1 00:00:15,356 --> 00:00:23,636 Speaker 1: Pushkin. Every year, sixty thousand people in the United States 2 00:00:23,916 --> 00:00:27,516 Speaker 1: and two million people around the world die because of 3 00:00:27,596 --> 00:00:31,036 Speaker 1: blood loss. They get in a car accident, or they 4 00:00:31,036 --> 00:00:35,436 Speaker 1: get shot and they bleed to death. These people tend 5 00:00:35,436 --> 00:00:38,556 Speaker 1: to be relatively young and healthy, and a lot of 6 00:00:38,596 --> 00:00:41,316 Speaker 1: them could be saved if they were quickly given blood. 7 00:00:41,716 --> 00:00:45,796 Speaker 1: But outside the body, blood doesn't travel well. It's bulky. 8 00:00:46,076 --> 00:00:48,556 Speaker 1: You have to keep it cold, and as a result, 9 00:00:48,716 --> 00:00:52,036 Speaker 1: it's hard to get blood to patience when they urgently 10 00:00:52,196 --> 00:00:56,636 Speaker 1: need it. Ambulances don't tend to carry it. Field medics 11 00:00:56,636 --> 00:00:59,916 Speaker 1: don't typically have it in combat, and so there's long 12 00:00:59,956 --> 00:01:02,916 Speaker 1: been this dream. What if we could come up with 13 00:01:02,956 --> 00:01:06,636 Speaker 1: a way to make blood easier to store and transport. 14 00:01:07,396 --> 00:01:09,756 Speaker 1: What if we could have blood ready to go every 15 00:01:09,836 --> 00:01:12,436 Speaker 1: time an ambulance gets to a car accident and a 16 00:01:12,476 --> 00:01:15,516 Speaker 1: medic gets to a wounded soldier. If we could do that, 17 00:01:16,036 --> 00:01:25,996 Speaker 1: we could save millions of lives. I'm Jacob Goldstein and 18 00:01:25,996 --> 00:01:27,796 Speaker 1: this is What's Your Problem, the show where I talk 19 00:01:27,836 --> 00:01:31,036 Speaker 1: to people who are trying to make technological progress. My 20 00:01:31,116 --> 00:01:34,396 Speaker 1: guest today is Alan Doctor. He's the co founder and 21 00:01:34,476 --> 00:01:39,396 Speaker 1: chief scientific officer at Kalasite. Alan's problem is this, can 22 00:01:39,436 --> 00:01:43,276 Speaker 1: you make something like freeze dried blood that can be 23 00:01:43,516 --> 00:01:46,836 Speaker 1: rehydrated and given to patients when and where they need it. 24 00:01:47,916 --> 00:01:50,756 Speaker 1: Alan didn't start out wanting to found a company. He 25 00:01:50,836 --> 00:01:53,076 Speaker 1: was a doctor taking care of kids in the hospital. 26 00:01:53,556 --> 00:01:55,956 Speaker 2: So the type of medicine I do is intensive care 27 00:01:55,996 --> 00:02:00,036 Speaker 2: of medicine. So this is and for children, looking after 28 00:02:00,436 --> 00:02:04,556 Speaker 2: children in the hospital who have severe infections or major 29 00:02:04,636 --> 00:02:08,956 Speaker 2: injuries and they're critically ill, and most of them are 30 00:02:08,956 --> 00:02:12,436 Speaker 2: in something a condition we call shock. And the problem 31 00:02:12,556 --> 00:02:17,396 Speaker 2: with shock is that you're not effectively getting blood and 32 00:02:17,556 --> 00:02:22,436 Speaker 2: oxygen where it's needed. Okay, so people get sick and die. 33 00:02:22,876 --> 00:02:25,836 Speaker 2: Even though we fix the underlying problem, so we can 34 00:02:25,916 --> 00:02:29,556 Speaker 2: cure the infection, we repair the hole in the blood vessel, 35 00:02:30,116 --> 00:02:34,836 Speaker 2: and people still we lose them because their circulatory system 36 00:02:34,876 --> 00:02:35,476 Speaker 2: is failing. 37 00:02:35,836 --> 00:02:35,996 Speaker 1: You know. 38 00:02:36,076 --> 00:02:38,716 Speaker 2: That was frustrating, and I was interested in that problem 39 00:02:38,836 --> 00:02:41,196 Speaker 2: and I was trying to understand why that happened. And 40 00:02:41,356 --> 00:02:45,716 Speaker 2: what we were able to learn is there's a traffic 41 00:02:45,796 --> 00:02:50,716 Speaker 2: control system in our circulatory system that routes blood where 42 00:02:50,716 --> 00:02:54,596 Speaker 2: it needs to go, and red blood cells are the 43 00:02:54,636 --> 00:02:59,316 Speaker 2: traffic lights, so they turn green and they open up 44 00:02:59,316 --> 00:03:01,836 Speaker 2: the blood vessels or they turn red and close them, 45 00:03:01,996 --> 00:03:06,996 Speaker 2: and it's very coordinated. It's a very exquisitely tuned system. 46 00:03:07,156 --> 00:03:11,756 Speaker 2: And I was studying that, huh, that's governed by the 47 00:03:11,796 --> 00:03:16,756 Speaker 2: way hemoglobin interacts with other chemicals in our blood stream. 48 00:03:17,076 --> 00:03:20,756 Speaker 2: And it turns out it's highly relevant for shock and 49 00:03:20,836 --> 00:03:24,956 Speaker 2: fixing shock. But it turns out it's also relevant for transfusion. 50 00:03:25,356 --> 00:03:27,476 Speaker 2: And that's when this story started. 51 00:03:27,916 --> 00:03:31,316 Speaker 1: So you're studying red blood cells and hemoglobin, which are 52 00:03:31,356 --> 00:03:35,876 Speaker 1: obviously hemoglobin are the molecules that transport oxygen, right, that 53 00:03:35,956 --> 00:03:39,996 Speaker 1: do that key function of blood. That is the thing 54 00:03:40,236 --> 00:03:43,356 Speaker 1: in particular that you want to replace when somebody gets 55 00:03:43,356 --> 00:03:45,316 Speaker 1: shot or gets in a car accident. Right, of all 56 00:03:45,356 --> 00:03:47,396 Speaker 1: the things in your blood, the thing you need urgently 57 00:03:47,476 --> 00:03:51,756 Speaker 1: that minute is hemoglobin to deliver the oxygen right. Right. 58 00:03:51,796 --> 00:03:53,756 Speaker 1: People had known that part for a long time and 59 00:03:53,836 --> 00:03:58,476 Speaker 1: had tried to develop blood substitutes in particular to solve 60 00:03:58,476 --> 00:04:01,756 Speaker 1: this acute kind of trauma setting problem. But it had 61 00:04:01,796 --> 00:04:05,836 Speaker 1: gone badly right, So tell me about the history up 62 00:04:05,916 --> 00:04:09,036 Speaker 1: until that point of people trying to come up with 63 00:04:09,236 --> 00:04:12,636 Speaker 1: ways to you know, get hemoglobin to people in emergencies, 64 00:04:12,676 --> 00:04:14,396 Speaker 1: do sort of hemoglobin replacements. 65 00:04:15,036 --> 00:04:18,596 Speaker 2: Well, they did the first obvious thing. So the problem 66 00:04:18,716 --> 00:04:21,596 Speaker 2: is you have to make the bloodshelf stable in order 67 00:04:21,676 --> 00:04:25,876 Speaker 2: to use it outside of hospitals, So you have to 68 00:04:25,876 --> 00:04:29,036 Speaker 2: get rid of the cold chain. The reason we need 69 00:04:29,076 --> 00:04:32,876 Speaker 2: the cold chain is the hemoglobin's inside a red blood cell. 70 00:04:32,956 --> 00:04:37,116 Speaker 2: The red blood cell's alive, and it needs glucose, it 71 00:04:37,156 --> 00:04:40,076 Speaker 2: needs all kinds of things, and it has to be 72 00:04:40,196 --> 00:04:43,356 Speaker 2: kept colder. It goes bad, sort of like the way 73 00:04:43,396 --> 00:04:46,556 Speaker 2: milk has to be kept colder. It goes bad, and 74 00:04:46,716 --> 00:04:49,116 Speaker 2: you can't leave it outside the fridge too long or 75 00:04:49,276 --> 00:04:50,436 Speaker 2: you can't drink it. 76 00:04:50,556 --> 00:04:51,676 Speaker 1: The same thing with blood. 77 00:04:52,836 --> 00:04:55,156 Speaker 2: So they say, okay, if we just take the hemoglobin 78 00:04:55,196 --> 00:04:58,196 Speaker 2: out of the red cell, will it still capture and 79 00:04:58,236 --> 00:04:59,116 Speaker 2: release oxygen? 80 00:04:59,356 --> 00:05:02,836 Speaker 1: Yes, okay it will. So far, so good, So far, 81 00:05:02,916 --> 00:05:03,316 Speaker 1: so good. 82 00:05:03,676 --> 00:05:08,236 Speaker 2: Does it need to be kept cold in order to work, No, 83 00:05:08,596 --> 00:05:13,116 Speaker 2: it doesn't, So it's shelf stable. Doesn't work if we 84 00:05:13,156 --> 00:05:18,276 Speaker 2: put it inside animals. Pretty much it does, and so 85 00:05:18,636 --> 00:05:20,516 Speaker 2: everybody's like, okay, let's try this. 86 00:05:20,636 --> 00:05:20,836 Speaker 1: Yeah. 87 00:05:21,596 --> 00:05:25,276 Speaker 2: And it was a catastrophe, so it wasn't just ineffective. 88 00:05:25,316 --> 00:05:29,316 Speaker 2: It was harmful, so it was more harmful than the controls. 89 00:05:29,396 --> 00:05:32,956 Speaker 2: So it caused heart attacks and strokes and death in 90 00:05:33,036 --> 00:05:34,516 Speaker 2: the people that got the blood. 91 00:05:34,636 --> 00:05:37,236 Speaker 1: Why is it bad to give people hemoglobin? That is 92 00:05:37,276 --> 00:05:42,076 Speaker 1: a surprising outcome, right, It's not like it's some novel molecule. 93 00:05:42,156 --> 00:05:44,876 Speaker 1: It's our bodies are full of hemoglobin, all right. 94 00:05:44,956 --> 00:05:47,956 Speaker 2: So what it meant was we didn't understand something. It 95 00:05:47,996 --> 00:05:52,916 Speaker 2: turns out hemoglobin does more than just interact with oxygen. 96 00:05:52,996 --> 00:05:56,436 Speaker 2: It interacts with other chemicals in the blood stream. So 97 00:05:57,156 --> 00:06:00,836 Speaker 2: the hemoglobin has to be sheathed inside a membrane, and 98 00:06:00,916 --> 00:06:05,236 Speaker 2: it sequesters the hemoglobin from everything else in the blood stream, 99 00:06:05,716 --> 00:06:08,796 Speaker 2: from the blood vessels, the cells that line the blood vessel, 100 00:06:08,836 --> 00:06:13,556 Speaker 2: from the chemicals in the bloodstream where it won't do 101 00:06:13,716 --> 00:06:16,996 Speaker 2: things it's not supposed to do. And it turns out 102 00:06:17,276 --> 00:06:20,476 Speaker 2: that when hemoglobin is free in the bloodstream, the blood 103 00:06:20,556 --> 00:06:23,036 Speaker 2: vessels don't know whether they're to open or close, and 104 00:06:23,116 --> 00:06:25,396 Speaker 2: what they end up doing is mostly closing. 105 00:06:25,596 --> 00:06:29,196 Speaker 1: Uh huh. So that's why people who got just naked 106 00:06:29,236 --> 00:06:33,356 Speaker 1: hemoglobin had heart attacks. Basically exactly, yeah, exactly, got it. 107 00:06:33,476 --> 00:06:36,916 Speaker 1: So okay, So this is the context, right, So clear 108 00:06:37,716 --> 00:06:41,716 Speaker 1: bad idea to just give people hemoglobin. Alas well, it 109 00:06:41,756 --> 00:06:43,836 Speaker 1: was a good idea. It seemed like a good idea, 110 00:06:43,836 --> 00:06:45,796 Speaker 1: but it became clear that it had been a bad idea. 111 00:06:45,836 --> 00:06:48,476 Speaker 1: It's scary in fact, right, it scary like so many 112 00:06:48,596 --> 00:06:51,716 Speaker 1: things we've all done. Yeah, yeah, no, no, no shade 113 00:06:51,756 --> 00:06:54,116 Speaker 1: on the people who tried it. It's just a it's 114 00:06:54,156 --> 00:06:58,196 Speaker 1: a terrible outcome that nobody would have wanted. So you meanwhile, 115 00:06:58,276 --> 00:07:04,156 Speaker 1: are studying hemoglobin and then a chemical engineer comes to 116 00:07:04,196 --> 00:07:07,036 Speaker 1: you with an idea, Right, tell me about that. Twenty 117 00:07:07,196 --> 00:07:07,876 Speaker 1: ten what happened? 118 00:07:07,956 --> 00:07:11,756 Speaker 2: Yeah, I'm just studying regular red blood cells and this 119 00:07:12,076 --> 00:07:16,596 Speaker 2: routing problem, right, which I understood. That's why you know 120 00:07:16,876 --> 00:07:19,236 Speaker 2: a lot of these blood substitutes, what we call the 121 00:07:19,356 --> 00:07:23,996 Speaker 2: unencapsulated hemoglobins failed. People started to understand that, but I 122 00:07:24,076 --> 00:07:26,516 Speaker 2: wasn't thinking like, oh, I know how to solve that problem. 123 00:07:26,916 --> 00:07:30,476 Speaker 2: I was minding my own business doing something completely different. 124 00:07:30,756 --> 00:07:37,316 Speaker 2: The chemical engineer, the bioengineer was making special particles, nanoparticles 125 00:07:37,356 --> 00:07:42,596 Speaker 2: for imaging. So there's a new form of medicines and 126 00:07:42,676 --> 00:07:47,276 Speaker 2: therapies where you make little fat droplets and you can 127 00:07:47,356 --> 00:07:52,116 Speaker 2: decorate them with all kinds of molecules that either home 128 00:07:52,196 --> 00:07:54,236 Speaker 2: to different parts of your body, and you can see 129 00:07:54,276 --> 00:07:56,756 Speaker 2: them on X ray. You can put drugs inside, you 130 00:07:56,796 --> 00:07:58,316 Speaker 2: can do all kinds of things with them. 131 00:07:58,636 --> 00:08:00,956 Speaker 1: Well, just to be clear, these fat droplets, as you're 132 00:08:00,956 --> 00:08:05,116 Speaker 1: describing them, like, they were the technology used to encapsulate 133 00:08:05,236 --> 00:08:10,196 Speaker 1: the COVID vaccines, right, that's RNA covid vaccines were in 134 00:08:10,396 --> 00:08:12,796 Speaker 1: what lipid NAO particle is? That is the jargon, right, 135 00:08:12,836 --> 00:08:14,796 Speaker 1: although I like exactly I appreciate that. 136 00:08:14,876 --> 00:08:18,476 Speaker 2: Yeah, so yeah, liposomas was used for or a fat 137 00:08:18,556 --> 00:08:21,956 Speaker 2: droplet was used for the covid vaccine, and it's used 138 00:08:21,956 --> 00:08:26,716 Speaker 2: for other things too. So what doctor pan Depongen Pans 139 00:08:26,796 --> 00:08:32,956 Speaker 2: a brilliant chemical engineer. So he was making particles so 140 00:08:32,996 --> 00:08:36,076 Speaker 2: that you could see specific things. So you want to 141 00:08:36,116 --> 00:08:38,156 Speaker 2: be able to see breast cancer, You want to be 142 00:08:38,156 --> 00:08:41,116 Speaker 2: able to see a blood clot. You want to see, 143 00:08:41,276 --> 00:08:43,916 Speaker 2: you know, a particular type of cell. Then you put 144 00:08:43,956 --> 00:08:47,516 Speaker 2: something on a fat droplet that finds that cell, and 145 00:08:47,556 --> 00:08:50,836 Speaker 2: you put a little metal in the droplet that you 146 00:08:50,876 --> 00:08:55,156 Speaker 2: can see with a special CT scan and then say 147 00:08:55,236 --> 00:08:58,996 Speaker 2: suddenly I see very small and tiny, hard to detect 148 00:08:59,396 --> 00:09:02,836 Speaker 2: cancers and so on. So he was making these particles, 149 00:09:03,356 --> 00:09:05,516 Speaker 2: and he was doing them in a way he wanted 150 00:09:05,556 --> 00:09:08,316 Speaker 2: to make a lot of surface area, and he ended 151 00:09:08,396 --> 00:09:11,476 Speaker 2: up making particle that looked like red blood. 152 00:09:11,196 --> 00:09:14,796 Speaker 1: Cells just by happenstance. He just looked at it one 153 00:09:14,836 --> 00:09:17,276 Speaker 1: and said, hey, I know what that looks like a 154 00:09:17,316 --> 00:09:18,076 Speaker 1: red blood cell. 155 00:09:18,196 --> 00:09:21,156 Speaker 2: So red blood cells are also trying to have a 156 00:09:21,156 --> 00:09:24,636 Speaker 2: lot of surface area because they exchange gas, and he 157 00:09:24,756 --> 00:09:26,836 Speaker 2: was trying to create a lot of surface area for 158 00:09:26,876 --> 00:09:30,116 Speaker 2: a different reason, so he could decorate the particles with 159 00:09:30,196 --> 00:09:32,676 Speaker 2: these proteins, and then you get. 160 00:09:32,556 --> 00:09:34,396 Speaker 1: Red blood cells, said trying to think of what they 161 00:09:34,436 --> 00:09:36,876 Speaker 1: look like, and I thought of bali, which is kind 162 00:09:36,916 --> 00:09:41,236 Speaker 1: of a niche a niche analogy, right, like a bagel, 163 00:09:41,236 --> 00:09:43,596 Speaker 1: but with a thin doe part in where the hole 164 00:09:43,636 --> 00:09:45,676 Speaker 1: would be. Do you have a go to description of 165 00:09:45,716 --> 00:09:47,716 Speaker 1: a red blood cell? That's what we used. 166 00:09:47,756 --> 00:09:52,596 Speaker 2: They're called Nanobiali's no kidding, yes, or the other word 167 00:09:52,636 --> 00:09:55,316 Speaker 2: people say a biconcave disc Yeah. 168 00:09:55,196 --> 00:09:59,756 Speaker 1: That's less or less? Uh that's cool? Yes, okay, So 169 00:09:59,836 --> 00:10:02,716 Speaker 1: does he come to you with this, right, So what 170 00:10:03,036 --> 00:10:05,556 Speaker 1: happens He's like, Oh, that looks like a red blood cell. 171 00:10:05,596 --> 00:10:06,156 Speaker 1: What does he do? 172 00:10:06,836 --> 00:10:09,756 Speaker 2: So he thought, Hey, I want wonder if I could 173 00:10:09,756 --> 00:10:14,596 Speaker 2: put hemoglobin inside. And he was loosely familiar with the 174 00:10:14,716 --> 00:10:18,916 Speaker 2: problems with auction carriers and he says, I wonder if 175 00:10:18,916 --> 00:10:22,716 Speaker 2: I could just put hemoglobin inside, and he figured out 176 00:10:22,756 --> 00:10:25,756 Speaker 2: how to do that, and then he's like, I don't 177 00:10:25,796 --> 00:10:29,116 Speaker 2: know how to tell if this works or not. So so 178 00:10:28,836 --> 00:10:31,236 Speaker 2: we're both at wash YOU and wash You has this 179 00:10:31,356 --> 00:10:34,676 Speaker 2: collaboration website where you can google or it's. 180 00:10:34,476 --> 00:10:38,196 Speaker 1: Like googling, but it's just at WashU the university. Interesting 181 00:10:38,316 --> 00:10:40,636 Speaker 1: like an internal like an engine. 182 00:10:40,996 --> 00:10:46,276 Speaker 2: Yeah, so he searched red blood cell physiology and I 183 00:10:46,396 --> 00:10:49,396 Speaker 2: popped up. And so he called me and told me 184 00:10:49,476 --> 00:10:52,516 Speaker 2: the story and said, you know, why don't you come 185 00:10:52,516 --> 00:10:55,556 Speaker 2: over to my lab and and I'd like to show 186 00:10:55,556 --> 00:10:58,876 Speaker 2: you what we're doing and see if this works, and maybe. 187 00:10:58,636 --> 00:11:03,436 Speaker 1: We could figure out how to collaborate. Well it didn't work, huh, 188 00:11:03,476 --> 00:11:05,796 Speaker 1: But but wait, what do you mean it didn't work? 189 00:11:05,836 --> 00:11:07,036 Speaker 1: I was all ready for a to work. 190 00:11:07,116 --> 00:11:11,316 Speaker 2: What didn't Well, it's a little more to it than 191 00:11:11,356 --> 00:11:15,556 Speaker 2: just putting hemoglobein inside a fat droplet. So what I 192 00:11:15,636 --> 00:11:21,036 Speaker 2: realized is conceptually this would solve the problem that the 193 00:11:21,156 --> 00:11:26,356 Speaker 2: unencapsulated hemoglobins were plagued by this were like little red 194 00:11:26,396 --> 00:11:29,636 Speaker 2: blood cells. And if we could figure out the chemistry 195 00:11:29,676 --> 00:11:33,636 Speaker 2: to make this capture and release oxygen that maybe this 196 00:11:33,676 --> 00:11:36,596 Speaker 2: would you know, make things safe and and you can 197 00:11:36,676 --> 00:11:39,676 Speaker 2: freeze dry these things so they could be you know, 198 00:11:40,276 --> 00:11:42,636 Speaker 2: shelf stable and very lightweight. 199 00:11:42,996 --> 00:11:46,076 Speaker 1: So it's like instant coffee, but for red blood cells. 200 00:11:46,276 --> 00:11:51,036 Speaker 1: That's the dream. Yeah, yeah, exactly. So initially it doesn't work, 201 00:11:51,076 --> 00:11:56,476 Speaker 1: but you realize that the idea is fundamentally plausible. So 202 00:11:56,676 --> 00:11:59,676 Speaker 1: like one of the things you have to sort of 203 00:12:00,076 --> 00:12:01,916 Speaker 1: figure out make work for this. 204 00:12:02,356 --> 00:12:07,196 Speaker 2: Torque a number of things from the inside out. 205 00:12:07,556 --> 00:12:07,676 Speaker 1: OK. 206 00:12:07,716 --> 00:12:11,636 Speaker 2: So, first of all, you've got a droplet that has 207 00:12:11,676 --> 00:12:16,836 Speaker 2: hemoglobin inside it. Hemoglobin the reason red blood cells work. 208 00:12:16,876 --> 00:12:19,916 Speaker 2: There are a lot more than just bags of hemoglobin. 209 00:12:19,996 --> 00:12:24,396 Speaker 2: They have lots of other functions. And so we had 210 00:12:24,476 --> 00:12:27,036 Speaker 2: to decide what are we going to keep and what 211 00:12:27,076 --> 00:12:28,036 Speaker 2: do we get rid of? 212 00:12:28,316 --> 00:12:30,916 Speaker 1: Huh, Because you can't build the whole red blood cell. 213 00:12:30,956 --> 00:12:33,036 Speaker 1: We don't know how to do that. It's nice. You 214 00:12:33,276 --> 00:12:35,636 Speaker 1: want to do as little as you can get away with. 215 00:12:35,676 --> 00:12:40,716 Speaker 2: Right, right, You want the stripped down yeah, basic thing, 216 00:12:40,836 --> 00:12:43,996 Speaker 2: and so it just has to transport oxygen and then 217 00:12:44,076 --> 00:12:46,316 Speaker 2: it has to not do a bunch of other things. 218 00:12:46,356 --> 00:12:49,316 Speaker 1: Yeah, we don't want it to cause trouble either. Well 219 00:12:49,316 --> 00:12:52,556 Speaker 1: and subtly suddenly when you say transport oxygen. It has 220 00:12:52,596 --> 00:12:55,676 Speaker 1: to know when to pick up oxygen from the lungs 221 00:12:55,756 --> 00:12:58,036 Speaker 1: and has to know when to release oxygen to whatever 222 00:12:58,076 --> 00:13:02,156 Speaker 1: tissue needs it. Right, Like that part seems hard from 223 00:13:02,196 --> 00:13:06,596 Speaker 1: the outside, right, Well they're opposites. Yeah, yeah, and it 224 00:13:06,596 --> 00:13:08,756 Speaker 1: has to do it at the right time, right, it 225 00:13:08,756 --> 00:13:12,316 Speaker 1: has to do in the yes, at the right speed. 226 00:13:12,796 --> 00:13:16,036 Speaker 2: So yeah, it's all very finely tuned inside our body. 227 00:13:16,476 --> 00:13:19,076 Speaker 2: So we had to try to imitate the behavior of 228 00:13:19,076 --> 00:13:23,916 Speaker 2: a real red cell, and the real red cell has 229 00:13:24,276 --> 00:13:27,996 Speaker 2: people understand like, Okay, there are these other molecules inside 230 00:13:28,076 --> 00:13:32,276 Speaker 2: red cells that modify the way the hemoglobin interacts with 231 00:13:32,356 --> 00:13:37,636 Speaker 2: aucygen that causes it to capture oxygen effectively in the 232 00:13:37,716 --> 00:13:40,276 Speaker 2: lung and then let go when it gets out in 233 00:13:40,356 --> 00:13:44,236 Speaker 2: tissue and the red cells responding. Red cell doesn't know, 234 00:13:44,316 --> 00:13:47,236 Speaker 2: oh I'm in the lung, Oh I'm in the lip, 235 00:13:47,476 --> 00:13:54,156 Speaker 2: I'm in the muscle. So it's looking for cues. So 236 00:13:55,076 --> 00:13:58,276 Speaker 2: it doesn't have a map, but it can almost smell 237 00:13:58,356 --> 00:14:01,196 Speaker 2: where it is because of the chemicals that are different 238 00:14:01,236 --> 00:14:02,076 Speaker 2: in the lung. 239 00:14:02,236 --> 00:14:03,756 Speaker 1: Than in exercising muscle. 240 00:14:04,796 --> 00:14:08,316 Speaker 2: And it's primarily responding to the amount of acid and 241 00:14:08,356 --> 00:14:12,436 Speaker 2: the amount of carbon oxide that's in the blood. And 242 00:14:12,476 --> 00:14:18,316 Speaker 2: so what we did is we created responsive elements that 243 00:14:18,596 --> 00:14:22,236 Speaker 2: would work like red cells, but in a different way, 244 00:14:22,556 --> 00:14:27,436 Speaker 2: so that they would change their shape or change their 245 00:14:27,676 --> 00:14:31,756 Speaker 2: ability to interact with other molecules in response to those 246 00:14:31,796 --> 00:14:37,236 Speaker 2: two signals carbon dioxide and acid. So then the artificial 247 00:14:37,276 --> 00:14:40,756 Speaker 2: red cell quote knows it's in the lung or knows 248 00:14:40,796 --> 00:14:44,236 Speaker 2: it's in the muscle. So we call that wetwear. So 249 00:14:44,316 --> 00:14:50,596 Speaker 2: it's like a thousand little thermostats inside each little particle, 250 00:14:51,076 --> 00:14:53,596 Speaker 2: and it's telling the hemoglobin what to do. 251 00:14:53,956 --> 00:14:55,436 Speaker 1: I'm sure there are a lot of hard parts, but 252 00:14:55,516 --> 00:14:56,796 Speaker 1: that sounds like the hard part. 253 00:14:57,036 --> 00:14:59,996 Speaker 2: Well that was, Yeah, that was one of the hard right. 254 00:15:00,076 --> 00:15:03,156 Speaker 2: Then we have to make it silent to the immune 255 00:15:03,236 --> 00:15:08,756 Speaker 2: system so our body doesn't recognize it. We have to 256 00:15:08,756 --> 00:15:12,196 Speaker 2: make sure that it doesn't alter the viscosity of blood 257 00:15:12,356 --> 00:15:15,516 Speaker 2: so it doesn't get too thick or too thin, and 258 00:15:15,516 --> 00:15:17,636 Speaker 2: then we have to make sure it doesn't interact with 259 00:15:17,796 --> 00:15:21,516 Speaker 2: the blood clotting system, it doesn't cause blood clots or 260 00:15:21,596 --> 00:15:24,556 Speaker 2: interfere with blood clots. And then we have to make 261 00:15:24,596 --> 00:15:28,956 Speaker 2: it freeze dry, and then you know, we have to 262 00:15:29,556 --> 00:15:33,156 Speaker 2: make it circulate for a long time. We have to 263 00:15:33,196 --> 00:15:37,076 Speaker 2: evade the body system for clearing things that shouldn't be 264 00:15:37,076 --> 00:15:38,636 Speaker 2: in our blood out of our blood. 265 00:15:38,996 --> 00:15:40,636 Speaker 1: And so once we solve all those. 266 00:15:40,436 --> 00:15:43,436 Speaker 2: Things, you know, then you know now it's working in 267 00:15:43,956 --> 00:15:46,316 Speaker 2: an animal model. And that's why the very first one 268 00:15:46,356 --> 00:15:50,236 Speaker 2: didn't work because while doctor Pan had already figured out 269 00:15:50,236 --> 00:15:53,556 Speaker 2: how to get hemoglobin inside the fat droplet, it didn't 270 00:15:53,596 --> 00:15:55,036 Speaker 2: do any of these other things yet. 271 00:15:55,916 --> 00:15:58,116 Speaker 1: So is there a moment when you decide, oh, we 272 00:15:58,156 --> 00:15:59,276 Speaker 1: should start a company. 273 00:15:59,596 --> 00:16:03,436 Speaker 2: Yes, and so we started the company when we had 274 00:16:03,516 --> 00:16:08,956 Speaker 2: first demonstrated proof of concept that we could create art 275 00:16:09,156 --> 00:16:12,356 Speaker 2: official red cell. At that point we have a different task. 276 00:16:12,956 --> 00:16:18,276 Speaker 2: So the original academic task was can we design an 277 00:16:18,356 --> 00:16:22,596 Speaker 2: artificial cell? Can we prove that it works. Once we've 278 00:16:22,636 --> 00:16:27,196 Speaker 2: done that, we now have a development commercial development task, 279 00:16:27,276 --> 00:16:30,476 Speaker 2: which is can we make it reliably? Can we make 280 00:16:30,516 --> 00:16:32,876 Speaker 2: it over and over again? Can we make a lot 281 00:16:32,876 --> 00:16:36,636 Speaker 2: of it? Can we make sure that it passes all 282 00:16:36,676 --> 00:16:39,516 Speaker 2: the safety and efficacy criteria FDA. 283 00:16:40,196 --> 00:16:42,156 Speaker 1: So that task we need a company for. 284 00:16:42,356 --> 00:16:45,036 Speaker 2: It's very different than a university task, and that's when 285 00:16:45,036 --> 00:16:46,916 Speaker 2: we formed Kalasite in. 286 00:16:46,876 --> 00:16:53,236 Speaker 1: Order to do those things. We'll be back in just 287 00:16:53,276 --> 00:17:07,756 Speaker 1: a minute. Right that in twenty twenty three, you've got 288 00:17:07,756 --> 00:17:11,716 Speaker 1: a forty six million dollars DARPA grant we're part of that. 289 00:17:11,876 --> 00:17:13,756 Speaker 1: Tell me about that. That seems like a big moment 290 00:17:13,836 --> 00:17:16,676 Speaker 1: in the history of this project. That was the moment. Yeah, 291 00:17:19,236 --> 00:17:22,436 Speaker 1: So we had been working on in a reasonably successful 292 00:17:22,436 --> 00:17:25,796 Speaker 1: way developing the red blood cells, artificial red cells. 293 00:17:26,316 --> 00:17:31,116 Speaker 2: But what DARPA wanted. DARPA wanted everything. They wanted all 294 00:17:31,156 --> 00:17:35,956 Speaker 2: the function of blood, so the ability to clot. So 295 00:17:36,116 --> 00:17:40,476 Speaker 2: for a soldier, i'd basically, if you need artificial red cells. 296 00:17:41,036 --> 00:17:42,196 Speaker 1: It's because you're bleeding. 297 00:17:42,636 --> 00:17:47,756 Speaker 2: By definition, If you just replace the red cells and 298 00:17:47,796 --> 00:17:52,876 Speaker 2: you don't replace the clotting factor, then it's like pouring 299 00:17:53,516 --> 00:17:56,516 Speaker 2: blood into a sieve. It just falls back out again. 300 00:17:57,236 --> 00:18:00,476 Speaker 2: It's ineffective. So they realize that we need to be 301 00:18:00,516 --> 00:18:04,116 Speaker 2: able to replace everything, and to do that at the 302 00:18:04,156 --> 00:18:07,156 Speaker 2: point of injury, you need freeze tride plasma, you need 303 00:18:07,156 --> 00:18:11,236 Speaker 2: freeze stride platelets, you need free stride red cells, and 304 00:18:11,516 --> 00:18:13,996 Speaker 2: it has to be scalable, and you know, there are 305 00:18:13,996 --> 00:18:16,916 Speaker 2: a lot of logistic concerns. So what they put out 306 00:18:16,916 --> 00:18:22,396 Speaker 2: a call for applications for teams to form from the 307 00:18:22,436 --> 00:18:25,356 Speaker 2: people who are working on each of those components, and 308 00:18:25,476 --> 00:18:28,756 Speaker 2: everybody had just been working on them separately to come 309 00:18:28,796 --> 00:18:32,996 Speaker 2: together and form a consortium that would figure out how 310 00:18:32,996 --> 00:18:38,076 Speaker 2: to make all these different components compatible and equivalent. 311 00:18:37,556 --> 00:18:41,276 Speaker 1: To stored blood. So we built a consortium to do 312 00:18:41,356 --> 00:18:45,356 Speaker 1: that and we completed effectively to win that award. What 313 00:18:45,516 --> 00:18:48,316 Speaker 1: is the status of the would you call it artificial 314 00:18:48,316 --> 00:18:50,356 Speaker 1: whole blood? What do you call the whole package? 315 00:18:50,556 --> 00:18:53,156 Speaker 2: Unfortunately, we don't have a very sexy name for it yet. 316 00:18:53,236 --> 00:18:56,396 Speaker 2: We call it the whole blood analog. So you know, 317 00:18:56,436 --> 00:19:01,676 Speaker 2: it's not completely artificial because it's a biologically derived PLASMI. 318 00:19:01,716 --> 00:19:05,716 Speaker 2: It's just regular plasma that's been freeze stride. The platelets 319 00:19:05,716 --> 00:19:09,756 Speaker 2: are fully synthetic, so they help, you know, form blood 320 00:19:09,756 --> 00:19:12,756 Speaker 2: clots to stop the bleeding, to stop the bleeding, which 321 00:19:12,836 --> 00:19:15,316 Speaker 2: is you know, that's why they're getting this material. 322 00:19:16,476 --> 00:19:19,756 Speaker 1: And so we sort of have two threads going now, right, 323 00:19:19,756 --> 00:19:22,916 Speaker 1: there's how is it going on your artificial red blood cells? 324 00:19:22,916 --> 00:19:25,196 Speaker 1: And then how is the whole blood analog project going? 325 00:19:25,236 --> 00:19:27,796 Speaker 1: So let's just take those in order, like, what is 326 00:19:27,836 --> 00:19:30,716 Speaker 1: the status of the like, are you testing the artificial 327 00:19:30,756 --> 00:19:33,316 Speaker 1: red blood cell on its own? In oh? Yes, in 328 00:19:33,356 --> 00:19:35,716 Speaker 1: clinical trials. Is that part of the plan to do 329 00:19:35,756 --> 00:19:37,956 Speaker 1: that by itself or do you does it need to 330 00:19:37,956 --> 00:19:38,956 Speaker 1: be the whole package. 331 00:19:39,036 --> 00:19:43,356 Speaker 2: Well, it has to be tested by itself first, and 332 00:19:43,796 --> 00:19:48,556 Speaker 2: so as a standalone element. And so we are still 333 00:19:48,596 --> 00:19:52,396 Speaker 2: in what's called pre clinical testing. So we're testing in 334 00:19:52,836 --> 00:19:59,316 Speaker 2: animal models and in parallel we're developing the combined product 335 00:19:59,836 --> 00:20:05,396 Speaker 2: which will be sequentially administered plasma two, carrier and platelet, 336 00:20:06,156 --> 00:20:08,316 Speaker 2: and that's also in pre clinical testing. 337 00:20:08,676 --> 00:20:11,716 Speaker 1: Two is the red blood cell is the red blood cell, 338 00:20:11,796 --> 00:20:16,516 Speaker 1: that's right, and plasma and platelet and that is expected 339 00:20:16,596 --> 00:20:19,796 Speaker 1: that will follow. So we have to first test each 340 00:20:19,876 --> 00:20:24,916 Speaker 1: element by itself before we start mixing cocktails. That's so hard, 341 00:20:25,356 --> 00:20:28,836 Speaker 1: Like I feel like the way fractional probabilities work. If 342 00:20:28,876 --> 00:20:31,476 Speaker 1: a bunch of things have to work separately and there's 343 00:20:31,476 --> 00:20:34,556 Speaker 1: some you know, the fractions multiply, right, so it gets 344 00:20:35,556 --> 00:20:39,076 Speaker 1: less and less likely that'll work just probabilistically, right. But 345 00:20:39,236 --> 00:20:42,316 Speaker 1: what we have the ability to do is adapt to 346 00:20:42,356 --> 00:20:44,956 Speaker 1: what we find, and that's what we've had to do. 347 00:20:45,076 --> 00:20:47,996 Speaker 1: So we took these components, and of course they didn't 348 00:20:48,036 --> 00:20:51,636 Speaker 1: automatically work altogether, so we weren't able to just take 349 00:20:51,676 --> 00:20:54,076 Speaker 1: the red blood cells and the plasma and the platelets 350 00:20:54,076 --> 00:20:56,756 Speaker 1: and just put them in a blender and get blood. 351 00:20:57,036 --> 00:21:01,556 Speaker 2: So we've had to tune. We're actually now on version 352 00:21:01,756 --> 00:21:04,796 Speaker 2: four zero point one point two of the starting with 353 00:21:04,956 --> 00:21:08,476 Speaker 2: version zero of the System of the. 354 00:21:08,396 --> 00:21:11,596 Speaker 1: Whole Blood of the whole Blood analog. Yes, yeah, okay. 355 00:21:12,316 --> 00:21:14,476 Speaker 1: And is it right that there are other groups? Is 356 00:21:14,476 --> 00:21:17,236 Speaker 1: there a group in Japan working on something similar? Tell 357 00:21:17,236 --> 00:21:19,516 Speaker 1: me about that, and tell me about the field more broadly, 358 00:21:19,596 --> 00:21:21,676 Speaker 1: other similar projects. Sure. 359 00:21:21,996 --> 00:21:28,676 Speaker 2: The other main encapsulated program is in Japan, led by 360 00:21:29,196 --> 00:21:34,076 Speaker 2: a really successful scientists named Romi Sakai. 361 00:21:34,436 --> 00:21:38,596 Speaker 1: He's been working on this for over a decade, developing 362 00:21:38,636 --> 00:21:41,796 Speaker 1: another's It's. 363 00:21:41,636 --> 00:21:46,036 Speaker 2: Essentially the same concept. It's a liposome with hemoglobin on 364 00:21:46,076 --> 00:21:49,156 Speaker 2: the inside, a fat droplet, A fat droplet, Yeah right, 365 00:21:49,236 --> 00:21:52,436 Speaker 2: it's a fat droplet, and it's a little different. It 366 00:21:52,476 --> 00:21:56,556 Speaker 2: doesn't have that wetwear system that we talked about. He's 367 00:21:57,196 --> 00:22:01,196 Speaker 2: adjusted the auction affinity to be sort of in the middle, 368 00:22:01,716 --> 00:22:04,356 Speaker 2: so it's pretty good at capturing auction in the lung 369 00:22:04,436 --> 00:22:06,996 Speaker 2: and pretty good at letting it go and tissue. It 370 00:22:07,036 --> 00:22:10,316 Speaker 2: doesn't shift up and down depending on where it is, 371 00:22:10,396 --> 00:22:14,276 Speaker 2: so it's good enough. It works and he's already begun 372 00:22:14,356 --> 00:22:17,556 Speaker 2: to test its safety in humans. Now it's it's not 373 00:22:17,716 --> 00:22:22,276 Speaker 2: freeze drive. It's still in water, and they are not 374 00:22:22,436 --> 00:22:25,316 Speaker 2: working on combining it with plasma and platelets. 375 00:22:25,356 --> 00:22:28,196 Speaker 1: It's just the two carrier. How do you think it's 376 00:22:28,236 --> 00:22:30,436 Speaker 1: going that the Japanese version? 377 00:22:30,876 --> 00:22:34,276 Speaker 2: Great, They're they're out in front, so they've they've tested 378 00:22:34,316 --> 00:22:37,956 Speaker 2: in humans and they had some minor issues that I 379 00:22:37,956 --> 00:22:42,076 Speaker 2: think have been probably been addressed in and it's incredibly exciting. 380 00:22:42,116 --> 00:22:45,316 Speaker 2: We're all benefiting from doctor Sakai's leadership. 381 00:22:45,756 --> 00:22:48,196 Speaker 1: So to return to your own work and the work 382 00:22:48,196 --> 00:22:51,116 Speaker 1: of the consortium that you're part of, what's the happy story? 383 00:22:51,316 --> 00:22:54,076 Speaker 1: Like how long in the future do you think about 384 00:22:54,196 --> 00:22:55,876 Speaker 1: and what do you think about when you think about 385 00:22:55,916 --> 00:23:02,036 Speaker 1: it going well? Uh So, if you think about it 386 00:23:02,076 --> 00:23:04,756 Speaker 1: going well, I guess there's a presumption baked into that question. 387 00:23:05,196 --> 00:23:07,956 Speaker 1: Mostly I think about, you know, how it's not going 388 00:23:07,996 --> 00:23:10,476 Speaker 1: to go well? Okay, Well, how might it not go well? 389 00:23:10,476 --> 00:23:12,516 Speaker 1: I mean I guess that one's easier to imagine in 390 00:23:12,516 --> 00:23:14,196 Speaker 1: some ways, but how might it not go well? 391 00:23:14,596 --> 00:23:17,076 Speaker 2: I Mean, what I'm really worried about is the things 392 00:23:17,116 --> 00:23:20,636 Speaker 2: I can't imagine, So the things we imagine we're constantly 393 00:23:20,636 --> 00:23:21,196 Speaker 2: trying to think. 394 00:23:21,116 --> 00:23:23,116 Speaker 1: Of how it won't go well, and we try. 395 00:23:22,956 --> 00:23:26,876 Speaker 2: To anticipate a solution to the problem and fix it. 396 00:23:26,996 --> 00:23:29,356 Speaker 2: The things that we can't plan for, of course, are 397 00:23:29,356 --> 00:23:31,036 Speaker 2: the things that we don't yet understand. 398 00:23:31,036 --> 00:23:35,316 Speaker 1: The drums felled in unknowns. Yeah you beat me to it. 399 00:23:35,396 --> 00:23:40,996 Speaker 2: Yeah yeah, so and that happens monthly, where it's like, uh, oh, 400 00:23:40,996 --> 00:23:43,116 Speaker 2: we didn't think of that. Now we have to solve 401 00:23:43,116 --> 00:23:46,436 Speaker 2: a new problem because we're off the map, you know, 402 00:23:46,516 --> 00:23:48,756 Speaker 2: we don't really nobody's been. 403 00:23:48,556 --> 00:23:51,756 Speaker 1: Here before, so we have to figure those things out. 404 00:23:52,036 --> 00:23:55,996 Speaker 1: Does it seem impossibly hard? Like, frankly, this one, this 405 00:23:56,076 --> 00:24:01,236 Speaker 1: project just seems so hard, right, It is hard. If 406 00:24:01,276 --> 00:24:02,996 Speaker 1: it were easy, it'd be done already. 407 00:24:03,116 --> 00:24:06,236 Speaker 2: But the wonderful thing is that I think that we 408 00:24:06,716 --> 00:24:09,076 Speaker 2: have all the tools that we need to solve the problem. 409 00:24:09,876 --> 00:24:14,956 Speaker 2: So the advances in synthetic chemistry are impossible to overstate. 410 00:24:15,556 --> 00:24:21,796 Speaker 2: The advances in nanomedicine and nanofabrication are allowing us to 411 00:24:21,876 --> 00:24:25,916 Speaker 2: respond in very quick ways. The ability to use machine 412 00:24:25,996 --> 00:24:30,196 Speaker 2: learning and artificial intelligence to improve our design is reducing 413 00:24:30,236 --> 00:24:33,436 Speaker 2: the need to do thousands and thousands of experiments, so 414 00:24:34,356 --> 00:24:38,876 Speaker 2: we can use the computers to tell us the likely 415 00:24:38,956 --> 00:24:43,756 Speaker 2: things to work, and it reduces the empiric burden. And 416 00:24:44,116 --> 00:24:49,356 Speaker 2: we've got great resources because the NIH and Department of 417 00:24:49,396 --> 00:24:54,196 Speaker 2: Defense DARPA put a lot of resources in our hands. 418 00:24:54,316 --> 00:24:59,596 Speaker 2: So we're very fortunate that we can very quickly respond 419 00:25:00,356 --> 00:25:04,116 Speaker 2: to the problems that we encounter. So it works very 420 00:25:04,156 --> 00:25:07,636 Speaker 2: effectively in the models that we have. But now we 421 00:25:07,676 --> 00:25:13,036 Speaker 2: also have to make this scale. So that's another huge challenge. 422 00:25:13,516 --> 00:25:15,956 Speaker 2: So we have to go from making what you might 423 00:25:15,996 --> 00:25:17,876 Speaker 2: call craft beer to Budweiser. 424 00:25:18,796 --> 00:25:21,996 Speaker 1: And just to be clear, it's made from real blood, right, 425 00:25:22,076 --> 00:25:27,636 Speaker 1: Like the humoglobin in your lipid nanoparticles is hemoglobin from people, right, 426 00:25:27,716 --> 00:25:31,636 Speaker 1: It's not synthesized. So that is a scale challenge right there, Right, 427 00:25:32,076 --> 00:25:32,956 Speaker 1: that's impossible. 428 00:25:33,236 --> 00:25:37,756 Speaker 2: Right, So we can't synthesize hemoglobin from amino acids. That 429 00:25:38,116 --> 00:25:42,956 Speaker 2: is beyond our current capability, but we can program other 430 00:25:43,156 --> 00:25:44,716 Speaker 2: organisms to make it for. 431 00:25:44,676 --> 00:25:48,116 Speaker 1: Us, like yeast. Ideally yeast right put it in a 432 00:25:48,156 --> 00:25:50,956 Speaker 1: fact is that the yeah, we're going to brew it. 433 00:25:51,036 --> 00:25:55,156 Speaker 2: So we have a Yeast project where we are training 434 00:25:55,236 --> 00:25:58,676 Speaker 2: yeast to make human hemoglobin and to secrete it, and 435 00:25:59,156 --> 00:26:01,556 Speaker 2: that will eventually be our source. 436 00:26:02,276 --> 00:26:05,076 Speaker 1: So okay, So take thirty seconds off of thinking about 437 00:26:05,116 --> 00:26:06,676 Speaker 1: all the things that can go wrong and that you 438 00:26:06,716 --> 00:26:08,956 Speaker 1: have to figure out, and just tell me if some 439 00:26:09,636 --> 00:26:12,756 Speaker 1: you or the people who come after you even respectfully 440 00:26:13,436 --> 00:26:15,276 Speaker 1: figure out how to do all the things you're trying 441 00:26:15,316 --> 00:26:17,196 Speaker 1: to do, what will it look like? What will it 442 00:26:17,236 --> 00:26:18,076 Speaker 1: look like? Right? 443 00:26:18,596 --> 00:26:21,516 Speaker 2: Well, we actually believe it or not have done that. 444 00:26:21,556 --> 00:26:25,516 Speaker 2: We have a prototype of the delivery system. We've been 445 00:26:25,556 --> 00:26:29,196 Speaker 2: simultaneously trying to work with the people who would be 446 00:26:29,316 --> 00:26:31,916 Speaker 2: using it so that we don't end up with an 447 00:26:32,036 --> 00:26:34,956 Speaker 2: end product. And they say, but did you think about X? 448 00:26:34,996 --> 00:26:37,356 Speaker 2: And we just like, uh, So. 449 00:26:37,396 --> 00:26:39,876 Speaker 1: A person gets in a car accident or a soldier 450 00:26:39,876 --> 00:26:44,036 Speaker 1: gets shot on the battlefield, what happens in this future 451 00:26:44,076 --> 00:26:45,916 Speaker 1: where the thing you're working on works. 452 00:26:46,396 --> 00:26:49,356 Speaker 2: So what they'll have is a kit, and in the 453 00:26:49,436 --> 00:26:53,556 Speaker 2: kit will be three components, the two carrier, the plasma, 454 00:26:53,596 --> 00:26:56,916 Speaker 2: and the platelet. All of them will be dry powders. Okay, 455 00:26:57,596 --> 00:27:00,516 Speaker 2: So the instructions that we got from the Department of 456 00:27:00,556 --> 00:27:03,316 Speaker 2: Defense were it has to work in the dark, in 457 00:27:03,396 --> 00:27:06,996 Speaker 2: a ditch, under fire, and it has to be usable 458 00:27:07,116 --> 00:27:11,916 Speaker 2: by somebody who has basically known medical training. So that's 459 00:27:11,956 --> 00:27:15,996 Speaker 2: basically you know, not a sophisticated nurse or a scientist. 460 00:27:16,076 --> 00:27:18,676 Speaker 1: Basically, they want you to make instant coffee, but for blood. 461 00:27:18,876 --> 00:27:23,476 Speaker 2: But for blood, but also it's instant coffee. It's too complicated. 462 00:27:23,676 --> 00:27:26,636 Speaker 2: You've got to heat the water, you've got to dispense 463 00:27:26,716 --> 00:27:29,316 Speaker 2: it from a jar into a cup. 464 00:27:29,036 --> 00:27:32,236 Speaker 1: And pour the water. You can't do any of that. 465 00:27:32,956 --> 00:27:36,956 Speaker 2: So what we have is a system that has a 466 00:27:37,036 --> 00:27:40,196 Speaker 2: split bag with a dry side and a wet side 467 00:27:40,556 --> 00:27:43,956 Speaker 2: and something called a weak weld. So when it's folded over, 468 00:27:44,076 --> 00:27:47,076 Speaker 2: you can stand on it and it won't open. But 469 00:27:47,156 --> 00:27:51,236 Speaker 2: when you unfold it, you squeeze it and it pops 470 00:27:51,236 --> 00:27:55,516 Speaker 2: and the water migrates from one side to the other 471 00:27:55,636 --> 00:28:01,116 Speaker 2: and hydrates the dry material, and then it slashes around 472 00:28:01,116 --> 00:28:03,596 Speaker 2: in there for about a minute, and then you hang 473 00:28:03,676 --> 00:28:07,236 Speaker 2: it and you can use it just like a unit 474 00:28:07,276 --> 00:28:07,716 Speaker 2: of blood. 475 00:28:07,876 --> 00:28:09,516 Speaker 1: Right, you hang it like a like a ba that 476 00:28:09,556 --> 00:28:10,836 Speaker 1: goes into your arm on an. 477 00:28:10,796 --> 00:28:14,276 Speaker 2: Iterate, And there's one like that for the plasma and 478 00:28:14,276 --> 00:28:17,236 Speaker 2: the platelet's a little different because it's a much smaller volume. 479 00:28:17,356 --> 00:28:21,876 Speaker 2: That eventually will be what's called an autoinjector. Everybody's seen EpiPens, 480 00:28:22,476 --> 00:28:26,436 Speaker 2: so it'll be like an EpiPen. Now there's an additional problem. 481 00:28:26,916 --> 00:28:32,396 Speaker 2: Damn yes, there's two other problems really. So one is 482 00:28:32,836 --> 00:28:36,596 Speaker 2: for it to be shelf stable, it can't interact with 483 00:28:37,596 --> 00:28:43,036 Speaker 2: oxygen in the air. So water and iron and oxygen 484 00:28:43,156 --> 00:28:44,116 Speaker 2: equals rust. 485 00:28:44,596 --> 00:28:48,396 Speaker 1: Yeah, when you think about hemoglobin, it seems like rust, right, hemoglobin. 486 00:28:48,436 --> 00:28:51,396 Speaker 1: It's iron in the hemoglobin that is binding to the oxygen. Right, 487 00:28:51,396 --> 00:28:54,636 Speaker 1: And I'm like, wait, is hemoglobin just rusting all the time? 488 00:28:54,716 --> 00:28:55,916 Speaker 1: In my blood? Is going? 489 00:28:55,916 --> 00:28:59,876 Speaker 2: In fact, right now your hemoglobin is rusting about ten 490 00:28:59,956 --> 00:29:04,316 Speaker 2: percent of it is rusting constantly. But you have a 491 00:29:04,396 --> 00:29:08,476 Speaker 2: rust remover inside your red blood cells. That is, every 492 00:29:08,556 --> 00:29:11,396 Speaker 2: time it goes around, there's a little molecule in there 493 00:29:11,476 --> 00:29:15,716 Speaker 2: that's scrubbing the rust and demolishing the polishing the iron. 494 00:29:16,156 --> 00:29:18,436 Speaker 2: So we have to we have to prevent that from 495 00:29:18,516 --> 00:29:21,316 Speaker 2: happening during storage. And to do that, we have to 496 00:29:21,356 --> 00:29:26,116 Speaker 2: have a plastic soft plastic, but that has glass like properties, 497 00:29:26,596 --> 00:29:29,036 Speaker 2: so it doesn't allow water or oxygen through it. 498 00:29:29,116 --> 00:29:30,556 Speaker 1: And so that's a very. 499 00:29:30,356 --> 00:29:34,476 Speaker 2: Novel film that we are applying for the first time 500 00:29:34,596 --> 00:29:40,396 Speaker 2: to blood storage. The other problem is it can't be cold. 501 00:29:40,756 --> 00:29:43,716 Speaker 2: So I don't know if you've ever tried to hydrate 502 00:29:44,196 --> 00:29:48,156 Speaker 2: freez strike coffee with tapwater, it just makes clumps. It 503 00:29:48,196 --> 00:29:51,676 Speaker 2: doesn't it doesn't hydrate, so we actually have to warm it. 504 00:29:52,476 --> 00:29:53,596 Speaker 1: So we have to. 505 00:29:53,556 --> 00:29:56,796 Speaker 2: Build a heater into the bag system. So this is 506 00:29:56,876 --> 00:30:00,796 Speaker 2: another layer of plastic that has a little circuit inside, 507 00:30:01,516 --> 00:30:04,356 Speaker 2: and the circuit, when you turn it on, it will 508 00:30:04,876 --> 00:30:08,836 Speaker 2: warm the liquid and then it will turn color and 509 00:30:08,876 --> 00:30:11,116 Speaker 2: then the medic will know, okay, I can squeeze it. 510 00:30:11,276 --> 00:30:13,316 Speaker 2: And all the medic has to do is tear it open, 511 00:30:13,996 --> 00:30:17,076 Speaker 2: unfold the bag, wait for it to change color, squeeze it, 512 00:30:17,676 --> 00:30:19,596 Speaker 2: slash it a bit, and then hang it. 513 00:30:19,876 --> 00:30:22,596 Speaker 1: And that's the way it will work. That's the user 514 00:30:22,676 --> 00:30:25,036 Speaker 1: manual version of how it will work. What's the like 515 00:30:26,276 --> 00:30:30,116 Speaker 1: thirty thousand foot version of like just at a macro level, 516 00:30:30,116 --> 00:30:31,956 Speaker 1: somebody who didn't know what was going on, Like what 517 00:30:31,996 --> 00:30:33,756 Speaker 1: would they see and how would the world be different 518 00:30:33,836 --> 00:30:34,796 Speaker 1: if this works? 519 00:30:35,436 --> 00:30:37,716 Speaker 2: Well, first of all, every soldier would carry this in 520 00:30:37,756 --> 00:30:41,876 Speaker 2: their cargo pants, so they would have their own blood 521 00:30:42,356 --> 00:30:45,036 Speaker 2: instead of a blood tag that like now it just 522 00:30:45,076 --> 00:30:48,516 Speaker 2: says i'm typo, I'm type whatever. They actually have what 523 00:30:48,596 --> 00:30:51,876 Speaker 2: they need in their pants, so if they go down, 524 00:30:52,356 --> 00:30:56,276 Speaker 2: a medic can come up, take it out, and you know, 525 00:30:56,396 --> 00:30:59,916 Speaker 2: put it, you know, start resustinating somebody. It will be 526 00:31:00,356 --> 00:31:04,116 Speaker 2: in every ambulance so that if somebody goes to the 527 00:31:04,156 --> 00:31:07,076 Speaker 2: scene of an accident somebody's bleeding, they'll be able to 528 00:31:07,076 --> 00:31:09,236 Speaker 2: give them blood right away, just like they can of 529 00:31:09,316 --> 00:31:15,116 Speaker 2: oxygen or CPR. It will be stored in depots for 530 00:31:15,236 --> 00:31:19,356 Speaker 2: mass casualty incidents. So many people don't know at the say, 531 00:31:19,356 --> 00:31:22,756 Speaker 2: for example, at the Boston Marathon bombing, they actually were 532 00:31:22,836 --> 00:31:27,916 Speaker 2: running out of blood there, and unfortunately those incidents haven't stopped. 533 00:31:28,396 --> 00:31:33,196 Speaker 2: So there will be depots around the country where there's 534 00:31:33,556 --> 00:31:37,876 Speaker 2: warehouse shell stable blood. It will be on cruise ships. 535 00:31:38,076 --> 00:31:41,676 Speaker 2: It will be in resource limited countries like sub Saharan Africa. 536 00:31:41,836 --> 00:31:43,996 Speaker 2: It will be on the space station. It will be 537 00:31:44,076 --> 00:31:48,156 Speaker 2: on the mission to Mars. It will be wherever it's 538 00:31:48,276 --> 00:31:53,356 Speaker 2: hard to get blood. We'll be back in a minute 539 00:31:53,476 --> 00:31:54,356 Speaker 2: with the lightning round. 540 00:32:05,196 --> 00:32:08,996 Speaker 1: Okay, lightning round. What's your second favorite type of blood cell? 541 00:32:09,676 --> 00:32:13,676 Speaker 1: Nice as opposed to red blood I'm assuming I'm presuming 542 00:32:13,716 --> 00:32:16,836 Speaker 1: that red blood cells are your favorite, right, Yeah, the 543 00:32:17,556 --> 00:32:20,356 Speaker 1: juvenile red blood cells, the red cell, the cells that 544 00:32:20,476 --> 00:32:23,916 Speaker 1: make red blood cells. Okay, third favorite, third favorite? Yeah, sorry, 545 00:32:24,436 --> 00:32:27,316 Speaker 1: well i'd say platelets are pretty important and they're far 546 00:32:27,396 --> 00:32:31,116 Speaker 1: more complicated than red blood cells. But no platelets and 547 00:32:31,636 --> 00:32:35,356 Speaker 1: we just bleed to death. So plate is very important 548 00:32:35,356 --> 00:32:39,236 Speaker 1: and fascinating the whole. Like clotting cascade things seems wild, 549 00:32:39,276 --> 00:32:40,956 Speaker 1: right because you want the blood to clot when it 550 00:32:40,996 --> 00:32:43,396 Speaker 1: needs to clot, but you really don't want it to 551 00:32:43,436 --> 00:32:46,076 Speaker 1: clot when it's not supposed to clot, right, Like, that's 552 00:32:46,116 --> 00:32:49,156 Speaker 1: such a high stakes equilibrium. 553 00:32:49,316 --> 00:32:52,356 Speaker 2: It's an amazing system and amazing that it works when 554 00:32:52,396 --> 00:32:57,036 Speaker 2: it does. But yes, clotting system is incredible and very 555 00:32:57,236 --> 00:32:58,196 Speaker 2: very complicated. 556 00:32:58,996 --> 00:33:01,436 Speaker 1: What's one thing you wish we understood about blood that 557 00:33:01,556 --> 00:33:05,436 Speaker 1: is still a mystery why we have to keep remaking it? 558 00:33:05,516 --> 00:33:08,396 Speaker 2: So the you know, we have to renew red blood 559 00:33:08,396 --> 00:33:13,076 Speaker 2: cells every three months. They don't last very long. We 560 00:33:13,156 --> 00:33:16,716 Speaker 2: live with the neurons that we started with as a baby, 561 00:33:17,396 --> 00:33:20,956 Speaker 2: but the red cells you had in the spring, they're 562 00:33:20,996 --> 00:33:24,196 Speaker 2: all gone, Every last one of them is gone. So 563 00:33:24,236 --> 00:33:27,316 Speaker 2: you turn over all of your red blood cells. And 564 00:33:27,356 --> 00:33:32,116 Speaker 2: it's incredible that we actually do that because it's a 565 00:33:32,196 --> 00:33:35,996 Speaker 2: huge part of our quote budget in terms of energy 566 00:33:36,036 --> 00:33:36,916 Speaker 2: and nutrition. 567 00:33:37,276 --> 00:33:39,756 Speaker 1: It would be a huge evolutionary advantage in a world 568 00:33:39,756 --> 00:33:42,996 Speaker 1: of scarce food, presumably, so there must be some reason 569 00:33:43,236 --> 00:33:45,916 Speaker 1: that it doesn't work, right, Yeah, but we don't know. 570 00:33:46,596 --> 00:33:52,076 Speaker 1: What's one common misconception that lay people have about blood 571 00:33:53,036 --> 00:33:57,636 Speaker 1: that it's not alive. It's as alive as your brain. 572 00:33:58,956 --> 00:34:01,836 Speaker 1: People forget your blood is a living tissue. 573 00:34:01,916 --> 00:34:06,596 Speaker 2: Is just a liquid organ, and it's alive, and it's 574 00:34:06,636 --> 00:34:08,116 Speaker 2: constantly doing things. 575 00:34:08,156 --> 00:34:10,276 Speaker 1: It's very very sensitive. 576 00:34:10,516 --> 00:34:14,956 Speaker 2: It responds perfectly to you know, when you need to 577 00:34:15,476 --> 00:34:19,516 Speaker 2: increase oxygen delivery or reduce it. It can clot, it 578 00:34:19,596 --> 00:34:23,236 Speaker 2: can fight infection. It has a lot of functions. And 579 00:34:23,276 --> 00:34:26,676 Speaker 2: people just think, well, it's just you know, like motor oil. 580 00:34:27,316 --> 00:34:30,916 Speaker 2: But it's it's very sophisticated. 581 00:34:32,156 --> 00:34:39,636 Speaker 1: What's your view on nominative determinism? Nominative determinatism? So are 582 00:34:39,676 --> 00:34:42,996 Speaker 1: we what we call ourselves? Is that? Yes, I'm frankly 583 00:34:43,036 --> 00:34:44,836 Speaker 1: surprised that you have not heard that phrase. I'll be 584 00:34:44,836 --> 00:34:45,676 Speaker 1: honest with you. Yeah. 585 00:34:45,996 --> 00:34:49,196 Speaker 2: So my last name, so, I fought it for a 586 00:34:49,236 --> 00:34:52,636 Speaker 2: long time. In fact, wanted to become a marine biologist. 587 00:34:52,796 --> 00:34:55,836 Speaker 1: I Jacques Cousteau was my idol when I was growing up, 588 00:34:55,876 --> 00:35:01,116 Speaker 1: and but you know, I succumbed and went to medical school. 589 00:35:01,156 --> 00:35:11,196 Speaker 1: I'm actually quite happy that I did. Doctor Alan Doctor 590 00:35:11,556 --> 00:35:14,956 Speaker 1: is a professor of pediatrics and bioengineering at the University 591 00:35:14,956 --> 00:35:18,316 Speaker 1: of Maryland and he's the co founder and chief scientific 592 00:35:18,356 --> 00:35:23,676 Speaker 1: officer of Kalosite. Please email us at problem at pushkin 593 00:35:23,836 --> 00:35:26,676 Speaker 1: dot fm. We are always looking for new guests for 594 00:35:26,796 --> 00:35:31,116 Speaker 1: the show. Today's show was produced by Trinomanino and Gabriel 595 00:35:31,156 --> 00:35:35,356 Speaker 1: Hunter Chang. It was edited by Alexander Garretson and engineered 596 00:35:35,356 --> 00:35:38,156 Speaker 1: by Sarah Brugueir. I'm Jacob Goldstein and we'll be back 597 00:35:38,196 --> 00:35:54,196 Speaker 1: next week with another episode of What's Your Problem.