doctor taking care of kids in the hospital.
Speaker 2: So the type of medicine I do is intensive care
Speaker 2: of medicine. So this is and for children, looking after
Speaker 2: children in the hospital who have severe infections or major
Speaker 2: injuries and they're critically ill, and most of them are
Speaker 2: in something a condition we call shock. And the problem
Speaker 2: with shock is that you're not effectively getting blood and
Speaker 2: oxygen where it's needed. Okay, so people get sick and die.
Speaker 2: Even though we fix the underlying problem, so we can
Speaker 2: cure the infection, we repair the hole in the blood vessel,
Speaker 2: and people still we lose them because their circulatory system
Speaker 2: is failing.
Speaker 1: You know.
Speaker 2: That was frustrating, and I was interested in that problem
Speaker 2: and I was trying to understand why that happened. And
Speaker 2: what we were able to learn is there's a traffic
Speaker 2: control system in our circulatory system that routes blood where
Speaker 2: it needs to go, and red blood cells are the
Speaker 2: traffic lights, so they turn green and they open up
Speaker 2: the blood vessels or they turn red and close them,
Speaker 2: and it's very coordinated. It's a very exquisitely tuned system.
Speaker 2: And I was studying that, huh, that's governed by the
Speaker 2: way hemoglobin interacts with other chemicals in our blood stream.
Speaker 2: And it turns out it's highly relevant for shock and
Speaker 2: fixing shock. But it turns out it's also relevant for transfusion.
Speaker 2: And that's when this story started.
Speaker 1: So you're studying red blood cells and hemoglobin, which are
Speaker 1: obviously hemoglobin are the molecules that transport oxygen, right, that
Speaker 1: do that key function of blood. That is the thing
Speaker 1: in particular that you want to replace when somebody gets
Speaker 1: shot or gets in a car accident. Right, of all
Speaker 1: the things in your blood, the thing you need urgently
Speaker 1: that minute is hemoglobin to deliver the oxygen right. Right.
Speaker 1: People had known that part for a long time and
Speaker 1: had tried to develop blood substitutes in particular to solve
Speaker 1: this acute kind of trauma setting problem. But it had
Speaker 1: gone badly right, So tell me about the history up
Speaker 1: until that point of people trying to come up with
Speaker 1: ways to you know, get hemoglobin to people in emergencies,
Speaker 1: do sort of hemoglobin replacements.
Speaker 2: Well, they did the first obvious thing. So the problem
Speaker 2: is you have to make the bloodshelf stable in order
Speaker 2: to use it outside of hospitals, So you have to
Speaker 2: get rid of the cold chain. The reason we need
Speaker 2: the cold chain is the hemoglobin's inside a red blood cell.
Speaker 2: The red blood cell's alive, and it needs glucose, it
Speaker 2: needs all kinds of things, and it has to be
Speaker 2: kept colder. It goes bad, sort of like the way
Speaker 2: milk has to be kept colder. It goes bad, and
Speaker 2: you can't leave it outside the fridge too long or
Speaker 2: you can't drink it.
Speaker 1: The same thing with blood.
Speaker 2: So they say, okay, if we just take the hemoglobin
Speaker 2: out of the red cell, will it still capture and
Speaker 2: release oxygen?
Speaker 1: Yes, okay it will. So far, so good, So far,
Speaker 1: so good.
Speaker 2: Does it need to be kept cold in order to work, No,
Speaker 2: it doesn't, So it's shelf stable. Doesn't work if we
Speaker 2: put it inside animals. Pretty much it does, and so
Speaker 2: everybody's like, okay, let's try this.
Speaker 1: Yeah.
Speaker 2: And it was a catastrophe, so it wasn't just ineffective.
Speaker 2: It was harmful, so it was more harmful than the controls.
Speaker 2: So it caused heart attacks and strokes and death in
Speaker 2: the people that got the blood.
Speaker 1: Why is it bad to give people hemoglobin? That is
Speaker 1: a surprising outcome, right, It's not like it's some novel molecule.
Speaker 1: It's our bodies are full of hemoglobin, all right.
Speaker 2: So what it meant was we didn't understand something. It
Speaker 2: turns out hemoglobin does more than just interact with oxygen.
Speaker 2: It interacts with other chemicals in the blood stream. So
Speaker 2: the hemoglobin has to be sheathed inside a membrane, and
Speaker 2: it sequesters the hemoglobin from everything else in the blood stream,
Speaker 2: from the blood vessels, the cells that line the blood vessel,
Speaker 2: from the chemicals in the bloodstream where it won't do
Speaker 2: things it's not supposed to do. And it turns out
Speaker 2: that when hemoglobin is free in the bloodstream, the blood
Speaker 2: vessels don't know whether they're to open or close, and
Speaker 2: what they end up doing is mostly closing.
Speaker 1: Uh huh. So that's why people who got just naked
Speaker 1: hemoglobin had heart attacks. Basically exactly, yeah, exactly, got it.
Speaker 1: So okay, So this is the context, right, So clear
Speaker 1: bad idea to just give people hemoglobin. Alas well, it
Speaker 1: was a good idea. It seemed like a good idea,
Speaker 1: but it became clear that it had been a bad idea.
Speaker 1: It's scary in fact, right, it scary like so many
Speaker 1: things we've all done. Yeah, yeah, no, no, no shade
Speaker 1: on the people who tried it. It's just a it's
Speaker 1: a terrible outcome that nobody would have wanted. So you meanwhile,
Speaker 1: are studying hemoglobin and then a chemical engineer comes to
Speaker 1: you with an idea, Right, tell me about that. Twenty
Speaker 1: ten what happened?
Speaker 2: Yeah, I'm just studying regular red blood cells and this
Speaker 2: routing problem, right, which I understood. That's why you know
Speaker 2: a lot of these blood substitutes, what we call the
Speaker 2: unencapsulated hemoglobins failed. People started to understand that, but I
Speaker 2: wasn't thinking like, oh, I know how to solve that problem.
Speaker 2: I was minding my own business doing something completely different.
Speaker 2: The chemical engineer, the bioengineer was making special particles, nanoparticles
Speaker 2: for imaging. So there's a new form of medicines and
Speaker 2: therapies where you make little fat droplets and you can
Speaker 2: decorate them with all kinds of molecules that either home
Speaker 2: to different parts of your body, and you can see
Speaker 2: them on X ray. You can put drugs inside, you
Speaker 2: can do all kinds of things with them.
Speaker 1: Well, just to be clear, these fat droplets, as you're
Speaker 1: describing them, like, they were the technology used to encapsulate
Speaker 1: the COVID vaccines, right, that's RNA covid vaccines were in
Speaker 1: what lipid NAO particle is? That is the jargon, right,
Speaker 1: although I like exactly I appreciate that.
Speaker 2: Yeah, so yeah, liposomas was used for or a fat
Speaker 2: droplet was used for the covid vaccine, and it's used
Speaker 2: for other things too. So what doctor pan Depongen Pans
Speaker 2: a brilliant chemical engineer. So he was making particles so
Speaker 2: that you could see specific things. So you want to
Speaker 2: be able to see breast cancer, You want to be
Speaker 2: able to see a blood clot. You want to see,
Speaker 2: you know, a particular type of cell. Then you put
Speaker 2: something on a fat droplet that finds that cell, and
Speaker 2: you put a little metal in the droplet that you
Speaker 2: can see with a special CT scan and then say
Speaker 2: suddenly I see very small and tiny, hard to detect
Speaker 2: cancers and so on. So he was making these particles,
Speaker 2: and he was doing them in a way he wanted
Speaker 2: to make a lot of surface area, and he ended
Speaker 2: up making particle that looked like red blood.
Speaker 1: Cells just by happenstance. He just looked at it one
Speaker 1: and said, hey, I know what that looks like a
Speaker 1: red blood cell.
Speaker 2: So red blood cells are also trying to have a
Speaker 2: lot of surface area because they exchange gas, and he
Speaker 2: was trying to create a lot of surface area for
Speaker 2: a different reason, so he could decorate the particles with
Speaker 2: these proteins, and then you get.
Speaker 1: Red blood cells, said trying to think of what they
Speaker 1: look like, and I thought of bali, which is kind
Speaker 1: of a niche a niche analogy, right, like a bagel,
Speaker 1: but with a thin doe part in where the hole
Speaker 1: would be. Do you have a go to description of
Speaker 1: a red blood cell? That's what we used.
Speaker 2: They're called Nanobiali's no kidding, yes, or the other word
Speaker 2: people say a biconcave disc Yeah.
Speaker 1: That's less or less? Uh that's cool? Yes, okay, So
Speaker 1: does he come to you with this, right, So what
Speaker 1: happens He's like, Oh, that looks like a red blood cell.
Speaker 1: What does he do?
Speaker 2: So he thought, Hey, I want wonder if I could
Speaker 2: put hemoglobin inside. And he was loosely familiar with the
Speaker 2: problems with auction carriers and he says, I wonder if
Speaker 2: I could just put hemoglobin inside, and he figured out
Speaker 2: how to do that, and then he's like, I don't
Speaker 2: know how to tell if this works or not. So so
Speaker 2: we're both at wash YOU and wash You has this
Speaker 2: collaboration website where you can google or it's.
Speaker 1: Like googling, but it's just at WashU the university. Interesting
Speaker 1: like an internal like an engine.
Speaker 2: Yeah, so he searched red blood cell physiology and I
Speaker 2: popped up. And so he called me and told me
Speaker 2: the story and said, you know, why don't you come
Speaker 2: over to my lab and and I'd like to show
Speaker 2: you what we're doing and see if this works, and maybe.
Speaker 1: We could figure out how to collaborate. Well it didn't work, huh,
Speaker 1: But but wait, what do you mean it didn't work?
Speaker 1: I was all ready for a to work.
Speaker 2: What didn't Well, it's a little more to it than
Speaker 2: just putting hemoglobein inside a fat droplet. So what I
Speaker 2: realized is conceptually this would solve the problem that the
Speaker 2: unencapsulated hemoglobins were plagued by this were like little red
Speaker 2: blood cells. And if we could figure out the chemistry
Speaker 2: to make this capture and release oxygen that maybe this
Speaker 2: would you know, make things safe and and you can
Speaker 2: freeze dry these things so they could be you know,
Speaker 2: shelf stable and very lightweight.
Speaker 1: So it's like instant coffee, but for red blood cells.
Speaker 1: That's the dream. Yeah, yeah, exactly. So initially it doesn't work,
Speaker 1: but you realize that the idea is fundamentally plausible. So
Speaker 1: like one of the things you have to sort of
Speaker 1: figure out make work for this.
Speaker 2: Torque a number of things from the inside out.
Speaker 1: OK.
Speaker 2: So, first of all, you've got a droplet that has
Speaker 2: hemoglobin inside it. Hemoglobin the reason red blood cells work.
Speaker 2: There are a lot more than just bags of hemoglobin.
Speaker 2: They have lots of other functions. And so we had
Speaker 2: to decide what are we going to keep and what
Speaker 2: do we get rid of?
Speaker 1: Huh, Because you can't build the whole red blood cell.
Speaker 1: We don't know how to do that. It's nice. You
Speaker 1: want to do as little as you can get away with.
Speaker 2: Right, right, You want the stripped down yeah, basic thing,
Speaker 2: and so it just has to transport oxygen and then
Speaker 2: it has to not do a bunch of other things.
Speaker 1: Yeah, we don't want it to cause trouble either. Well
Speaker 1: and subtly suddenly when you say transport oxygen. It has
Speaker 1: to know when to pick up oxygen from the lungs
Speaker 1: and has to know when to release oxygen to whatever
Speaker 1: tissue needs it. Right, Like that part seems hard from
Speaker 1: the outside, right, Well they're opposites. Yeah, yeah, and it
Speaker 1: has to do it at the right time, right, it
Speaker 1: has to do in the yes, at the right speed.
Speaker 2: So yeah, it's all very finely tuned inside our body.
Speaker 2: So we had to try to imitate the behavior of
Speaker 2: a real red cell, and the real red cell has
Speaker 2: people understand like, Okay, there are these other molecules inside
Speaker 2: red cells that modify the way the hemoglobin interacts with
Speaker 2: aucygen that causes it to capture oxygen effectively in the
Speaker 2: lung and then let go when it gets out in
Speaker 2: tissue and the red cells responding. Red cell doesn't know,
Speaker 2: oh I'm in the lung, Oh I'm in the lip,
Speaker 2: I'm in the muscle. So it's looking for cues. So
Speaker 2: it doesn't have a map, but it can almost smell
Speaker 2: where it is because of the chemicals that are different
Speaker 2: in the lung.
Speaker 1: Than in exercising muscle.
Speaker 2: And it's primarily responding to the amount of acid and
Speaker 2: the amount of carbon oxide that's in the blood. And
Speaker 2: so what we did is we created responsive elements that
Speaker 2: would work like red cells, but in a different way,
Speaker 2: so that they would change their shape or change their
Speaker 2: ability to interact with other molecules in response to those
Speaker 2: two signals carbon dioxide and acid. So then the artificial
Speaker 2: red cell quote knows it's in the lung or knows
Speaker 2: it's in the muscle. So we call that wetwear. So
Speaker 2: it's like a thousand little thermostats inside each little particle,
Speaker 2: and it's telling the hemoglobin what to do.
Speaker 1: I'm sure there are a lot of hard parts, but
Speaker 1: that sounds like the hard part.
Speaker 2: Well that was, Yeah, that was one of the hard right.
Speaker 2: Then we have to make it silent to the immune
Speaker 2: system so our body doesn't recognize it. We have to
Speaker 2: make sure that it doesn't alter the viscosity of blood
Speaker 2: so it doesn't get too thick or too thin, and
Speaker 2: then we have to make sure it doesn't interact with
Speaker 2: the blood clotting system, it doesn't cause blood clots or
Speaker 2: interfere with blood clots. And then we have to make
Speaker 2: it freeze dry, and then you know, we have to
Speaker 2: make it circulate for a long time. We have to
Speaker 2: evade the body system for clearing things that shouldn't be
Speaker 2: in our blood out of our blood.
Speaker 1: And so once we solve all those.
Speaker 2: Things, you know, then you know now it's working in
Speaker 2: an animal model. And that's why the very first one
Speaker 2: didn't work because while doctor Pan had already figured out
Speaker 2: how to get hemoglobin inside the fat droplet, it didn't
Speaker 2: do any of these other things yet.
Speaker 1: So is there a moment when you decide, oh, we
Speaker 1: should start a company.
Speaker 2: Yes, and so we started the company when we had
Speaker 2: first demonstrated proof of concept that we could create art
Speaker 2: official red cell. At that point we have a different task.
Speaker 2: So the original academic task was can we design an
Speaker 2: artificial cell? Can we prove that it works. Once we've
Speaker 2: done that, we now have a development commercial development task,
Speaker 2: which is can we make it reliably? Can we make
Speaker 2: it over and over again? Can we make a lot
Speaker 2: of it? Can we make sure that it passes all
Speaker 2: the safety and efficacy criteria FDA.
Speaker 1: So that task we need a company for.
Speaker 2: It's very different than a university task, and that's when
Speaker 2: we formed Kalasite in.
Speaker 1: Order to do those things. We'll be back in just
Speaker 1: a minute. Right that in twenty twenty three, you've got
Speaker 1: a forty six million dollars DARPA grant we're part of that.
Speaker 1: Tell me about that. That seems like a big moment
Speaker 1: in the history of this project. That was the moment. Yeah,
Speaker 1: So we had been working on in a reasonably successful
Speaker 1: way developing the red blood cells, artificial red cells.
Speaker 2: But what DARPA wanted. DARPA wanted everything. They wanted all
Speaker 2: the function of blood, so the ability to clot. So
Speaker 2: for a soldier, i'd basically, if you need artificial red cells.
Speaker 1: It's because you're bleeding.
Speaker 2: By definition, If you just replace the red cells and
Speaker 2: you don't replace the clotting factor, then it's like pouring
Speaker 2: blood into a sieve. It just falls back out again.
Speaker 2: It's ineffective. So they realize that we need to be
Speaker 2: able to replace everything, and to do that at the
Speaker 2: point of injury, you need freeze tride plasma, you need
Speaker 2: freeze stride platelets, you need free stride red cells, and
Speaker 2: it has to be scalable, and you know, there are
Speaker 2: a lot of logistic concerns. So what they put out
Speaker 2: a call for applications for teams to form from the
Speaker 2: people who are working on each of those components, and
Speaker 2: everybody had just been working on them separately to come
Speaker 2: together and form a consortium that would figure out how
Speaker 2: to make all these different components compatible and equivalent.
Speaker 1: To stored blood. So we built a consortium to do
Speaker 1: that and we completed effectively to win that award. What
Speaker 1: is the status of the would you call it artificial
Speaker 1: whole blood? What do you call the whole package?
Speaker 2: Unfortunately, we don't have a very sexy name for it yet.
Speaker 2: We call it the whole blood analog. So you know,
Speaker 2: it's not completely artificial because it's a biologically derived PLASMI.
Speaker 2: It's just regular plasma that's been freeze stride. The platelets
Speaker 2: are fully synthetic, so they help, you know, form blood
Speaker 2: clots to stop the bleeding, to stop the bleeding, which
Speaker 2: is you know, that's why they're getting this material.
Speaker 1: And so we sort of have two threads going now, right,
Speaker 1: there's how is it going on your artificial red blood cells?
Speaker 1: And then how is the whole blood analog project going?
Speaker 1: So let's just take those in order, like, what is
Speaker 1: the status of the like, are you testing the artificial
Speaker 1: red blood cell on its own? In oh? Yes, in
Speaker 1: clinical trials. Is that part of the plan to do
Speaker 1: that by itself or do you does it need to
Speaker 1: be the whole package.
Speaker 2: Well, it has to be tested by itself first, and
Speaker 2: so as a standalone element. And so we are still
Speaker 2: in what's called pre clinical testing. So we're testing in
Speaker 2: animal models and in parallel we're developing the combined product
Speaker 2: which will be sequentially administered plasma two, carrier and platelet,
Speaker 2: and that's also in pre clinical testing.
Speaker 1: Two is the red blood cell is the red blood cell,
Speaker 1: that's right, and plasma and platelet and that is expected
Speaker 1: that will follow. So we have to first test each
Speaker 1: element by itself before we start mixing cocktails. That's so hard,
Speaker 1: Like I feel like the way fractional probabilities work. If
Speaker 1: a bunch of things have to work separately and there's
Speaker 1: some you know, the fractions multiply, right, so it gets
Speaker 1: less and less likely that'll work just probabilistically, right. But
Speaker 1: what we have the ability to do is adapt to
Speaker 1: what we find, and that's what we've had to do.
Speaker 1: So we took these components, and of course they didn't
Speaker 1: automatically work altogether, so we weren't able to just take
Speaker 1: the red blood cells and the plasma and the platelets
Speaker 1: and just put them in a blender and get blood.
Speaker 2: So we've had to tune. We're actually now on version
Speaker 2: four zero point one point two of the starting with
Speaker 2: version zero of the System of the.
Speaker 1: Whole Blood of the whole Blood analog. Yes, yeah, okay.
Speaker 1: And is it right that there are other groups? Is
Speaker 1: there a group in Japan working on something similar? Tell
Speaker 1: me about that, and tell me about the field more broadly,
Speaker 1: other similar projects. Sure.
Speaker 2: The other main encapsulated program is in Japan, led by
Speaker 2: a really successful scientists named Romi Sakai.
Speaker 1: He's been working on this for over a decade, developing
Speaker 1: another's It's.
Speaker 2: Essentially the same concept. It's a liposome with hemoglobin on
Speaker 2: the inside, a fat droplet, A fat droplet, Yeah right,
Speaker 2: it's a fat droplet, and it's a little different. It
Speaker 2: doesn't have that wetwear system that we talked about. He's
Speaker 2: adjusted the auction affinity to be sort of in the middle,
Speaker 2: so it's pretty good at capturing auction in the lung
Speaker 2: and pretty good at letting it go and tissue. It
Speaker 2: doesn't shift up and down depending on where it is,
Speaker 2: so it's good enough. It works and he's already begun
Speaker 2: to test its safety in humans. Now it's it's not
Speaker 2: freeze drive. It's still in water, and they are not
Speaker 2: working on combining it with plasma and platelets.
Speaker 1: It's just the two carrier. How do you think it's
Speaker 1: going that the Japanese version?
Speaker 2: Great, They're they're out in front, so they've they've tested
Speaker 2: in humans and they had some minor issues that I
Speaker 2: think have been probably been addressed in and it's incredibly exciting.
Speaker 2: We're all benefiting from doctor Sakai's leadership.
Speaker 1: So to return to your own work and the work
Speaker 1: of the consortium that you're part of, what's the happy story?
Speaker 1: Like how long in the future do you think about
Speaker 1: and what do you think about when you think about
Speaker 1: it going well? Uh So, if you think about it
Speaker 1: going well, I guess there's a presumption baked into that question.
Speaker 1: Mostly I think about, you know, how it's not going
Speaker 1: to go well? Okay, Well, how might it not go well?
Speaker 1: I mean I guess that one's easier to imagine in
Speaker 1: some ways, but how might it not go well?
Speaker 2: I Mean, what I'm really worried about is the things
Speaker 2: I can't imagine, So the things we imagine we're constantly
Speaker 2: trying to think.
Speaker 1: Of how it won't go well, and we try.
Speaker 2: To anticipate a solution to the problem and fix it.
Speaker 2: The things that we can't plan for, of course, are
Speaker 2: the things that we don't yet understand.
Speaker 1: The drums felled in unknowns. Yeah you beat me to it.
Speaker 2: Yeah yeah, so and that happens monthly, where it's like, uh, oh,
Speaker 2: we didn't think of that. Now we have to solve
Speaker 2: a new problem because we're off the map, you know,
Speaker 2: we don't really nobody's been.
Speaker 1: Here before, so we have to figure those things out.
Speaker 1: Does it seem impossibly hard? Like, frankly, this one, this
Speaker 1: project just seems so hard, right, It is hard. If
Speaker 1: it were easy, it'd be done already.
Speaker 2: But the wonderful thing is that I think that we
Speaker 2: have all the tools that we need to solve the problem.
Speaker 2: So the advances in synthetic chemistry are impossible to overstate.
Speaker 2: The advances in nanomedicine and nanofabrication are allowing us to
Speaker 2: respond in very quick ways. The ability to use machine
Speaker 2: learning and artificial intelligence to improve our design is reducing
Speaker 2: the need to do thousands and thousands of experiments, so
Speaker 2: we can use the computers to tell us the likely
Speaker 2: things to work, and it reduces the empiric burden. And
Speaker 2: we've got great resources because the NIH and Department of
Speaker 2: Defense DARPA put a lot of resources in our hands.
Speaker 2: So we're very fortunate that we can very quickly respond
Speaker 2: to the problems that we encounter. So it works very
Speaker 2: effectively in the models that we have. But now we
Speaker 2: also have to make this scale. So that's another huge challenge.
Speaker 2: So we have to go from making what you might
Speaker 2: call craft beer to Budweiser.
Speaker 1: And just to be clear, it's made from real blood, right,
Speaker 1: Like the humoglobin in your lipid nanoparticles is hemoglobin from people, right,
Speaker 1: It's not synthesized. So that is a scale challenge right there, Right,
Speaker 1: that's impossible.
Speaker 2: Right, So we can't synthesize hemoglobin from amino acids. That
Speaker 2: is beyond our current capability, but we can program other
Speaker 2: organisms to make it for.
Speaker 1: Us, like yeast. Ideally yeast right put it in a
Speaker 1: fact is that the yeah, we're going to brew it.
Speaker 2: So we have a Yeast project where we are training
Speaker 2: yeast to make human hemoglobin and to secrete it, and
Speaker 2: that will eventually be our source.
Speaker 1: So okay, So take thirty seconds off of thinking about
Speaker 1: all the things that can go wrong and that you
Speaker 1: have to figure out, and just tell me if some
Speaker 1: you or the people who come after you even respectfully
Speaker 1: figure out how to do all the things you're trying
Speaker 1: to do, what will it look like? What will it
Speaker 1: look like? Right?
Speaker 2: Well, we actually believe it or not have done that.
Speaker 2: We have a prototype of the delivery system. We've been
Speaker 2: simultaneously trying to work with the people who would be
Speaker 2: using it so that we don't end up with an
Speaker 2: end product. And they say, but did you think about X?
Speaker 2: And we just like, uh, So.
Speaker 1: A person gets in a car accident or a soldier
Speaker 1: gets shot on the battlefield, what happens in this future
Speaker 1: where the thing you're working on works.
Speaker 2: So what they'll have is a kit, and in the
Speaker 2: kit will be three components, the two carrier, the plasma,
Speaker 2: and the platelet. All of them will be dry powders. Okay,
Speaker 2: So the instructions that we got from the Department of
Speaker 2: Defense were it has to work in the dark, in
Speaker 2: a ditch, under fire, and it has to be usable
Speaker 2: by somebody who has basically known medical training. So that's
Speaker 2: basically you know, not a sophisticated nurse or a scientist.
Speaker 1: Basically, they want you to make instant coffee, but for blood.
Speaker 2: But for blood, but also it's instant coffee. It's too complicated.
Speaker 2: You've got to heat the water, you've got to dispense
Speaker 2: it from a jar into a cup.
Speaker 1: And pour the water. You can't do any of that.
Speaker 2: So what we have is a system that has a
Speaker 2: split bag with a dry side and a wet side
Speaker 2: and something called a weak weld. So when it's folded over,
Speaker 2: you can stand on it and it won't open. But
Speaker 2: when you unfold it, you squeeze it and it pops
Speaker 2: and the water migrates from one side to the other
Speaker 2: and hydrates the dry material, and then it slashes around
Speaker 2: in there for about a minute, and then you hang
Speaker 2: it and you can use it just like a unit
Speaker 2: of blood.
Speaker 1: Right, you hang it like a like a ba that
Speaker 1: goes into your arm on an.
Speaker 2: Iterate, And there's one like that for the plasma and
Speaker 2: the platelet's a little different because it's a much smaller volume.
Speaker 2: That eventually will be what's called an autoinjector. Everybody's seen EpiPens,
Speaker 2: so it'll be like an EpiPen. Now there's an additional problem.
Speaker 2: Damn yes, there's two other problems really. So one is
Speaker 2: for it to be shelf stable, it can't interact with
Speaker 2: oxygen in the air. So water and iron and oxygen
Speaker 2: equals rust.
Speaker 1: Yeah, when you think about hemoglobin, it seems like rust, right, hemoglobin.
Speaker 1: It's iron in the hemoglobin that is binding to the oxygen. Right,
Speaker 1: And I'm like, wait, is hemoglobin just rusting all the time?
Speaker 1: In my blood? Is going?
Speaker 2: In fact, right now your hemoglobin is rusting about ten
Speaker 2: percent of it is rusting constantly. But you have a
Speaker 2: rust remover inside your red blood cells. That is, every
Speaker 2: time it goes around, there's a little molecule in there
Speaker 2: that's scrubbing the rust and demolishing the polishing the iron.
Speaker 2: So we have to we have to prevent that from
Speaker 2: happening during storage. And to do that, we have to
Speaker 2: have a plastic soft plastic, but that has glass like properties,
Speaker 2: so it doesn't allow water or oxygen through it.
Speaker 1: And so that's a very.
Speaker 2: Novel film that we are applying for the first time
Speaker 2: to blood storage. The other problem is it can't be cold.
Speaker 2: So I don't know if you've ever tried to hydrate
Speaker 2: freez strike coffee with tapwater, it just makes clumps. It
Speaker 2: doesn't it doesn't hydrate, so we actually have to warm it.
Speaker 1: So we have to.
Speaker 2: Build a heater into the bag system. So this is
Speaker 2: another layer of plastic that has a little circuit inside,
Speaker 2: and the circuit, when you turn it on, it will
Speaker 2: warm the liquid and then it will turn color and
Speaker 2: then the medic will know, okay, I can squeeze it.
Speaker 2: And all the medic has to do is tear it open,
Speaker 2: unfold the bag, wait for it to change color, squeeze it,
Speaker 2: slash it a bit, and then hang it.
Speaker 1: And that's the way it will work. That's the user
Speaker 1: manual version of how it will work. What's the like
Speaker 1: thirty thousand foot version of like just at a macro level,
Speaker 1: somebody who didn't know what was going on, Like what
Speaker 1: would they see and how would the world be different
Speaker 1: if this works?
Speaker 2: Well, first of all, every soldier would carry this in
Speaker 2: their cargo pants, so they would have their own blood
Speaker 2: instead of a blood tag that like now it just
Speaker 2: says i'm typo, I'm type whatever. They actually have what
Speaker 2: they need in their pants, so if they go down,
Speaker 2: a medic can come up, take it out, and you know,
Speaker 2: put it, you know, start resustinating somebody. It will be
Speaker 2: in every ambulance so that if somebody goes to the
Speaker 2: scene of an accident somebody's bleeding, they'll be able to
Speaker 2: give them blood right away, just like they can of
Speaker 2: oxygen or CPR. It will be stored in depots for
Speaker 2: mass casualty incidents. So many people don't know at the say,
Speaker 2: for example, at the Boston Marathon bombing, they actually were
Speaker 2: running out of blood there, and unfortunately those incidents haven't stopped.
Speaker 2: So there will be depots around the country where there's
Speaker 2: warehouse shell stable blood. It will be on cruise ships.
Speaker 2: It will be in resource limited countries like sub Saharan Africa.
Speaker 2: It will be on the space station. It will be
Speaker 2: on the mission to Mars. It will be wherever it's
Speaker 2: hard to get blood. We'll be back in a minute
Speaker 2: with the lightning round.
Speaker 1: Okay, lightning round. What's your second favorite type of blood cell?
Speaker 1: Nice as opposed to red blood I'm assuming I'm presuming
Speaker 1: that red blood cells are your favorite, right, Yeah, the
Speaker 1: juvenile red blood cells, the red cell, the cells that
Speaker 1: make red blood cells. Okay, third favorite, third favorite? Yeah, sorry,
Speaker 1: well i'd say platelets are pretty important and they're far
Speaker 1: more complicated than red blood cells. But no platelets and
Speaker 1: we just bleed to death. So plate is very important
Speaker 1: and fascinating the whole. Like clotting cascade things seems wild,
Speaker 1: right because you want the blood to clot when it
Speaker 1: needs to clot, but you really don't want it to
Speaker 1: clot when it's not supposed to clot, right, Like, that's
Speaker 1: such a high stakes equilibrium.
Speaker 2: It's an amazing system and amazing that it works when
Speaker 2: it does. But yes, clotting system is incredible and very
Speaker 2: very complicated.
Speaker 1: What's one thing you wish we understood about blood that
Speaker 1: is still a mystery why we have to keep remaking it?
Speaker 2: So the you know, we have to renew red blood
Speaker 2: cells every three months. They don't last very long. We
Speaker 2: live with the neurons that we started with as a baby,
Speaker 2: but the red cells you had in the spring, they're
Speaker 2: all gone, Every last one of them is gone. So
Speaker 2: you turn over all of your red blood cells. And
Speaker 2: it's incredible that we actually do that because it's a
Speaker 2: huge part of our quote budget in terms of energy
Speaker 2: and nutrition.
Speaker 1: It would be a huge evolutionary advantage in a world
Speaker 1: of scarce food, presumably, so there must be some reason
Speaker 1: that it doesn't work, right, Yeah, but we don't know.
Speaker 1: What's one common misconception that lay people have about blood
Speaker 1: that it's not alive. It's as alive as your brain.
Speaker 1: People forget your blood is a living tissue.
Speaker 2: Is just a liquid organ, and it's alive, and it's
Speaker 2: constantly doing things.
Speaker 1: It's very very sensitive.
Speaker 2: It responds perfectly to you know, when you need to
Speaker 2: increase oxygen delivery or reduce it. It can clot, it
Speaker 2: can fight infection. It has a lot of functions. And
Speaker 2: people just think, well, it's just you know, like motor oil.
Speaker 2: But it's it's very sophisticated.
Speaker 1: What's your view on nominative determinism? Nominative determinatism? So are
Speaker 1: we what we call ourselves? Is that? Yes, I'm frankly
Speaker 1: surprised that you have not heard that phrase. I'll be
Speaker 1: honest with you. Yeah.
Speaker 2: So my last name, so, I fought it for a
Speaker 2: long time. In fact, wanted to become a marine biologist.
Speaker 1: I Jacques Cousteau was my idol when I was growing up,
Speaker 1: and but you know, I succumbed and went to medical school.
Speaker 1: I'm actually quite happy that I did. Doctor Alan Doctor
Speaker 1: is a professor of pediatrics and bioengineering at the University
Speaker 1: of Maryland and he's the co founder and chief scientific
Speaker 1: officer of Kalosite. Please email us at problem at pushkin
Speaker 1: dot fm. We are always looking for new guests for
Speaker 1: the show. Today's show was produced by Trinomanino and Gabriel
Speaker 1: Hunter Chang. It was edited by Alexander Garretson and engineered
Speaker 1: by Sarah Brugueir. I'm Jacob Goldstein and we'll be back
Speaker 1: next week with another episode of What's Your Problem.