WEBVTT - Reinventing Blood 0:00:15.356 --> 0:00:23.636 Pushkin. Every year, sixty thousand people in the United States 0:00:23.916 --> 0:00:27.516 and two million people around the world die because of 0:00:27.596 --> 0:00:31.036 blood loss. They get in a car accident, or they 0:00:31.036 --> 0:00:35.436 get shot and they bleed to death. These people tend 0:00:35.436 --> 0:00:38.556 to be relatively young and healthy, and a lot of 0:00:38.596 --> 0:00:41.316 them could be saved if they were quickly given blood. 0:00:41.716 --> 0:00:45.796 But outside the body, blood doesn't travel well. It's bulky. 0:00:46.076 --> 0:00:48.556 You have to keep it cold, and as a result, 0:00:48.716 --> 0:00:52.036 it's hard to get blood to patience when they urgently 0:00:52.196 --> 0:00:56.636 need it. Ambulances don't tend to carry it. Field medics 0:00:56.636 --> 0:00:59.916 don't typically have it in combat, and so there's long 0:00:59.956 --> 0:01:02.916 been this dream. What if we could come up with 0:01:02.956 --> 0:01:06.636 a way to make blood easier to store and transport. 0:01:07.396 --> 0:01:09.756 What if we could have blood ready to go every 0:01:09.836 --> 0:01:12.436 time an ambulance gets to a car accident and a 0:01:12.476 --> 0:01:15.516 medic gets to a wounded soldier. If we could do that, 0:01:16.036 --> 0:01:25.996 we could save millions of lives. I'm Jacob Goldstein and 0:01:25.996 --> 0:01:27.796 this is What's Your Problem, the show where I talk 0:01:27.836 --> 0:01:31.036 to people who are trying to make technological progress. My 0:01:31.116 --> 0:01:34.396 guest today is Alan Doctor. He's the co founder and 0:01:34.476 --> 0:01:39.396 chief scientific officer at Kalasite. Alan's problem is this, can 0:01:39.436 --> 0:01:43.276 you make something like freeze dried blood that can be 0:01:43.516 --> 0:01:46.836 rehydrated and given to patients when and where they need it. 0:01:47.916 --> 0:01:50.756 Alan didn't start out wanting to found a company. He 0:01:50.836 --> 0:01:53.076 was a doctor taking care of kids in the hospital. 0:01:53.556 --> 0:01:55.956 So the type of medicine I do is intensive care 0:01:55.996 --> 0:02:00.036 of medicine. So this is and for children, looking after 0:02:00.436 --> 0:02:04.556 children in the hospital who have severe infections or major 0:02:04.636 --> 0:02:08.956 injuries and they're critically ill, and most of them are 0:02:08.956 --> 0:02:12.436 in something a condition we call shock. And the problem 0:02:12.556 --> 0:02:17.396 with shock is that you're not effectively getting blood and 0:02:17.556 --> 0:02:22.436 oxygen where it's needed. Okay, so people get sick and die. 0:02:22.876 --> 0:02:25.836 Even though we fix the underlying problem, so we can 0:02:25.916 --> 0:02:29.556 cure the infection, we repair the hole in the blood vessel, 0:02:30.116 --> 0:02:34.836 and people still we lose them because their circulatory system 0:02:34.876 --> 0:02:35.476 is failing. 0:02:35.836 --> 0:02:35.996 You know. 0:02:36.076 --> 0:02:38.716 That was frustrating, and I was interested in that problem 0:02:38.836 --> 0:02:41.196 and I was trying to understand why that happened. And 0:02:41.356 --> 0:02:45.716 what we were able to learn is there's a traffic 0:02:45.796 --> 0:02:50.716 control system in our circulatory system that routes blood where 0:02:50.716 --> 0:02:54.596 it needs to go, and red blood cells are the 0:02:54.636 --> 0:02:59.316 traffic lights, so they turn green and they open up 0:02:59.316 --> 0:03:01.836 the blood vessels or they turn red and close them, 0:03:01.996 --> 0:03:06.996 and it's very coordinated. It's a very exquisitely tuned system. 0:03:07.156 --> 0:03:11.756 And I was studying that, huh, that's governed by the 0:03:11.796 --> 0:03:16.756 way hemoglobin interacts with other chemicals in our blood stream. 0:03:17.076 --> 0:03:20.756 And it turns out it's highly relevant for shock and 0:03:20.836 --> 0:03:24.956 fixing shock. But it turns out it's also relevant for transfusion. 0:03:25.356 --> 0:03:27.476 And that's when this story started. 0:03:27.916 --> 0:03:31.316 So you're studying red blood cells and hemoglobin, which are 0:03:31.356 --> 0:03:35.876 obviously hemoglobin are the molecules that transport oxygen, right, that 0:03:35.956 --> 0:03:39.996 do that key function of blood. That is the thing 0:03:40.236 --> 0:03:43.356 in particular that you want to replace when somebody gets 0:03:43.356 --> 0:03:45.316 shot or gets in a car accident. Right, of all 0:03:45.356 --> 0:03:47.396 the things in your blood, the thing you need urgently 0:03:47.476 --> 0:03:51.756 that minute is hemoglobin to deliver the oxygen right. Right. 0:03:51.796 --> 0:03:53.756 People had known that part for a long time and 0:03:53.836 --> 0:03:58.476 had tried to develop blood substitutes in particular to solve 0:03:58.476 --> 0:04:01.756 this acute kind of trauma setting problem. But it had 0:04:01.796 --> 0:04:05.836 gone badly right, So tell me about the history up 0:04:05.916 --> 0:04:09.036 until that point of people trying to come up with 0:04:09.236 --> 0:04:12.636 ways to you know, get hemoglobin to people in emergencies, 0:04:12.676 --> 0:04:14.396 do sort of hemoglobin replacements. 0:04:15.036 --> 0:04:18.596 Well, they did the first obvious thing. So the problem 0:04:18.716 --> 0:04:21.596 is you have to make the bloodshelf stable in order 0:04:21.676 --> 0:04:25.876 to use it outside of hospitals, So you have to 0:04:25.876 --> 0:04:29.036 get rid of the cold chain. The reason we need 0:04:29.076 --> 0:04:32.876 the cold chain is the hemoglobin's inside a red blood cell. 0:04:32.956 --> 0:04:37.116 The red blood cell's alive, and it needs glucose, it 0:04:37.156 --> 0:04:40.076 needs all kinds of things, and it has to be 0:04:40.196 --> 0:04:43.356 kept colder. It goes bad, sort of like the way 0:04:43.396 --> 0:04:46.556 milk has to be kept colder. It goes bad, and 0:04:46.716 --> 0:04:49.116 you can't leave it outside the fridge too long or 0:04:49.276 --> 0:04:50.436 you can't drink it. 0:04:50.556 --> 0:04:51.676 The same thing with blood. 0:04:52.836 --> 0:04:55.156 So they say, okay, if we just take the hemoglobin 0:04:55.196 --> 0:04:58.196 out of the red cell, will it still capture and 0:04:58.236 --> 0:04:59.116 release oxygen? 0:04:59.356 --> 0:05:02.836 Yes, okay it will. So far, so good, So far, 0:05:02.916 --> 0:05:03.316 so good. 0:05:03.676 --> 0:05:08.236 Does it need to be kept cold in order to work, No, 0:05:08.596 --> 0:05:13.116 it doesn't, So it's shelf stable. Doesn't work if we 0:05:13.156 --> 0:05:18.276 put it inside animals. Pretty much it does, and so 0:05:18.636 --> 0:05:20.516 everybody's like, okay, let's try this. 0:05:20.636 --> 0:05:20.836 Yeah. 0:05:21.596 --> 0:05:25.276 And it was a catastrophe, so it wasn't just ineffective. 0:05:25.316 --> 0:05:29.316 It was harmful, so it was more harmful than the controls. 0:05:29.396 --> 0:05:32.956 So it caused heart attacks and strokes and death in 0:05:33.036 --> 0:05:34.516 the people that got the blood. 0:05:34.636 --> 0:05:37.236 Why is it bad to give people hemoglobin? That is 0:05:37.276 --> 0:05:42.076 a surprising outcome, right, It's not like it's some novel molecule. 0:05:42.156 --> 0:05:44.876 It's our bodies are full of hemoglobin, all right. 0:05:44.956 --> 0:05:47.956 So what it meant was we didn't understand something. It 0:05:47.996 --> 0:05:52.916 turns out hemoglobin does more than just interact with oxygen. 0:05:52.996 --> 0:05:56.436 It interacts with other chemicals in the blood stream. So 0:05:57.156 --> 0:06:00.836 the hemoglobin has to be sheathed inside a membrane, and 0:06:00.916 --> 0:06:05.236 it sequesters the hemoglobin from everything else in the blood stream, 0:06:05.716 --> 0:06:08.796 from the blood vessels, the cells that line the blood vessel, 0:06:08.836 --> 0:06:13.556 from the chemicals in the bloodstream where it won't do 0:06:13.716 --> 0:06:16.996 things it's not supposed to do. And it turns out 0:06:17.276 --> 0:06:20.476 that when hemoglobin is free in the bloodstream, the blood 0:06:20.556 --> 0:06:23.036 vessels don't know whether they're to open or close, and 0:06:23.116 --> 0:06:25.396 what they end up doing is mostly closing. 0:06:25.596 --> 0:06:29.196 Uh huh. So that's why people who got just naked 0:06:29.236 --> 0:06:33.356 hemoglobin had heart attacks. Basically exactly, yeah, exactly, got it. 0:06:33.476 --> 0:06:36.916 So okay, So this is the context, right, So clear 0:06:37.716 --> 0:06:41.716 bad idea to just give people hemoglobin. Alas well, it 0:06:41.756 --> 0:06:43.836 was a good idea. It seemed like a good idea, 0:06:43.836 --> 0:06:45.796 but it became clear that it had been a bad idea. 0:06:45.836 --> 0:06:48.476 It's scary in fact, right, it scary like so many 0:06:48.596 --> 0:06:51.716 things we've all done. Yeah, yeah, no, no, no shade 0:06:51.756 --> 0:06:54.116 on the people who tried it. It's just a it's 0:06:54.156 --> 0:06:58.196 a terrible outcome that nobody would have wanted. So you meanwhile, 0:06:58.276 --> 0:07:04.156 are studying hemoglobin and then a chemical engineer comes to 0:07:04.196 --> 0:07:07.036 you with an idea, Right, tell me about that. Twenty 0:07:07.196 --> 0:07:07.876 ten what happened? 0:07:07.956 --> 0:07:11.756 Yeah, I'm just studying regular red blood cells and this 0:07:12.076 --> 0:07:16.596 routing problem, right, which I understood. That's why you know 0:07:16.876 --> 0:07:19.236 a lot of these blood substitutes, what we call the 0:07:19.356 --> 0:07:23.996 unencapsulated hemoglobins failed. People started to understand that, but I 0:07:24.076 --> 0:07:26.516 wasn't thinking like, oh, I know how to solve that problem. 0:07:26.916 --> 0:07:30.476 I was minding my own business doing something completely different. 0:07:30.756 --> 0:07:37.316 The chemical engineer, the bioengineer was making special particles, nanoparticles 0:07:37.356 --> 0:07:42.596 for imaging. So there's a new form of medicines and 0:07:42.676 --> 0:07:47.276 therapies where you make little fat droplets and you can 0:07:47.356 --> 0:07:52.116 decorate them with all kinds of molecules that either home 0:07:52.196 --> 0:07:54.236 to different parts of your body, and you can see 0:07:54.276 --> 0:07:56.756 them on X ray. You can put drugs inside, you 0:07:56.796 --> 0:07:58.316 can do all kinds of things with them. 0:07:58.636 --> 0:08:00.956 Well, just to be clear, these fat droplets, as you're 0:08:00.956 --> 0:08:05.116 describing them, like, they were the technology used to encapsulate 0:08:05.236 --> 0:08:10.196 the COVID vaccines, right, that's RNA covid vaccines were in 0:08:10.396 --> 0:08:12.796 what lipid NAO particle is? That is the jargon, right, 0:08:12.836 --> 0:08:14.796 although I like exactly I appreciate that. 0:08:14.876 --> 0:08:18.476 Yeah, so yeah, liposomas was used for or a fat 0:08:18.556 --> 0:08:21.956 droplet was used for the covid vaccine, and it's used 0:08:21.956 --> 0:08:26.716 for other things too. So what doctor pan Depongen Pans 0:08:26.796 --> 0:08:32.956 a brilliant chemical engineer. So he was making particles so 0:08:32.996 --> 0:08:36.076 that you could see specific things. So you want to 0:08:36.116 --> 0:08:38.156 be able to see breast cancer, You want to be 0:08:38.156 --> 0:08:41.116 able to see a blood clot. You want to see, 0:08:41.276 --> 0:08:43.916 you know, a particular type of cell. Then you put 0:08:43.956 --> 0:08:47.516 something on a fat droplet that finds that cell, and 0:08:47.556 --> 0:08:50.836 you put a little metal in the droplet that you 0:08:50.876 --> 0:08:55.156 can see with a special CT scan and then say 0:08:55.236 --> 0:08:58.996 suddenly I see very small and tiny, hard to detect 0:08:59.396 --> 0:09:02.836 cancers and so on. So he was making these particles, 0:09:03.356 --> 0:09:05.516 and he was doing them in a way he wanted 0:09:05.556 --> 0:09:08.316 to make a lot of surface area, and he ended 0:09:08.396 --> 0:09:11.476 up making particle that looked like red blood. 0:09:11.196 --> 0:09:14.796 Cells just by happenstance. He just looked at it one 0:09:14.836 --> 0:09:17.276 and said, hey, I know what that looks like a 0:09:17.316 --> 0:09:18.076 red blood cell. 0:09:18.196 --> 0:09:21.156 So red blood cells are also trying to have a 0:09:21.156 --> 0:09:24.636 lot of surface area because they exchange gas, and he 0:09:24.756 --> 0:09:26.836 was trying to create a lot of surface area for 0:09:26.876 --> 0:09:30.116 a different reason, so he could decorate the particles with 0:09:30.196 --> 0:09:32.676 these proteins, and then you get. 0:09:32.556 --> 0:09:34.396 Red blood cells, said trying to think of what they 0:09:34.436 --> 0:09:36.876 look like, and I thought of bali, which is kind 0:09:36.916 --> 0:09:41.236 of a niche a niche analogy, right, like a bagel, 0:09:41.236 --> 0:09:43.596 but with a thin doe part in where the hole 0:09:43.636 --> 0:09:45.676 would be. Do you have a go to description of 0:09:45.716 --> 0:09:47.716 a red blood cell? That's what we used. 0:09:47.756 --> 0:09:52.596 They're called Nanobiali's no kidding, yes, or the other word 0:09:52.636 --> 0:09:55.316 people say a biconcave disc Yeah. 0:09:55.196 --> 0:09:59.756 That's less or less? Uh that's cool? Yes, okay, So 0:09:59.836 --> 0:10:02.716 does he come to you with this, right, So what 0:10:03.036 --> 0:10:05.556 happens He's like, Oh, that looks like a red blood cell. 0:10:05.596 --> 0:10:06.156 What does he do? 0:10:06.836 --> 0:10:09.756 So he thought, Hey, I want wonder if I could 0:10:09.756 --> 0:10:14.596 put hemoglobin inside. And he was loosely familiar with the 0:10:14.716 --> 0:10:18.916 problems with auction carriers and he says, I wonder if 0:10:18.916 --> 0:10:22.716 I could just put hemoglobin inside, and he figured out 0:10:22.756 --> 0:10:25.756 how to do that, and then he's like, I don't 0:10:25.796 --> 0:10:29.116 know how to tell if this works or not. So so 0:10:28.836 --> 0:10:31.236 we're both at wash YOU and wash You has this 0:10:31.356 --> 0:10:34.676 collaboration website where you can google or it's. 0:10:34.476 --> 0:10:38.196 Like googling, but it's just at WashU the university. Interesting 0:10:38.316 --> 0:10:40.636 like an internal like an engine. 0:10:40.996 --> 0:10:46.276 Yeah, so he searched red blood cell physiology and I 0:10:46.396 --> 0:10:49.396 popped up. And so he called me and told me 0:10:49.476 --> 0:10:52.516 the story and said, you know, why don't you come 0:10:52.516 --> 0:10:55.556 over to my lab and and I'd like to show 0:10:55.556 --> 0:10:58.876 you what we're doing and see if this works, and maybe. 0:10:58.636 --> 0:11:03.436 We could figure out how to collaborate. Well it didn't work, huh, 0:11:03.476 --> 0:11:05.796 But but wait, what do you mean it didn't work? 0:11:05.836 --> 0:11:07.036 I was all ready for a to work. 0:11:07.116 --> 0:11:11.316 What didn't Well, it's a little more to it than 0:11:11.356 --> 0:11:15.556 just putting hemoglobein inside a fat droplet. So what I 0:11:15.636 --> 0:11:21.036 realized is conceptually this would solve the problem that the 0:11:21.156 --> 0:11:26.356 unencapsulated hemoglobins were plagued by this were like little red 0:11:26.396 --> 0:11:29.636 blood cells. And if we could figure out the chemistry 0:11:29.676 --> 0:11:33.636 to make this capture and release oxygen that maybe this 0:11:33.676 --> 0:11:36.596 would you know, make things safe and and you can 0:11:36.676 --> 0:11:39.676 freeze dry these things so they could be you know, 0:11:40.276 --> 0:11:42.636 shelf stable and very lightweight. 0:11:42.996 --> 0:11:46.076 So it's like instant coffee, but for red blood cells. 0:11:46.276 --> 0:11:51.036 That's the dream. Yeah, yeah, exactly. So initially it doesn't work, 0:11:51.076 --> 0:11:56.476 but you realize that the idea is fundamentally plausible. So 0:11:56.676 --> 0:11:59.676 like one of the things you have to sort of 0:12:00.076 --> 0:12:01.916 figure out make work for this. 0:12:02.356 --> 0:12:07.196 Torque a number of things from the inside out. 0:12:07.556 --> 0:12:07.676 OK. 0:12:07.716 --> 0:12:11.636 So, first of all, you've got a droplet that has 0:12:11.676 --> 0:12:16.836 hemoglobin inside it. Hemoglobin the reason red blood cells work. 0:12:16.876 --> 0:12:19.916 There are a lot more than just bags of hemoglobin. 0:12:19.996 --> 0:12:24.396 They have lots of other functions. And so we had 0:12:24.476 --> 0:12:27.036 to decide what are we going to keep and what 0:12:27.076 --> 0:12:28.036 do we get rid of? 0:12:28.316 --> 0:12:30.916 Huh, Because you can't build the whole red blood cell. 0:12:30.956 --> 0:12:33.036 We don't know how to do that. It's nice. You 0:12:33.276 --> 0:12:35.636 want to do as little as you can get away with. 0:12:35.676 --> 0:12:40.716 Right, right, You want the stripped down yeah, basic thing, 0:12:40.836 --> 0:12:43.996 and so it just has to transport oxygen and then 0:12:44.076 --> 0:12:46.316 it has to not do a bunch of other things. 0:12:46.356 --> 0:12:49.316 Yeah, we don't want it to cause trouble either. Well 0:12:49.316 --> 0:12:52.556 and subtly suddenly when you say transport oxygen. It has 0:12:52.596 --> 0:12:55.676 to know when to pick up oxygen from the lungs 0:12:55.756 --> 0:12:58.036 and has to know when to release oxygen to whatever 0:12:58.076 --> 0:13:02.156 tissue needs it. Right, Like that part seems hard from 0:13:02.196 --> 0:13:06.596 the outside, right, Well they're opposites. Yeah, yeah, and it 0:13:06.596 --> 0:13:08.756 has to do it at the right time, right, it 0:13:08.756 --> 0:13:12.316 has to do in the yes, at the right speed. 0:13:12.796 --> 0:13:16.036 So yeah, it's all very finely tuned inside our body. 0:13:16.476 --> 0:13:19.076 So we had to try to imitate the behavior of 0:13:19.076 --> 0:13:23.916 a real red cell, and the real red cell has 0:13:24.276 --> 0:13:27.996 people understand like, Okay, there are these other molecules inside 0:13:28.076 --> 0:13:32.276 red cells that modify the way the hemoglobin interacts with 0:13:32.356 --> 0:13:37.636 aucygen that causes it to capture oxygen effectively in the 0:13:37.716 --> 0:13:40.276 lung and then let go when it gets out in 0:13:40.356 --> 0:13:44.236 tissue and the red cells responding. Red cell doesn't know, 0:13:44.316 --> 0:13:47.236 oh I'm in the lung, Oh I'm in the lip, 0:13:47.476 --> 0:13:54.156 I'm in the muscle. So it's looking for cues. So 0:13:55.076 --> 0:13:58.276 it doesn't have a map, but it can almost smell 0:13:58.356 --> 0:14:01.196 where it is because of the chemicals that are different 0:14:01.236 --> 0:14:02.076 in the lung. 0:14:02.236 --> 0:14:03.756 Than in exercising muscle. 0:14:04.796 --> 0:14:08.316 And it's primarily responding to the amount of acid and 0:14:08.356 --> 0:14:12.436 the amount of carbon oxide that's in the blood. And 0:14:12.476 --> 0:14:18.316 so what we did is we created responsive elements that 0:14:18.596 --> 0:14:22.236 would work like red cells, but in a different way, 0:14:22.556 --> 0:14:27.436 so that they would change their shape or change their 0:14:27.676 --> 0:14:31.756 ability to interact with other molecules in response to those 0:14:31.796 --> 0:14:37.236 two signals carbon dioxide and acid. So then the artificial 0:14:37.276 --> 0:14:40.756 red cell quote knows it's in the lung or knows 0:14:40.796 --> 0:14:44.236 it's in the muscle. So we call that wetwear. So 0:14:44.316 --> 0:14:50.596 it's like a thousand little thermostats inside each little particle, 0:14:51.076 --> 0:14:53.596 and it's telling the hemoglobin what to do. 0:14:53.956 --> 0:14:55.436 I'm sure there are a lot of hard parts, but 0:14:55.516 --> 0:14:56.796 that sounds like the hard part. 0:14:57.036 --> 0:14:59.996 Well that was, Yeah, that was one of the hard right. 0:15:00.076 --> 0:15:03.156 Then we have to make it silent to the immune 0:15:03.236 --> 0:15:08.756 system so our body doesn't recognize it. We have to 0:15:08.756 --> 0:15:12.196 make sure that it doesn't alter the viscosity of blood 0:15:12.356 --> 0:15:15.516 so it doesn't get too thick or too thin, and 0:15:15.516 --> 0:15:17.636 then we have to make sure it doesn't interact with 0:15:17.796 --> 0:15:21.516 the blood clotting system, it doesn't cause blood clots or 0:15:21.596 --> 0:15:24.556 interfere with blood clots. And then we have to make 0:15:24.596 --> 0:15:28.956 it freeze dry, and then you know, we have to 0:15:29.556 --> 0:15:33.156 make it circulate for a long time. We have to 0:15:33.196 --> 0:15:37.076 evade the body system for clearing things that shouldn't be 0:15:37.076 --> 0:15:38.636 in our blood out of our blood. 0:15:38.996 --> 0:15:40.636 And so once we solve all those. 0:15:40.436 --> 0:15:43.436 Things, you know, then you know now it's working in 0:15:43.956 --> 0:15:46.316 an animal model. And that's why the very first one 0:15:46.356 --> 0:15:50.236 didn't work because while doctor Pan had already figured out 0:15:50.236 --> 0:15:53.556 how to get hemoglobin inside the fat droplet, it didn't 0:15:53.596 --> 0:15:55.036 do any of these other things yet. 0:15:55.916 --> 0:15:58.116 So is there a moment when you decide, oh, we 0:15:58.156 --> 0:15:59.276 should start a company. 0:15:59.596 --> 0:16:03.436 Yes, and so we started the company when we had 0:16:03.516 --> 0:16:08.956 first demonstrated proof of concept that we could create art 0:16:09.156 --> 0:16:12.356 official red cell. At that point we have a different task. 0:16:12.956 --> 0:16:18.276 So the original academic task was can we design an 0:16:18.356 --> 0:16:22.596 artificial cell? Can we prove that it works. Once we've 0:16:22.636 --> 0:16:27.196 done that, we now have a development commercial development task, 0:16:27.276 --> 0:16:30.476 which is can we make it reliably? Can we make 0:16:30.516 --> 0:16:32.876 it over and over again? Can we make a lot 0:16:32.876 --> 0:16:36.636 of it? Can we make sure that it passes all 0:16:36.676 --> 0:16:39.516 the safety and efficacy criteria FDA. 0:16:40.196 --> 0:16:42.156 So that task we need a company for. 0:16:42.356 --> 0:16:45.036 It's very different than a university task, and that's when 0:16:45.036 --> 0:16:46.916 we formed Kalasite in. 0:16:46.876 --> 0:16:53.236 Order to do those things. We'll be back in just 0:16:53.276 --> 0:17:07.756 a minute. Right that in twenty twenty three, you've got 0:17:07.756 --> 0:17:11.716 a forty six million dollars DARPA grant we're part of that. 0:17:11.876 --> 0:17:13.756 Tell me about that. That seems like a big moment 0:17:13.836 --> 0:17:16.676 in the history of this project. That was the moment. Yeah, 0:17:19.236 --> 0:17:22.436 So we had been working on in a reasonably successful 0:17:22.436 --> 0:17:25.796 way developing the red blood cells, artificial red cells. 0:17:26.316 --> 0:17:31.116 But what DARPA wanted. DARPA wanted everything. They wanted all 0:17:31.156 --> 0:17:35.956 the function of blood, so the ability to clot. So 0:17:36.116 --> 0:17:40.476 for a soldier, i'd basically, if you need artificial red cells. 0:17:41.036 --> 0:17:42.196 It's because you're bleeding. 0:17:42.636 --> 0:17:47.756 By definition, If you just replace the red cells and 0:17:47.796 --> 0:17:52.876 you don't replace the clotting factor, then it's like pouring 0:17:53.516 --> 0:17:56.516 blood into a sieve. It just falls back out again. 0:17:57.236 --> 0:18:00.476 It's ineffective. So they realize that we need to be 0:18:00.516 --> 0:18:04.116 able to replace everything, and to do that at the 0:18:04.156 --> 0:18:07.156 point of injury, you need freeze tride plasma, you need 0:18:07.156 --> 0:18:11.236 freeze stride platelets, you need free stride red cells, and 0:18:11.516 --> 0:18:13.996 it has to be scalable, and you know, there are 0:18:13.996 --> 0:18:16.916 a lot of logistic concerns. So what they put out 0:18:16.916 --> 0:18:22.396 a call for applications for teams to form from the 0:18:22.436 --> 0:18:25.356 people who are working on each of those components, and 0:18:25.476 --> 0:18:28.756 everybody had just been working on them separately to come 0:18:28.796 --> 0:18:32.996 together and form a consortium that would figure out how 0:18:32.996 --> 0:18:38.076 to make all these different components compatible and equivalent. 0:18:37.556 --> 0:18:41.276 To stored blood. So we built a consortium to do 0:18:41.356 --> 0:18:45.356 that and we completed effectively to win that award. What 0:18:45.516 --> 0:18:48.316 is the status of the would you call it artificial 0:18:48.316 --> 0:18:50.356 whole blood? What do you call the whole package? 0:18:50.556 --> 0:18:53.156 Unfortunately, we don't have a very sexy name for it yet. 0:18:53.236 --> 0:18:56.396 We call it the whole blood analog. So you know, 0:18:56.436 --> 0:19:01.676 it's not completely artificial because it's a biologically derived PLASMI. 0:19:01.716 --> 0:19:05.716 It's just regular plasma that's been freeze stride. The platelets 0:19:05.716 --> 0:19:09.756 are fully synthetic, so they help, you know, form blood 0:19:09.756 --> 0:19:12.756 clots to stop the bleeding, to stop the bleeding, which 0:19:12.836 --> 0:19:15.316 is you know, that's why they're getting this material. 0:19:16.476 --> 0:19:19.756 And so we sort of have two threads going now, right, 0:19:19.756 --> 0:19:22.916 there's how is it going on your artificial red blood cells? 0:19:22.916 --> 0:19:25.196 And then how is the whole blood analog project going? 0:19:25.236 --> 0:19:27.796 So let's just take those in order, like, what is 0:19:27.836 --> 0:19:30.716 the status of the like, are you testing the artificial 0:19:30.756 --> 0:19:33.316 red blood cell on its own? In oh? Yes, in 0:19:33.356 --> 0:19:35.716 clinical trials. Is that part of the plan to do 0:19:35.756 --> 0:19:37.956 that by itself or do you does it need to 0:19:37.956 --> 0:19:38.956 be the whole package. 0:19:39.036 --> 0:19:43.356 Well, it has to be tested by itself first, and 0:19:43.796 --> 0:19:48.556 so as a standalone element. And so we are still 0:19:48.596 --> 0:19:52.396 in what's called pre clinical testing. So we're testing in 0:19:52.836 --> 0:19:59.316 animal models and in parallel we're developing the combined product 0:19:59.836 --> 0:20:05.396 which will be sequentially administered plasma two, carrier and platelet, 0:20:06.156 --> 0:20:08.316 and that's also in pre clinical testing. 0:20:08.676 --> 0:20:11.716 Two is the red blood cell is the red blood cell, 0:20:11.796 --> 0:20:16.516 that's right, and plasma and platelet and that is expected 0:20:16.596 --> 0:20:19.796 that will follow. So we have to first test each 0:20:19.876 --> 0:20:24.916 element by itself before we start mixing cocktails. That's so hard, 0:20:25.356 --> 0:20:28.836 Like I feel like the way fractional probabilities work. If 0:20:28.876 --> 0:20:31.476 a bunch of things have to work separately and there's 0:20:31.476 --> 0:20:34.556 some you know, the fractions multiply, right, so it gets 0:20:35.556 --> 0:20:39.076 less and less likely that'll work just probabilistically, right. But 0:20:39.236 --> 0:20:42.316 what we have the ability to do is adapt to 0:20:42.356 --> 0:20:44.956 what we find, and that's what we've had to do. 0:20:45.076 --> 0:20:47.996 So we took these components, and of course they didn't 0:20:48.036 --> 0:20:51.636 automatically work altogether, so we weren't able to just take 0:20:51.676 --> 0:20:54.076 the red blood cells and the plasma and the platelets 0:20:54.076 --> 0:20:56.756 and just put them in a blender and get blood. 0:20:57.036 --> 0:21:01.556 So we've had to tune. We're actually now on version 0:21:01.756 --> 0:21:04.796 four zero point one point two of the starting with 0:21:04.956 --> 0:21:08.476 version zero of the System of the. 0:21:08.396 --> 0:21:11.596 Whole Blood of the whole Blood analog. Yes, yeah, okay. 0:21:12.316 --> 0:21:14.476 And is it right that there are other groups? Is 0:21:14.476 --> 0:21:17.236 there a group in Japan working on something similar? Tell 0:21:17.236 --> 0:21:19.516 me about that, and tell me about the field more broadly, 0:21:19.596 --> 0:21:21.676 other similar projects. Sure. 0:21:21.996 --> 0:21:28.676 The other main encapsulated program is in Japan, led by 0:21:29.196 --> 0:21:34.076 a really successful scientists named Romi Sakai. 0:21:34.436 --> 0:21:38.596 He's been working on this for over a decade, developing 0:21:38.636 --> 0:21:41.796 another's It's. 0:21:41.636 --> 0:21:46.036 Essentially the same concept. It's a liposome with hemoglobin on 0:21:46.076 --> 0:21:49.156 the inside, a fat droplet, A fat droplet, Yeah right, 0:21:49.236 --> 0:21:52.436 it's a fat droplet, and it's a little different. It 0:21:52.476 --> 0:21:56.556 doesn't have that wetwear system that we talked about. He's 0:21:57.196 --> 0:22:01.196 adjusted the auction affinity to be sort of in the middle, 0:22:01.716 --> 0:22:04.356 so it's pretty good at capturing auction in the lung 0:22:04.436 --> 0:22:06.996 and pretty good at letting it go and tissue. It 0:22:07.036 --> 0:22:10.316 doesn't shift up and down depending on where it is, 0:22:10.396 --> 0:22:14.276 so it's good enough. It works and he's already begun 0:22:14.356 --> 0:22:17.556 to test its safety in humans. Now it's it's not 0:22:17.716 --> 0:22:22.276 freeze drive. It's still in water, and they are not 0:22:22.436 --> 0:22:25.316 working on combining it with plasma and platelets. 0:22:25.356 --> 0:22:28.196 It's just the two carrier. How do you think it's 0:22:28.236 --> 0:22:30.436 going that the Japanese version? 0:22:30.876 --> 0:22:34.276 Great, They're they're out in front, so they've they've tested 0:22:34.316 --> 0:22:37.956 in humans and they had some minor issues that I 0:22:37.956 --> 0:22:42.076 think have been probably been addressed in and it's incredibly exciting. 0:22:42.116 --> 0:22:45.316 We're all benefiting from doctor Sakai's leadership. 0:22:45.756 --> 0:22:48.196 So to return to your own work and the work 0:22:48.196 --> 0:22:51.116 of the consortium that you're part of, what's the happy story? 0:22:51.316 --> 0:22:54.076 Like how long in the future do you think about 0:22:54.196 --> 0:22:55.876 and what do you think about when you think about 0:22:55.916 --> 0:23:02.036 it going well? Uh So, if you think about it 0:23:02.076 --> 0:23:04.756 going well, I guess there's a presumption baked into that question. 0:23:05.196 --> 0:23:07.956 Mostly I think about, you know, how it's not going 0:23:07.996 --> 0:23:10.476 to go well? Okay, Well, how might it not go well? 0:23:10.476 --> 0:23:12.516 I mean I guess that one's easier to imagine in 0:23:12.516 --> 0:23:14.196 some ways, but how might it not go well? 0:23:14.596 --> 0:23:17.076 I Mean, what I'm really worried about is the things 0:23:17.116 --> 0:23:20.636 I can't imagine, So the things we imagine we're constantly 0:23:20.636 --> 0:23:21.196 trying to think. 0:23:21.116 --> 0:23:23.116 Of how it won't go well, and we try. 0:23:22.956 --> 0:23:26.876 To anticipate a solution to the problem and fix it. 0:23:26.996 --> 0:23:29.356 The things that we can't plan for, of course, are 0:23:29.356 --> 0:23:31.036 the things that we don't yet understand. 0:23:31.036 --> 0:23:35.316 The drums felled in unknowns. Yeah you beat me to it. 0:23:35.396 --> 0:23:40.996 Yeah yeah, so and that happens monthly, where it's like, uh, oh, 0:23:40.996 --> 0:23:43.116 we didn't think of that. Now we have to solve 0:23:43.116 --> 0:23:46.436