1 00:00:15,356 --> 00:00:22,716 Speaker 1: Pushkin. One subject we've discussed from time to time on 2 00:00:22,796 --> 00:00:27,916 Speaker 1: this show is space outer space for obvious reasons, you know, 3 00:00:28,116 --> 00:00:32,316 Speaker 1: Final Frontier, etc. Another subject we've done a bunch of 4 00:00:32,356 --> 00:00:37,396 Speaker 1: episodes about drug research, figuring out new and better ways 5 00:00:37,436 --> 00:00:41,596 Speaker 1: to make new medicines. Also for obvious reasons, it's high 6 00:00:41,676 --> 00:00:46,916 Speaker 1: stakes life or death innovation. Today we're combining those two subjects. 7 00:00:47,276 --> 00:00:57,076 Speaker 1: It's a show about drug research in space. I'm Jacob 8 00:00:57,116 --> 00:00:59,316 Speaker 1: Goldstein and this is What's Your Problem, the show where 9 00:00:59,356 --> 00:01:02,436 Speaker 1: I talk to people who are trying to make technological progress. 10 00:01:02,996 --> 00:01:06,036 Speaker 1: My guest today is Paul Reiker. He's a research scientist 11 00:01:06,076 --> 00:01:09,476 Speaker 1: at the drug company Merk. Paul's problem is this, how 12 00:01:09,476 --> 00:01:12,876 Speaker 1: can you run experiments in space to make better drugs 13 00:01:12,916 --> 00:01:15,756 Speaker 1: on Earth. To be clear, Paul has not gone to 14 00:01:15,796 --> 00:01:19,076 Speaker 1: space himself, but over the past thirty or so years, 15 00:01:19,156 --> 00:01:22,076 Speaker 1: he has sent tubes full of proteins and drugs up 16 00:01:22,156 --> 00:01:25,556 Speaker 1: to space, first on the Space Shuttle and more recently 17 00:01:25,636 --> 00:01:29,276 Speaker 1: on rockets to the International Space Station, and he's instructed 18 00:01:29,316 --> 00:01:32,556 Speaker 1: astronauts on how to carry out dozens of experiments in space. 19 00:01:33,636 --> 00:01:35,916 Speaker 1: One of Paul's more recent experiments looked at a common 20 00:01:35,916 --> 00:01:40,836 Speaker 1: type of drug called monoclonal antibodies. Monoclonal antibodies are used 21 00:01:40,836 --> 00:01:44,436 Speaker 1: to treat cancer, among other diseases, and they're currently very 22 00:01:44,556 --> 00:01:48,316 Speaker 1: time consuming and very expensive to deliver, and what Paul 23 00:01:48,396 --> 00:01:51,796 Speaker 1: was trying to figure out was a cheaper, faster way 24 00:01:51,796 --> 00:01:55,476 Speaker 1: to deliver those drugs. We'll talk about that experiment later 25 00:01:55,476 --> 00:02:01,476 Speaker 1: in the show. Paul specializes in crystallization, basically getting molecules 26 00:02:01,476 --> 00:02:05,076 Speaker 1: to form crystal structures, and crystallization is important in the 27 00:02:05,156 --> 00:02:07,916 Speaker 1: drug business in a few ways. For one thing, it's 28 00:02:07,956 --> 00:02:11,836 Speaker 1: really important for study the molecules that drugs target, and 29 00:02:11,996 --> 00:02:14,996 Speaker 1: for another, crystallization plays an important role in the process 30 00:02:15,036 --> 00:02:18,516 Speaker 1: of manufacturing drugs. So to start, I asked Paul, what 31 00:02:18,596 --> 00:02:22,556 Speaker 1: are the reasons for going to space to do crystallization experiments? 32 00:02:23,076 --> 00:02:27,996 Speaker 2: Okay, one is the obvious. One is sedimentation. We all 33 00:02:28,036 --> 00:02:32,276 Speaker 2: see astronauts floating in space. So when you go grow 34 00:02:32,356 --> 00:02:37,196 Speaker 2: crystals in space, they too remain suspended in space as 35 00:02:37,236 --> 00:02:42,036 Speaker 2: they grow, and this suspended particle then has an opportunity 36 00:02:42,116 --> 00:02:46,316 Speaker 2: then to grow more perfect than it would if it 37 00:02:46,396 --> 00:02:51,076 Speaker 2: was sedimenting, dropping in the solution as it was being formed. 38 00:02:51,916 --> 00:02:53,836 Speaker 1: So on Earth, when you're trying to do this you 39 00:02:53,916 --> 00:02:57,116 Speaker 1: have this problem, which is the particles sync to the 40 00:02:57,116 --> 00:03:00,756 Speaker 1: bottom like whatever correct coffee grounds in a cup or something. 41 00:03:00,796 --> 00:03:03,156 Speaker 1: But when you're in space, you don't have that problem 42 00:03:03,196 --> 00:03:05,436 Speaker 1: because there is no sinking and there is no ground. 43 00:03:05,676 --> 00:03:09,476 Speaker 2: Right. And the second property we'd like to take advantage 44 00:03:09,516 --> 00:03:14,956 Speaker 2: of is that molecules move more slowly in space. So 45 00:03:15,436 --> 00:03:21,996 Speaker 2: processes that involve adding molecules to say, like a crystal, 46 00:03:22,916 --> 00:03:26,876 Speaker 2: the molecules have a chance then to be discriminate to 47 00:03:26,876 --> 00:03:32,036 Speaker 2: get the best molecule fit within the crystal lattice. 48 00:03:32,236 --> 00:03:35,956 Speaker 1: So okay, so now we know why space is a 49 00:03:35,996 --> 00:03:39,916 Speaker 1: good place to really you're trying to form crystals fundamentally, right, 50 00:03:39,916 --> 00:03:44,316 Speaker 1: it's a good place to cause molecules to crystallize for 51 00:03:44,396 --> 00:03:48,476 Speaker 1: the reasons you articulated. I don't want to do all 52 00:03:48,556 --> 00:03:51,556 Speaker 1: thirty years of your working on crystals in space, but 53 00:03:51,636 --> 00:03:54,076 Speaker 1: I wonder if there's like a moment from the kind 54 00:03:54,116 --> 00:03:58,196 Speaker 1: of early Space Shuttle era, like what was one kind 55 00:03:58,236 --> 00:04:01,996 Speaker 1: of important early finding you had from your work on 56 00:04:02,036 --> 00:04:02,756 Speaker 1: the Space Shuttle. 57 00:04:03,836 --> 00:04:10,156 Speaker 2: I have a interesting but very sad story to say 58 00:04:10,196 --> 00:04:15,276 Speaker 2: about that. One of the last flights we'd Space Shuttle 59 00:04:15,316 --> 00:04:19,796 Speaker 2: flights that we did was STS one o seven. That 60 00:04:19,956 --> 00:04:24,596 Speaker 2: Space Transportation System one O seven and that was Columbia 61 00:04:26,076 --> 00:04:31,316 Speaker 2: went up in January two thousand and three, and we 62 00:04:31,316 --> 00:04:36,956 Speaker 2: were trying to grow large crystals suitable for structural studies, 63 00:04:38,396 --> 00:04:42,876 Speaker 2: and I uniquely had the opportunity since one of the 64 00:04:42,916 --> 00:04:47,676 Speaker 2: people in our team was retiring, so we got to 65 00:04:47,676 --> 00:04:54,196 Speaker 2: go to the to the launch site of Columbia. The 66 00:04:54,316 --> 00:04:58,236 Speaker 2: night before launch, we went one hundred and thirty feet 67 00:04:58,356 --> 00:05:01,476 Speaker 2: up in the air onto a scaffolding, up into the 68 00:05:01,516 --> 00:05:05,196 Speaker 2: top of where the nose of the shuttle was, and 69 00:05:05,236 --> 00:05:10,676 Speaker 2: it was it was cold, freezing cold. Little did we 70 00:05:10,756 --> 00:05:15,956 Speaker 2: know but the next day, upon launch, a frozen chunk 71 00:05:16,236 --> 00:05:21,116 Speaker 2: of that solid rocket booster would fall and hit the 72 00:05:21,156 --> 00:05:26,556 Speaker 2: wing of Space Shuttle Columbia, and that, upon re entry 73 00:05:26,876 --> 00:05:33,796 Speaker 2: two weeks later, would cause the breakup of Columbia over Texas. 74 00:05:33,956 --> 00:05:38,596 Speaker 2: There was a debris field over sixty three miles for that. 75 00:05:39,356 --> 00:05:41,716 Speaker 1: And the death of the astronauts right, just yes. 76 00:05:42,116 --> 00:05:45,996 Speaker 2: So NATS at that point decided that they would focus 77 00:05:46,156 --> 00:05:51,796 Speaker 2: on doing building the International Space Station and no longer 78 00:05:52,476 --> 00:05:59,236 Speaker 2: spend time with secondary projects like this. About three four 79 00:05:59,276 --> 00:06:05,876 Speaker 2: months after this disaster, I got a call from NASA 80 00:06:05,956 --> 00:06:09,956 Speaker 2: and said we found some of your bottle. I flew 81 00:06:10,196 --> 00:06:14,636 Speaker 2: one hundred small one mL bottles and they said, we 82 00:06:14,716 --> 00:06:16,516 Speaker 2: found a few of them. Would you like to come 83 00:06:16,556 --> 00:06:19,716 Speaker 2: down and take a look at them? So I said yes, 84 00:06:20,196 --> 00:06:25,836 Speaker 2: So I go down to the shuttle reconstruction site. They 85 00:06:25,836 --> 00:06:31,316 Speaker 2: had this dedicated site there and I found three vials 86 00:06:31,356 --> 00:06:38,916 Speaker 2: and within those three bottles there were crystals, and those 87 00:06:38,996 --> 00:06:44,396 Speaker 2: crystals when we did the X ray diffraction study, diffracted 88 00:06:44,436 --> 00:06:48,156 Speaker 2: better than any crystals we had ever seen before. So 89 00:06:48,596 --> 00:06:53,916 Speaker 2: one of my great honors in my life was about 90 00:06:53,916 --> 00:06:56,596 Speaker 2: three months after that, NASA asked me, would you be 91 00:06:56,636 --> 00:07:01,396 Speaker 2: willing to talk to the families of the astronauts and 92 00:07:01,516 --> 00:07:05,476 Speaker 2: tell them about the results of your experiment. So it 93 00:07:05,516 --> 00:07:09,596 Speaker 2: was a great honor for me to have this opertunity 94 00:07:10,596 --> 00:07:20,076 Speaker 2: to hopefully give some consolation to the to the families 95 00:07:21,196 --> 00:07:23,996 Speaker 2: about you know, we did get some science from this 96 00:07:24,716 --> 00:07:27,876 Speaker 2: and give them some relief in their suffering. 97 00:07:30,276 --> 00:07:35,876 Speaker 1: And what are the practical implications of having crystals that 98 00:07:35,956 --> 00:07:38,476 Speaker 1: diffract really well? Why is that meaningful? 99 00:07:39,676 --> 00:07:43,836 Speaker 2: It allows you to see the intimate contacts that are 100 00:07:43,876 --> 00:07:51,436 Speaker 2: made within the protein to design the better small molecule 101 00:07:51,516 --> 00:07:55,276 Speaker 2: drugs that are in complex with those proteins. So one 102 00:07:55,316 --> 00:07:58,436 Speaker 2: of the interesting things was is that the crystals that 103 00:07:58,916 --> 00:08:05,356 Speaker 2: grew from that experiment was from an impure sample. We're 104 00:08:05,396 --> 00:08:09,556 Speaker 2: actually looking at it for purification, and one of the 105 00:08:09,596 --> 00:08:14,396 Speaker 2: impurities in there was zinc. And basically found that the 106 00:08:14,436 --> 00:08:18,076 Speaker 2: reason why the crystals diffracted so much better than what 107 00:08:18,156 --> 00:08:21,596 Speaker 2: we had previously seen before is because there was a 108 00:08:21,716 --> 00:08:27,596 Speaker 2: zinc in between two molecules of interferon stabilizing it, allowing 109 00:08:27,636 --> 00:08:31,076 Speaker 2: it to have a really stable form. So that was 110 00:08:31,156 --> 00:08:34,236 Speaker 2: something that was I have to say that, you know 111 00:08:34,396 --> 00:08:39,556 Speaker 2: a lot of microgravity research, you're really at the basic level, 112 00:08:40,436 --> 00:08:44,196 Speaker 2: and you gives you an opportunity to really change the 113 00:08:44,236 --> 00:08:49,956 Speaker 2: way you think because you're so focused on, you know, 114 00:08:51,196 --> 00:08:53,916 Speaker 2: very simple steps in that process. 115 00:08:54,236 --> 00:08:56,956 Speaker 1: You could see the protein more clearly than anyone had 116 00:08:56,996 --> 00:08:57,956 Speaker 1: ever seen it before. 117 00:08:58,316 --> 00:09:01,156 Speaker 2: Absolutely, So that was the key finding. 118 00:09:01,796 --> 00:09:04,356 Speaker 1: So okay, so we get so we get, you know, 119 00:09:04,476 --> 00:09:08,956 Speaker 1: now into well into the twenty first century here and 120 00:09:09,116 --> 00:09:12,996 Speaker 1: there's this new class of drugs, monoclonal antibodies, that are 121 00:09:13,116 --> 00:09:16,596 Speaker 1: very powerful drugs, but they're very hard to deliver, right, 122 00:09:16,636 --> 00:09:18,716 Speaker 1: and this is a problem you're working on solving. So 123 00:09:18,796 --> 00:09:23,396 Speaker 1: tell me about the problem with delivering monoclonal antibodies. 124 00:09:23,796 --> 00:09:28,076 Speaker 2: Okay. The issue is is that still to this day, 125 00:09:29,076 --> 00:09:35,716 Speaker 2: most monoclone antibody therapeutics, which are given for a range 126 00:09:35,756 --> 00:09:44,036 Speaker 2: of different modalities from cancer to cardiovascular disease to effective diseases. 127 00:09:44,996 --> 00:09:53,156 Speaker 2: They've really revolutionized the way pharmaceutical research has been going on. Okay, 128 00:09:53,636 --> 00:09:58,036 Speaker 2: so they are very good drugs. However, in the case 129 00:09:58,236 --> 00:10:04,636 Speaker 2: of oncology patients especially, they have to get an infusion 130 00:10:04,996 --> 00:10:09,716 Speaker 2: every three weeks and this is usually in the hospital setting. 131 00:10:10,556 --> 00:10:13,316 Speaker 2: So this is an all day affair not only for 132 00:10:13,436 --> 00:10:18,116 Speaker 2: the patient, but usually a caregiver that's accompanying their patient 133 00:10:18,156 --> 00:10:21,276 Speaker 2: who's taking time off from work to go for these 134 00:10:21,316 --> 00:10:29,636 Speaker 2: effusions every three weeks and usually a therapy could go 135 00:10:29,676 --> 00:10:32,596 Speaker 2: as long as six months to a year. So this 136 00:10:32,756 --> 00:10:36,676 Speaker 2: is a tremendous impact on both the patient and the 137 00:10:36,796 --> 00:10:38,556 Speaker 2: caregiver and it adds. 138 00:10:38,316 --> 00:10:41,916 Speaker 1: To the expense right, non trivially. It's more expensive just 139 00:10:41,956 --> 00:10:44,076 Speaker 1: because it takes more labor on the side of the 140 00:10:44,116 --> 00:10:48,676 Speaker 1: hospital or the infusion center. It's a complicated, expensive, time 141 00:10:48,716 --> 00:10:49,676 Speaker 1: consuming process. 142 00:10:49,956 --> 00:10:53,476 Speaker 2: It's about half the cost of the delivery of the drug. 143 00:10:54,356 --> 00:10:59,556 Speaker 2: Is this infusion all right, So we are looking at 144 00:10:59,596 --> 00:11:06,756 Speaker 2: opportunities to make crystalline suspensions So one of the let 145 00:11:06,836 --> 00:11:08,596 Speaker 2: me take a step back and say one of the 146 00:11:08,716 --> 00:11:12,196 Speaker 2: issues with making well, why don't you just make a 147 00:11:12,316 --> 00:11:18,596 Speaker 2: high concentrated liquid formulation that you can inject? 148 00:11:19,716 --> 00:11:22,156 Speaker 1: So the issue is to be clear, Just make it 149 00:11:22,156 --> 00:11:24,436 Speaker 1: be a shot, like getting a flu shot or something 150 00:11:24,476 --> 00:11:25,236 Speaker 1: fast and easy. 151 00:11:25,396 --> 00:11:29,676 Speaker 2: Right. So the problem is that in the liquid form okay, 152 00:11:30,076 --> 00:11:35,236 Speaker 2: as you increase the concentration, it becomes thick and more 153 00:11:35,316 --> 00:11:42,196 Speaker 2: difficult to inject. So I don't think most people would 154 00:11:42,276 --> 00:11:45,876 Speaker 2: enjoy getting an injection that may take five to ten 155 00:11:45,956 --> 00:11:48,996 Speaker 2: minutes of time in order to get the same dose 156 00:11:49,116 --> 00:11:53,236 Speaker 2: as you would in infusion. It would be extremely painful. 157 00:11:53,676 --> 00:11:59,116 Speaker 2: Patients would not accept that kind of a delivery system 158 00:11:59,276 --> 00:12:03,356 Speaker 2: of pain pain over a long period of time. Let 159 00:12:03,436 --> 00:12:07,236 Speaker 2: me put this way. So we decided to look at 160 00:12:07,556 --> 00:12:15,756 Speaker 2: there was some evidence that high concentrated crystalline suspensions are 161 00:12:16,116 --> 00:12:22,116 Speaker 2: lower in viscosity than the comparable liquid formulations. Okay, So 162 00:12:23,036 --> 00:12:28,316 Speaker 2: we went about looking see if we could crystallize monoclonal antibodies, 163 00:12:29,636 --> 00:12:34,716 Speaker 2: and we had success with one monol anti monoclony antibody, 164 00:12:35,276 --> 00:12:41,396 Speaker 2: and ultimately we hit discovered conditions for crystallizing pambrolasm app, 165 00:12:42,036 --> 00:12:49,516 Speaker 2: which is a active pharmaceutical ingredient for one of our oncology. 166 00:12:48,956 --> 00:12:54,996 Speaker 1: Drugs, and so you're studying it on Earth right, trying 167 00:12:55,036 --> 00:12:57,236 Speaker 1: to understand if you can get it into a crystal 168 00:12:57,236 --> 00:13:00,796 Speaker 1: structure so that so that it could be given as 169 00:13:00,796 --> 00:13:05,236 Speaker 1: a quick injection rather than as a long infusion. What's like? 170 00:13:06,236 --> 00:13:09,796 Speaker 1: What's why? Like, you're going to go to space. Spoil 171 00:13:09,876 --> 00:13:11,396 Speaker 1: the story. You're going to go to space. You're going 172 00:13:11,436 --> 00:13:13,556 Speaker 1: to send something up to space to study, But why 173 00:13:13,876 --> 00:13:16,116 Speaker 1: did you try and do it on Earth first? And 174 00:13:16,156 --> 00:13:16,796 Speaker 1: did it work? 175 00:13:16,996 --> 00:13:21,396 Speaker 2: Absolutely? It works? The question is can you make it better? 176 00:13:21,796 --> 00:13:25,996 Speaker 2: We always like to come up with the best therapeutic 177 00:13:26,156 --> 00:13:31,276 Speaker 2: that we can deliver that has, you know, the stability 178 00:13:31,596 --> 00:13:37,196 Speaker 2: and properties that we're looking for in a final product. 179 00:13:38,076 --> 00:13:41,276 Speaker 2: And then second to that, we're always looking at opportunities 180 00:13:41,316 --> 00:13:47,956 Speaker 2: to improve the manufacture of our drugs, possibly reduce cost 181 00:13:49,436 --> 00:13:53,996 Speaker 2: and then have a more stable formulation. For example, one 182 00:13:54,036 --> 00:13:57,836 Speaker 2: of our goals would be to show that the a 183 00:13:57,956 --> 00:14:03,316 Speaker 2: crystalline suspension, since it's inherently more stable. Does that allow 184 00:14:03,396 --> 00:14:08,756 Speaker 2: you to take a monocle antibody drug that is stored 185 00:14:09,316 --> 00:14:13,556 Speaker 2: in a refrigerator to now be allowed to be stable 186 00:14:13,756 --> 00:14:18,116 Speaker 2: save for six months at room temperature, and therefore that 187 00:14:18,236 --> 00:14:22,556 Speaker 2: has a big impact on the number of patients globally 188 00:14:23,076 --> 00:14:23,996 Speaker 2: that can treat. 189 00:14:24,116 --> 00:14:25,956 Speaker 1: So then if it could be a shot that is 190 00:14:25,956 --> 00:14:28,476 Speaker 1: stable at room temperature, then that opens up a lot 191 00:14:28,516 --> 00:14:30,996 Speaker 1: of the developing world that right now is frankly just 192 00:14:31,036 --> 00:14:36,556 Speaker 1: doesn't have the infrastructure to deliver refrigerated infusion drugs. 193 00:14:36,596 --> 00:14:36,996 Speaker 2: Correct. 194 00:14:37,476 --> 00:14:39,836 Speaker 1: Do you just call up NASA and say, hey, NASA, 195 00:14:39,916 --> 00:14:42,116 Speaker 1: it's me, I want to send something to the space station. 196 00:14:42,476 --> 00:14:45,476 Speaker 2: No, that's not how it works. So let me take 197 00:14:45,516 --> 00:14:48,836 Speaker 2: a step back and say that after the Space Shuttle 198 00:14:49,356 --> 00:14:56,516 Speaker 2: Columbia broke apart over Texas, there was no microgravity research 199 00:14:56,916 --> 00:15:02,956 Speaker 2: actively research going on to about twenty ten, two eleven, 200 00:15:03,676 --> 00:15:08,636 Speaker 2: and the US Congress said, we built this station, we 201 00:15:08,716 --> 00:15:12,236 Speaker 2: have this beautiful laboratory in space, and it's being underutilized. 202 00:15:12,836 --> 00:15:18,356 Speaker 2: So they set up a nonprofit called the Center for 203 00:15:18,396 --> 00:15:22,796 Speaker 2: the Advancement of Science in Space and allowed them to 204 00:15:22,916 --> 00:15:28,756 Speaker 2: manage science on the International Space Station. So about twenty 205 00:15:28,836 --> 00:15:35,316 Speaker 2: eleven twenty twelve, somebody from CASES reached out to me 206 00:15:35,396 --> 00:15:40,396 Speaker 2: and said, would you be interested in doing some microgravity research? 207 00:15:40,836 --> 00:15:42,596 Speaker 2: Come up with a proposal. 208 00:15:42,876 --> 00:15:45,276 Speaker 1: That's a nice call to get yes, And so you 209 00:15:45,396 --> 00:15:50,716 Speaker 1: proposed this crystallization research on a monoclonal atta body and 210 00:15:50,756 --> 00:15:53,556 Speaker 1: they say yes, and what happens? 211 00:15:54,196 --> 00:15:57,716 Speaker 2: All right, So we were at this time was the 212 00:15:57,756 --> 00:16:03,316 Speaker 2: early stages of where SpaceX, the Falcon nine rockets were 213 00:16:03,516 --> 00:16:11,516 Speaker 2: starting to deliver their Dragon module to resupply missions to 214 00:16:11,636 --> 00:16:19,276 Speaker 2: the International Space Station, and we got manifested in twenty 215 00:16:19,356 --> 00:16:23,796 Speaker 2: fourteen to crystallize a monoclone at a body. 216 00:16:24,956 --> 00:16:27,516 Speaker 1: Manifested in this context, it's not some new age tournament. 217 00:16:27,556 --> 00:16:29,516 Speaker 1: Means you got put on the list of stuff that 218 00:16:29,596 --> 00:16:30,436 Speaker 1: gets to go up there. 219 00:16:30,676 --> 00:16:33,316 Speaker 2: Yes, that's what it means. You know. It was basically 220 00:16:37,596 --> 00:16:39,996 Speaker 2: these are all the you know NASA terms. You know 221 00:16:40,076 --> 00:16:45,116 Speaker 2: you're manifested, you know. So we always do the same 222 00:16:45,196 --> 00:16:48,076 Speaker 2: experiment on ground that we do in space. 223 00:16:48,316 --> 00:16:51,036 Speaker 1: Altimatically as a control control. 224 00:16:51,316 --> 00:16:53,916 Speaker 2: And not only that, we usually do it in triplicate 225 00:16:55,116 --> 00:16:57,956 Speaker 2: to ensure that, you know, it's not a one off 226 00:16:58,116 --> 00:17:00,596 Speaker 2: or something that's not you know what I mean. 227 00:17:01,516 --> 00:17:02,836 Speaker 1: I mean, if you're sending one of them all the 228 00:17:02,876 --> 00:17:04,636 Speaker 1: way to space, you might as well do three on hearth. 229 00:17:04,916 --> 00:17:07,596 Speaker 2: We do we well, we do three in space too. 230 00:17:07,996 --> 00:17:11,956 Speaker 1: Oh interesting, so that it's not in of one. 231 00:17:11,716 --> 00:17:15,676 Speaker 2: One at least you can show reproducibility that this is 232 00:17:15,716 --> 00:17:18,596 Speaker 2: a real uh you know, find that you have. 233 00:17:18,796 --> 00:17:21,956 Speaker 1: And so so it goes up on a Falcon nine rocket, 234 00:17:22,036 --> 00:17:24,956 Speaker 1: it gets to the space station. Are you involved as 235 00:17:24,996 --> 00:17:27,876 Speaker 1: it's happening, Are you like talking to the astronauts on 236 00:17:27,916 --> 00:17:28,476 Speaker 1: the phone? 237 00:17:28,996 --> 00:17:33,476 Speaker 2: I am. That's a good question. Usually there's there's a 238 00:17:33,636 --> 00:17:39,516 Speaker 2: NASA person that's talking directly to the astronauts while they're 239 00:17:39,756 --> 00:17:45,556 Speaker 2: activating our experiment. And I can actually watch by video 240 00:17:46,396 --> 00:17:51,636 Speaker 2: and I can send messages through cases through NASA, uh, 241 00:17:51,716 --> 00:17:54,516 Speaker 2: you know, to you know, if I see anything that's so. 242 00:17:54,476 --> 00:17:57,356 Speaker 1: You're like texting the astronaut they're like wait, wait, no, 243 00:17:57,436 --> 00:17:59,396 Speaker 1: turn it the other way or what like, what is 244 00:17:59,436 --> 00:17:59,876 Speaker 1: going on? 245 00:18:00,836 --> 00:18:04,316 Speaker 2: That's a that's a very good point we give. They 246 00:18:04,356 --> 00:18:09,396 Speaker 2: have iPads that they use and there's very detail held 247 00:18:09,476 --> 00:18:14,436 Speaker 2: instructions of the of the process that they're doing while 248 00:18:14,476 --> 00:18:17,036 Speaker 2: doing these experiments. You've got to keep in mind that 249 00:18:17,116 --> 00:18:20,476 Speaker 2: they're doing hundreds of experiments, you know. 250 00:18:20,716 --> 00:18:24,796 Speaker 1: So they're astronauts on the space station. Presumably they're busy, right. 251 00:18:24,876 --> 00:18:28,036 Speaker 2: They're they're very busy, and and you know, one of 252 00:18:28,076 --> 00:18:31,156 Speaker 2: the things that's always impressed me is the is the 253 00:18:31,236 --> 00:18:38,476 Speaker 2: fact that they're they're very uh focused, calm individuals. 254 00:18:38,636 --> 00:18:40,836 Speaker 1: I feel like that's what you'd really want to optimize 255 00:18:40,876 --> 00:18:44,436 Speaker 1: for in selecting an astronaut. Right focused is what I 256 00:18:44,476 --> 00:18:46,636 Speaker 1: would hire for if I was hiring an astronaut. 257 00:18:46,876 --> 00:18:51,516 Speaker 2: And they're curious too. They they they see their unique 258 00:18:51,916 --> 00:18:57,156 Speaker 2: opportunity to impact science, and you can tell that they're 259 00:18:57,236 --> 00:19:00,036 Speaker 2: enjoying what they're doing. You know, it's a I always 260 00:19:00,076 --> 00:19:06,316 Speaker 2: found them to be extremely interesting people, you know, inquisitive people. 261 00:19:09,636 --> 00:19:12,876 Speaker 1: In a minute, Paul's tubes come back from space and 262 00:19:12,916 --> 00:19:24,796 Speaker 1: he gets to look at his space crystals. That's Paul 263 00:19:24,956 --> 00:19:27,996 Speaker 1: how he gets the results of his experiments from space. 264 00:19:28,516 --> 00:19:30,916 Speaker 1: Like what happens after his crystals come back. 265 00:19:31,516 --> 00:19:36,996 Speaker 2: In the early days, the Dragon module would parachute down 266 00:19:37,116 --> 00:19:41,356 Speaker 2: in the Pacific Ocean off of California, and there would 267 00:19:41,396 --> 00:19:46,876 Speaker 2: be a tugboat that would go and would pluck that 268 00:19:47,436 --> 00:19:50,476 Speaker 2: Dragon module out of the ocean. It would be two 269 00:19:50,556 --> 00:19:55,116 Speaker 2: days back to the harbor and Long Beach and I 270 00:19:55,156 --> 00:19:59,196 Speaker 2: would go there. And I always thought it was hysterical 271 00:19:59,316 --> 00:20:02,836 Speaker 2: because if you were in Kennedy Space Center, there's so 272 00:20:03,036 --> 00:20:07,036 Speaker 2: much security you can't get near or anything. When this 273 00:20:07,236 --> 00:20:11,236 Speaker 2: boat gets to the dock, Long beach. They plucked this 274 00:20:11,316 --> 00:20:13,356 Speaker 2: thing out of the water, put it up on a 275 00:20:13,436 --> 00:20:16,836 Speaker 2: on a on a dock. They set up some folding 276 00:20:16,916 --> 00:20:20,596 Speaker 2: tables and said, here's your here's your experiment. 277 00:20:20,236 --> 00:20:23,996 Speaker 1: Here's your stuff. It's just like a yard sailor's stuff. 278 00:20:24,076 --> 00:20:29,156 Speaker 2: Like picking up fish at the dock and they hand 279 00:20:29,196 --> 00:20:31,716 Speaker 2: it over. And I would always be laughing hysterical as 280 00:20:31,756 --> 00:20:33,356 Speaker 2: they would do this. You know what I mean. 281 00:20:33,996 --> 00:20:36,516 Speaker 1: So you go, you walk up to the table, you say, 282 00:20:36,516 --> 00:20:39,036 Speaker 1: those are my tubes. They give you the tubes and 283 00:20:39,076 --> 00:20:41,596 Speaker 1: then what do you go look at them under a microscope? 284 00:20:41,676 --> 00:20:42,636 Speaker 1: Like what do you actually do? 285 00:20:43,196 --> 00:20:46,796 Speaker 2: We? We we take we take the experiments then and 286 00:20:46,916 --> 00:20:49,756 Speaker 2: believe it or not. In the early days, we would 287 00:20:49,796 --> 00:20:53,516 Speaker 2: just I was this was before that there was so 288 00:20:53,596 --> 00:20:59,316 Speaker 2: many regulations about flying. I would have a cooler that 289 00:20:59,436 --> 00:21:03,476 Speaker 2: I would keep and and carry the cooler back on 290 00:21:03,556 --> 00:21:07,556 Speaker 2: the flight back to New Jersey. Then to do analyze 291 00:21:07,596 --> 00:21:08,796 Speaker 2: the experiment. 292 00:21:08,716 --> 00:21:10,636 Speaker 1: Like I just think it's a cooler full of beer 293 00:21:10,716 --> 00:21:12,516 Speaker 1: or something, not your perfect crystals. 294 00:21:12,516 --> 00:21:13,556 Speaker 2: You can't do that now. 295 00:21:13,716 --> 00:21:16,076 Speaker 1: But by twenty sixteen, how are you doing it? On 296 00:21:16,116 --> 00:21:18,276 Speaker 1: this particular one? It was twenty sixteen, right, what do 297 00:21:18,316 --> 00:21:19,476 Speaker 1: you what do you'd actually. 298 00:21:19,276 --> 00:21:25,996 Speaker 2: Do twenty sixteen. We flew one hundred one mL bottles, 299 00:21:26,156 --> 00:21:29,116 Speaker 2: So these are all different connections conditions. 300 00:21:29,156 --> 00:21:33,356 Speaker 1: Looking at one millter's tiny one hundred tiny little little bottles. 301 00:21:34,956 --> 00:21:41,996 Speaker 2: And we get our experiment back and then we at 302 00:21:41,996 --> 00:21:46,796 Speaker 2: that point the dragon was parachuting down in the Gulf 303 00:21:46,836 --> 00:21:52,956 Speaker 2: of Mexico, and there's a helicopter that then picks up 304 00:21:53,596 --> 00:21:58,116 Speaker 2: the Dragon module brings it to Kennedy Space Center and 305 00:21:58,156 --> 00:22:02,196 Speaker 2: then within two hours I have the experiment. 306 00:22:02,476 --> 00:22:05,556 Speaker 1: And so what do you see that first look, this 307 00:22:05,636 --> 00:22:07,636 Speaker 1: thing's been up to space, it's been back. You look 308 00:22:07,676 --> 00:22:09,876 Speaker 1: at it. What do you see when you look at it? 309 00:22:10,476 --> 00:22:16,316 Speaker 2: Well, yeah, these crystals that are extremely small. Sure, so 310 00:22:17,116 --> 00:22:22,036 Speaker 2: it requires looking at the microscope, but since it's concentrated, 311 00:22:22,916 --> 00:22:27,436 Speaker 2: we can immediately tell that what we sent up was clear. 312 00:22:27,636 --> 00:22:32,396 Speaker 2: A clear liquid is now a paste, you know what 313 00:22:32,436 --> 00:22:35,036 Speaker 2: I mean, a white paste, and that looking at it 314 00:22:35,076 --> 00:22:37,396 Speaker 2: closely on the microscope, we could see that there were 315 00:22:37,436 --> 00:22:42,236 Speaker 2: crystals that were there. So what was what was unique 316 00:22:42,316 --> 00:22:47,276 Speaker 2: about the SpaceX ten experiment that we did with pen 317 00:22:47,396 --> 00:22:51,396 Speaker 2: roles am ab is. Remember the goal was to get large, big, 318 00:22:51,436 --> 00:22:56,036 Speaker 2: single crystals. Well, we had one group of experiments where 319 00:22:56,076 --> 00:22:59,316 Speaker 2: we got really really small crystals and a lot of them, 320 00:23:00,036 --> 00:23:04,636 Speaker 2: And I said, what's going on? So the ground experiment 321 00:23:04,716 --> 00:23:12,316 Speaker 2: comparable ground experiment had larger particles that were less homogeneous, 322 00:23:12,436 --> 00:23:18,276 Speaker 2: so the overall population was more broad whereas it's more heterogeneous. 323 00:23:18,276 --> 00:23:23,196 Speaker 2: It was correct. Yeah, okay, So we thought this would 324 00:23:23,196 --> 00:23:27,076 Speaker 2: be an excellent opportunity to look at these two types 325 00:23:27,316 --> 00:23:31,636 Speaker 2: of results and see whether it makes a difference. Are 326 00:23:31,676 --> 00:23:37,956 Speaker 2: they less viscous and do they show better injectability properties? 327 00:23:38,796 --> 00:23:42,836 Speaker 2: And what we found was is that the smaller particles 328 00:23:42,836 --> 00:23:49,956 Speaker 2: that more uniform gave lower viscosity better rejectability properties. 329 00:23:50,116 --> 00:23:51,836 Speaker 1: So that's what you want. 330 00:23:52,236 --> 00:23:54,436 Speaker 2: That's what we want, and it was not where we 331 00:23:54,476 --> 00:23:58,116 Speaker 2: were looking. We were we were up in the range 332 00:23:58,276 --> 00:24:02,316 Speaker 2: of particles that were like ten to thirty microns, and 333 00:24:02,356 --> 00:24:04,876 Speaker 2: then all of a sudden we had particles that were 334 00:24:04,916 --> 00:24:08,036 Speaker 2: really small and they showed this result. 335 00:24:08,516 --> 00:24:12,276 Speaker 1: So it's a prize. You didn't expect to get small 336 00:24:13,076 --> 00:24:14,556 Speaker 1: small particles. 337 00:24:14,236 --> 00:24:18,436 Speaker 2: Correct, right, huh. So what we did then once we 338 00:24:18,556 --> 00:24:24,036 Speaker 2: got that result was we came up with processes on 339 00:24:24,236 --> 00:24:31,436 Speaker 2: Earth that would mimic those results that we got in microgravity, 340 00:24:32,316 --> 00:24:35,356 Speaker 2: and then we were able to get a high density, 341 00:24:36,556 --> 00:24:39,476 Speaker 2: high yielding process from that. 342 00:24:39,796 --> 00:24:43,636 Speaker 1: Huh, So is is the hope then that that this 343 00:24:43,756 --> 00:24:49,036 Speaker 1: can lead to injectable versions not just of this particular 344 00:24:49,236 --> 00:24:54,036 Speaker 1: monoclonal antibody, but of monoclonal antibodies more generally. Absolutely, So 345 00:24:54,116 --> 00:24:55,796 Speaker 1: I want to talk about what you're working on next, 346 00:24:56,476 --> 00:24:58,956 Speaker 1: and I'm curious in particular about how you've been inspired 347 00:24:58,956 --> 00:25:00,876 Speaker 1: by an astronaut named Kate Robbins. 348 00:25:01,516 --> 00:25:08,396 Speaker 2: She was a molecular biologist from Stanford slash astronaut, and 349 00:25:08,716 --> 00:25:12,436 Speaker 2: I watch the video of her when she was in 350 00:25:12,516 --> 00:25:17,316 Speaker 2: a mission twenty sixteen where she said she can take 351 00:25:17,396 --> 00:25:21,556 Speaker 2: one personal item up to space. So she takes a 352 00:25:21,556 --> 00:25:26,356 Speaker 2: pipetta up to space and she just starts moving liquids 353 00:25:26,436 --> 00:25:29,956 Speaker 2: around the same way you do on Earth. And this 354 00:25:30,156 --> 00:25:34,036 Speaker 2: just blew me away because all of my experiments that 355 00:25:34,076 --> 00:25:39,756 Speaker 2: I had done before that were always in lock down hardware, 356 00:25:39,996 --> 00:25:42,676 Speaker 2: you know what I mean, with minimum conta. 357 00:25:42,916 --> 00:25:45,676 Speaker 1: Like, the idea that somebody could be pipetting in space, 358 00:25:45,716 --> 00:25:48,796 Speaker 1: to you as a sort of working scientist, is amazing. 359 00:25:48,916 --> 00:25:50,636 Speaker 1: Oh my god, if we could pipet up there, we 360 00:25:50,676 --> 00:25:51,436 Speaker 1: can do anything. 361 00:25:51,676 --> 00:25:56,356 Speaker 2: Absolutely, because up until that point we always felt as 362 00:25:56,396 --> 00:25:59,876 Speaker 2: though we had to take processes that we did on 363 00:25:59,996 --> 00:26:05,676 Speaker 2: Earth and then get them to Jerry rigged them to 364 00:26:05,676 --> 00:26:09,036 Speaker 2: get the work in microgravity hardware. So that was always 365 00:26:09,196 --> 00:26:14,356 Speaker 2: the issue. Okay. So when I saw you know, doctor 366 00:26:14,436 --> 00:26:19,756 Speaker 2: Kate Rubens start pipetting in space, it opened it. It 367 00:26:20,036 --> 00:26:22,276 Speaker 2: like blew me away. I was sitting in the audience 368 00:26:22,316 --> 00:26:23,996 Speaker 2: and I was looking around and said, did you just 369 00:26:24,156 --> 00:26:26,516 Speaker 2: see that? Did you just see what she was doing? 370 00:26:27,356 --> 00:26:29,356 Speaker 1: Because what what does it mean to you when you 371 00:26:29,356 --> 00:26:29,716 Speaker 1: see that? 372 00:26:29,756 --> 00:26:29,796 Speaker 2: What? 373 00:26:29,996 --> 00:26:31,876 Speaker 1: What? What do you think? What does it mean to you? 374 00:26:32,236 --> 00:26:34,516 Speaker 2: I mean what it says to me, and it may 375 00:26:34,636 --> 00:26:38,156 Speaker 2: sound strange, is that you can you can do the 376 00:26:38,196 --> 00:26:42,796 Speaker 2: same thing that Edison did one hundred years ago. So 377 00:26:42,836 --> 00:26:47,356 Speaker 2: you can you can have a laboratory or a base, okay, 378 00:26:47,916 --> 00:26:50,436 Speaker 2: and you can move liquids and you can play around 379 00:26:50,516 --> 00:26:53,996 Speaker 2: with different things, and it just opens up, you know, 380 00:26:54,316 --> 00:27:00,156 Speaker 2: a whole other world of opportunities for discovery, in innovation 381 00:27:00,876 --> 00:27:05,196 Speaker 2: in real time. So one pipett of revolution in one 382 00:27:05,196 --> 00:27:06,636 Speaker 2: pipet and one pipette. 383 00:27:06,956 --> 00:27:08,796 Speaker 1: So what do you want to do with this new 384 00:27:09,956 --> 00:27:11,476 Speaker 1: world of possibilities? 385 00:27:11,676 --> 00:27:16,796 Speaker 2: So what we did internally here is we came up 386 00:27:16,836 --> 00:27:22,516 Speaker 2: with our own three D printed hardware. Okay, so that 387 00:27:22,596 --> 00:27:27,156 Speaker 2: we could mix liquids and then all the astronaut has 388 00:27:27,196 --> 00:27:30,396 Speaker 2: to do is flip the switch and you can mix 389 00:27:30,556 --> 00:27:33,676 Speaker 2: back and forth with the syringes, back and forth to 390 00:27:33,716 --> 00:27:37,676 Speaker 2: get a homogeneous solution. So this gives you an opportunity 391 00:27:38,756 --> 00:27:45,036 Speaker 2: to manipulate your experiments in space, you know, and do 392 00:27:45,196 --> 00:27:47,756 Speaker 2: a wide range of different experiments. 393 00:27:47,876 --> 00:27:50,596 Speaker 1: A lab in space the dream is a lab in space. 394 00:27:50,716 --> 00:27:55,596 Speaker 2: Absolutely, you really have an opportunity to play with things 395 00:27:55,636 --> 00:28:00,516 Speaker 2: and to discover to me that you know, I'm a tinkerer, 396 00:28:01,076 --> 00:28:03,796 Speaker 2: So that that's someone I'd love to play with different 397 00:28:03,796 --> 00:28:07,396 Speaker 2: things and get surprises, and I think that's what attracted 398 00:28:07,436 --> 00:28:09,036 Speaker 2: me to doing this type of research. 399 00:28:12,676 --> 00:28:14,636 Speaker 1: We'll be back in a minute with the Lightning round. 400 00:28:25,276 --> 00:28:29,716 Speaker 1: Let's finish with the Lightning round. Do you think you'll 401 00:28:29,716 --> 00:28:30,676 Speaker 1: go to space. 402 00:28:30,676 --> 00:28:33,756 Speaker 2: Before you die? No? I don't think so. 403 00:28:34,436 --> 00:28:35,476 Speaker 1: You want to go to space? 404 00:28:38,196 --> 00:28:40,316 Speaker 2: I think if I was younger, I would want to 405 00:28:40,316 --> 00:28:43,356 Speaker 2: go to space, but I think my time has passed. 406 00:28:45,956 --> 00:28:48,596 Speaker 1: If I understand correctly, you've lived in New Jersey for 407 00:28:49,116 --> 00:28:51,516 Speaker 1: all of your life. For most of your life. What's 408 00:28:51,556 --> 00:28:53,876 Speaker 1: the most underrated Bruce Springsteen album? 409 00:28:54,676 --> 00:28:56,676 Speaker 2: I'm not really into Bruce Springsteen. 410 00:28:57,116 --> 00:29:00,916 Speaker 1: Is there another new Jersey artist of some sort who 411 00:29:00,996 --> 00:29:04,476 Speaker 1: you want to praise this at this moment. 412 00:29:05,276 --> 00:29:08,956 Speaker 2: Well, I just listened to an interview by bon Jovik. 413 00:29:09,196 --> 00:29:11,236 Speaker 1: Hey are you more of a bon Jovi? 414 00:29:11,316 --> 00:29:13,436 Speaker 2: Guys? Yeah, I would have more of a bon Jovi 415 00:29:13,596 --> 00:29:17,236 Speaker 2: and and what impressed me is the is his interaction 416 00:29:17,396 --> 00:29:22,196 Speaker 2: with trying to solve the homeless situation. And he does 417 00:29:22,876 --> 00:29:28,836 Speaker 2: a number of charity concerts as well. And this really 418 00:29:28,876 --> 00:29:32,756 Speaker 2: impressed me. I didn't know this that there was this 419 00:29:32,956 --> 00:29:34,836 Speaker 2: side of bon Jovi. 420 00:29:35,916 --> 00:29:38,796 Speaker 1: What's one thing you wish more people understood about space? 421 00:29:42,196 --> 00:29:49,596 Speaker 2: That that it's it's uh, there's tremendous opportunity to discover 422 00:29:49,876 --> 00:29:57,636 Speaker 2: new things taking advantage of what low Earth orbit laboratories 423 00:29:57,676 --> 00:30:01,356 Speaker 2: could offer to improving human health. 424 00:30:01,636 --> 00:30:05,676 Speaker 1: Is there some like dream study you would love to 425 00:30:05,716 --> 00:30:08,196 Speaker 1: do in space, like if if you weren't constrained by 426 00:30:08,716 --> 00:30:12,436 Speaker 1: lucious sticks or cost or something. Is there some intellectual 427 00:30:12,556 --> 00:30:15,156 Speaker 1: question you have or a practical question you have that 428 00:30:15,196 --> 00:30:17,836 Speaker 1: you would love to answer with a with an experiment 429 00:30:17,916 --> 00:30:18,956 Speaker 1: in microgravity? 430 00:30:19,276 --> 00:30:23,356 Speaker 2: It's that's an interesting question because I think that would 431 00:30:23,396 --> 00:30:27,396 Speaker 2: require I would love to be, you know, an astronaut, 432 00:30:27,476 --> 00:30:29,036 Speaker 2: even though I just told you I didn't want to be. 433 00:30:29,436 --> 00:30:31,916 Speaker 2: I would love to be an astronaut and have the 434 00:30:31,996 --> 00:30:35,436 Speaker 2: opportunity to tinker. I mean to have an opportunity to 435 00:30:35,436 --> 00:30:39,236 Speaker 2: do a wide range of different experiments and and and 436 00:30:40,036 --> 00:30:45,996 Speaker 2: you know, experience them firsthand, you know, and being allowed 437 00:30:46,036 --> 00:30:49,956 Speaker 2: to do the second generation. Oh I found this. Wow, 438 00:30:50,276 --> 00:30:52,236 Speaker 2: Why didn't I try this? Why do I try that? 439 00:30:52,276 --> 00:30:54,636 Speaker 2: Why don't I try this? You know? I just love 440 00:30:54,716 --> 00:30:59,116 Speaker 2: that process, and right now you don't have that opportunity 441 00:30:59,196 --> 00:31:04,556 Speaker 2: to do iterative experiments. Yeah, so tinkering. I'd love to 442 00:31:04,676 --> 00:31:05,636 Speaker 2: be able to tinker. 443 00:31:06,596 --> 00:31:09,676 Speaker 1: Maybe you need like a remote control robot, right, you 444 00:31:09,716 --> 00:31:11,876 Speaker 1: need a lab up on the space station with a 445 00:31:11,956 --> 00:31:14,876 Speaker 1: robot that you can drive from like a joystick on Earth. 446 00:31:14,916 --> 00:31:16,156 Speaker 1: I feel like that might do it. 447 00:31:16,236 --> 00:31:18,916 Speaker 2: Yeah, that would be that would be a step forward. 448 00:31:19,076 --> 00:31:22,556 Speaker 1: Yes, it seems not impossible. 449 00:31:22,996 --> 00:31:23,676 Speaker 2: No, it's not. 450 00:31:30,516 --> 00:31:33,076 Speaker 1: Paul Record is a scientist. He works in the Department 451 00:31:33,156 --> 00:31:37,356 Speaker 1: of Protein and Structural Chemistry at MERK. Today's show was 452 00:31:37,396 --> 00:31:40,796 Speaker 1: produced by Gabriel Hunter Chang. It was edited by Lyddy 453 00:31:40,876 --> 00:31:44,676 Speaker 1: Jean Kott and engineered by Sarah Brugeir. You can email 454 00:31:44,756 --> 00:31:48,676 Speaker 1: us at problem at Pushkin dot FM. I'm Jacob Goldstein 455 00:31:48,716 --> 00:31:50,956 Speaker 1: and We'll be back next week with another episode of 456 00:31:50,956 --> 00:32:02,676 Speaker 1: What's Your Problem.