WEBVTT - Drugs in Space 0:00:15.356 --> 0:00:22.716 Pushkin. One subject we've discussed from time to time on 0:00:22.796 --> 0:00:27.916 this show is space outer space for obvious reasons, you know, 0:00:28.116 --> 0:00:32.316 Final Frontier, etc. Another subject we've done a bunch of 0:00:32.356 --> 0:00:37.396 episodes about drug research, figuring out new and better ways 0:00:37.436 --> 0:00:41.596 to make new medicines. Also for obvious reasons, it's high 0:00:41.676 --> 0:00:46.916 stakes life or death innovation. Today we're combining those two subjects. 0:00:47.276 --> 0:00:57.076 It's a show about drug research in space. I'm Jacob 0:00:57.116 --> 0:00:59.316 Goldstein and this is What's Your Problem, the show where 0:00:59.356 --> 0:01:02.436 I talk to people who are trying to make technological progress. 0:01:02.996 --> 0:01:06.036 My guest today is Paul Reiker. He's a research scientist 0:01:06.076 --> 0:01:09.476 at the drug company Merk. Paul's problem is this, how 0:01:09.476 --> 0:01:12.876 can you run experiments in space to make better drugs 0:01:12.916 --> 0:01:15.756 on Earth. To be clear, Paul has not gone to 0:01:15.796 --> 0:01:19.076 space himself, but over the past thirty or so years, 0:01:19.156 --> 0:01:22.076 he has sent tubes full of proteins and drugs up 0:01:22.156 --> 0:01:25.556 to space, first on the Space Shuttle and more recently 0:01:25.636 --> 0:01:29.276 on rockets to the International Space Station, and he's instructed 0:01:29.316 --> 0:01:32.556 astronauts on how to carry out dozens of experiments in space. 0:01:33.636 --> 0:01:35.916 One of Paul's more recent experiments looked at a common 0:01:35.916 --> 0:01:40.836 type of drug called monoclonal antibodies. Monoclonal antibodies are used 0:01:40.836 --> 0:01:44.436 to treat cancer, among other diseases, and they're currently very 0:01:44.556 --> 0:01:48.316 time consuming and very expensive to deliver, and what Paul 0:01:48.396 --> 0:01:51.796 was trying to figure out was a cheaper, faster way 0:01:51.796 --> 0:01:55.476 to deliver those drugs. We'll talk about that experiment later 0:01:55.476 --> 0:02:01.476 in the show. Paul specializes in crystallization, basically getting molecules 0:02:01.476 --> 0:02:05.076 to form crystal structures, and crystallization is important in the 0:02:05.156 --> 0:02:07.916 drug business in a few ways. For one thing, it's 0:02:07.956 --> 0:02:11.836 really important for study the molecules that drugs target, and 0:02:11.996 --> 0:02:14.996 for another, crystallization plays an important role in the process 0:02:15.036 --> 0:02:18.516 of manufacturing drugs. So to start, I asked Paul, what 0:02:18.596 --> 0:02:22.556 are the reasons for going to space to do crystallization experiments? 0:02:23.076 --> 0:02:27.996 Okay, one is the obvious. One is sedimentation. We all 0:02:28.036 --> 0:02:32.276 see astronauts floating in space. So when you go grow 0:02:32.356 --> 0:02:37.196 crystals in space, they too remain suspended in space as 0:02:37.236 --> 0:02:42.036 they grow, and this suspended particle then has an opportunity 0:02:42.116 --> 0:02:46.316 then to grow more perfect than it would if it 0:02:46.396 --> 0:02:51.076 was sedimenting, dropping in the solution as it was being formed. 0:02:51.916 --> 0:02:53.836 So on Earth, when you're trying to do this you 0:02:53.916 --> 0:02:57.116 have this problem, which is the particles sync to the 0:02:57.116 --> 0:03:00.756 bottom like whatever correct coffee grounds in a cup or something. 0:03:00.796 --> 0:03:03.156 But when you're in space, you don't have that problem 0:03:03.196 --> 0:03:05.436 because there is no sinking and there is no ground. 0:03:05.676 --> 0:03:09.476 Right. And the second property we'd like to take advantage 0:03:09.516 --> 0:03:14.956 of is that molecules move more slowly in space. So 0:03:15.436 --> 0:03:21.996 processes that involve adding molecules to say, like a crystal, 0:03:22.916 --> 0:03:26.876 the molecules have a chance then to be discriminate to 0:03:26.876 --> 0:03:32.036 get the best molecule fit within the crystal lattice. 0:03:32.236 --> 0:03:35.956 So okay, so now we know why space is a 0:03:35.996 --> 0:03:39.916 good place to really you're trying to form crystals fundamentally, right, 0:03:39.916 --> 0:03:44.316 it's a good place to cause molecules to crystallize for 0:03:44.396 --> 0:03:48.476 the reasons you articulated. I don't want to do all 0:03:48.556 --> 0:03:51.556 thirty years of your working on crystals in space, but 0:03:51.636 --> 0:03:54.076 I wonder if there's like a moment from the kind 0:03:54.116 --> 0:03:58.196 of early Space Shuttle era, like what was one kind 0:03:58.236 --> 0:04:01.996 of important early finding you had from your work on 0:04:02.036 --> 0:04:02.756 the Space Shuttle. 0:04:03.836 --> 0:04:10.156 I have a interesting but very sad story to say 0:04:10.196 --> 0:04:15.276 about that. One of the last flights we'd Space Shuttle 0:04:15.316 --> 0:04:19.796 flights that we did was STS one o seven. That 0:04:19.956 --> 0:04:24.596 Space Transportation System one O seven and that was Columbia 0:04:26.076 --> 0:04:31.316 went up in January two thousand and three, and we 0:04:31.316 --> 0:04:36.956 were trying to grow large crystals suitable for structural studies, 0:04:38.396 --> 0:04:42.876 and I uniquely had the opportunity since one of the 0:04:42.916 --> 0:04:47.676 people in our team was retiring, so we got to 0:04:47.676 --> 0:04:54.196 go to the to the launch site of Columbia. The 0:04:54.316 --> 0:04:58.236 night before launch, we went one hundred and thirty feet 0:04:58.356 --> 0:05:01.476 up in the air onto a scaffolding, up into the 0:05:01.516 --> 0:05:05.196 top of where the nose of the shuttle was, and 0:05:05.236 --> 0:05:10.676 it was it was cold, freezing cold. Little did we 0:05:10.756 --> 0:05:15.956 know but the next day, upon launch, a frozen chunk 0:05:16.236 --> 0:05:21.116 of that solid rocket booster would fall and hit the 0:05:21.156 --> 0:05:26.556 wing of Space Shuttle Columbia, and that, upon re entry 0:05:26.876 --> 0:05:33.796 two weeks later, would cause the breakup of Columbia over Texas. 0:05:33.956 --> 0:05:38.596 There was a debris field over sixty three miles for that. 0:05:39.356 --> 0:05:41.716 And the death of the astronauts right, just yes. 0:05:42.116 --> 0:05:45.996 So NATS at that point decided that they would focus 0:05:46.156 --> 0:05:51.796 on doing building the International Space Station and no longer 0:05:52.476 --> 0:05:59.236 spend time with secondary projects like this. About three four 0:05:59.276 --> 0:06:05.876 months after this disaster, I got a call from NASA 0:06:05.956 --> 0:06:09.956 and said we found some of your bottle. I flew 0:06:10.196 --> 0:06:14.636 one hundred small one mL bottles and they said, we 0:06:14.716 --> 0:06:16.516 found a few of them. Would you like to come 0:06:16.556 --> 0:06:19.716 down and take a look at them? So I said yes, 0:06:20.196 --> 0:06:25.836 So I go down to the shuttle reconstruction site. They 0:06:25.836 --> 0:06:31.316 had this dedicated site there and I found three vials 0:06:31.356 --> 0:06:38.916 and within those three bottles there were crystals, and those 0:06:38.996 --> 0:06:44.396 crystals when we did the X ray diffraction study, diffracted 0:06:44.436 --> 0:06:48.156 better than any crystals we had ever seen before. So 0:06:48.596 --> 0:06:53.916 one of my great honors in my life was about 0:06:53.916 --> 0:06:56.596 three months after that, NASA asked me, would you be 0:06:56.636 --> 0:07:01.396 willing to talk to the families of the astronauts and 0:07:01.516 --> 0:07:05.476 tell them about the results of your experiment. So it 0:07:05.516 --> 0:07:09.596 was a great honor for me to have this opertunity 0:07:10.596 --> 0:07:20.076 to hopefully give some consolation to the to the families 0:07:21.196 --> 0:07:23.996 about you know, we did get some science from this 0:07:24.716 --> 0:07:27.876 and give them some relief in their suffering. 0:07:30.276 --> 0:07:35.876 And what are the practical implications of having crystals that 0:07:35.956 --> 0:07:38.476 diffract really well? Why is that meaningful? 0:07:39.676 --> 0:07:43.836 It allows you to see the intimate contacts that are 0:07:43.876 --> 0:07:51.436 made within the protein to design the better small molecule 0:07:51.516 --> 0:07:55.276 drugs that are in complex with those proteins. So one 0:07:55.316 --> 0:07:58.436 of the interesting things was is that the crystals that 0:07:58.916 --> 0:08:05.356 grew from that experiment was from an impure sample. We're 0:08:05.396 --> 0:08:09.556 actually looking at it for purification, and one of the 0:08:09.596 --> 0:08:14.396 impurities in there was zinc. And basically found that the 0:08:14.436 --> 0:08:18.076 reason why the crystals diffracted so much better than what 0:08:18.156 --> 0:08:21.596 we had previously seen before is because there was a 0:08:21.716 --> 0:08:27.596 zinc in between two molecules of interferon stabilizing it, allowing 0:08:27.636 --> 0:08:31.076 it to have a really stable form. So that was 0:08:31.156 --> 0:08:34.236 something that was I have to say that, you know 0:08:34.396 --> 0:08:39.556 a lot of microgravity research, you're really at the basic level, 0:08:40.436 --> 0:08:44.196 and you gives you an opportunity to really change the 0:08:44.236 --> 0:08:49.956 way you think because you're so focused on, you know, 0:08:51.196 --> 0:08:53.916 very simple steps in that process. 0:08:54.236 --> 0:08:56.956 You could see the protein more clearly than anyone had 0:08:56.996 --> 0:08:57.956 ever seen it before. 0:08:58.316 --> 0:09:01.156 Absolutely, So that was the key finding. 0:09:01.796 --> 0:09:04.356 So okay, so we get so we get, you know, 0:09:04.476 --> 0:09:08.956 now into well into the twenty first century here and 0:09:09.116 --> 0:09:12.996 there's this new class of drugs, monoclonal antibodies, that are 0:09:13.116 --> 0:09:16.596 very powerful drugs, but they're very hard to deliver, right, 0:09:16.636 --> 0:09:18.716 and this is a problem you're working on solving. So 0:09:18.796 --> 0:09:23.396 tell me about the problem with delivering monoclonal antibodies. 0:09:23.796 --> 0:09:28.076 Okay. The issue is is that still to this day, 0:09:29.076 --> 0:09:35.716 most monoclone antibody therapeutics, which are given for a range 0:09:35.756 --> 0:09:44.036 of different modalities from cancer to cardiovascular disease to effective diseases. 0:09:44.996 --> 0:09:53.156 They've really revolutionized the way pharmaceutical research has been going on. Okay, 0:09:53.636 --> 0:09:58.036 so they are very good drugs. However, in the case 0:09:58.236 --> 0:10:04.636 of oncology patients especially, they have to get an infusion 0:10:04.996 --> 0:10:09.716 every three weeks and this is usually in the hospital setting. 0:10:10.556 --> 0:10:13.316 So this is an all day affair not only for 0:10:13.436 --> 0:10:18.116 the patient, but usually a caregiver that's accompanying their patient 0:10:18.156 --> 0:10:21.276 who's taking time off from work to go for these 0:10:21.316 --> 0:10:29.636 effusions every three weeks and usually a therapy could go 0:10:29.676 --> 0:10:32.596 as long as six months to a year. So this 0:10:32.756 --> 0:10:36.676 is a tremendous impact on both the patient and the 0:10:36.796 --> 0:10:38.556 caregiver and it adds. 0:10:38.316 --> 0:10:41.916 To the expense right, non trivially. It's more expensive just 0:10:41.956 --> 0:10:44.076 because it takes more labor on the side of the 0:10:44.116 --> 0:10:48.676 hospital or the infusion center. It's a complicated, expensive, time 0:10:48.716 --> 0:10:49.676 consuming process. 0:10:49.956 --> 0:10:53.476 It's about half the cost of the delivery of the drug. 0:10:54.356 --> 0:10:59.556 Is this infusion all right, So we are looking at 0:10:59.596 --> 0:11:06.756 opportunities to make crystalline suspensions So one of the let 0:11:06.836 --> 0:11:08.596 me take a step back and say one of the 0:11:08.716 --> 0:11:12.196 issues with making well, why don't you just make a 0:11:12.316 --> 0:11:18.596 high concentrated liquid formulation that you can inject? 0:11:19.716 --> 0:11:22.156 So the issue is to be clear, Just make it 0:11:22.156 --> 0:11:24.436 be a shot, like getting a flu shot or something 0:11:24.476 --> 0:11:25.236 fast and easy. 0:11:25.396 --> 0:11:29.676 Right. So the problem is that in the liquid form okay, 0:11:30.076 --> 0:11:35.236 as you increase the concentration, it becomes thick and more 0:11:35.316 --> 0:11:42.196 difficult to inject. So I don't think most people would 0:11:42.276 --> 0:11:45.876 enjoy getting an injection that may take five to ten 0:11:45.956 --> 0:11:48.996 minutes of time in order to get the same dose 0:11:49.116 --> 0:11:53.236 as you would in infusion. It would be extremely painful. 0:11:53.676 --> 0:11:59.116 Patients would not accept that kind of a delivery system 0:11:59.276 --> 0:12:03.356 of pain pain over a long period of time. Let 0:12:03.436 --> 0:12:07.236 me put this way. So we decided to look at 0:12:07.556 --> 0:12:15.756 there was some evidence that high concentrated crystalline suspensions are 0:12:16.116 --> 0:12:22.116 lower in viscosity than the comparable liquid formulations. Okay, So 0:12:23.036 --> 0:12:28.316 we went about looking see if we could crystallize monoclonal antibodies, 0:12:29.636 --> 0:12:34.716 and we had success with one monol anti monoclony antibody, 0:12:35.276 --> 0:12:41.396 and ultimately we hit discovered conditions for crystallizing pambrolasm app, 0:12:42.036 --> 0:12:49.516 which is a active pharmaceutical ingredient for one of our oncology. 0:12:48.956 --> 0:12:54.996 Drugs, and so you're studying it on Earth right, trying 0:12:55.036 --> 0:12:57.236 to understand if you can get it into a crystal 0:12:57.236 --> 0:13:00.796 structure so that so that it could be given as 0:13:00.796 --> 0:13:05.236 a quick injection rather than as a long infusion. What's like? 0:13:06.236 --> 0:13:09.796 What's why? Like, you're going to go to space. Spoil 0:13:09.876 --> 0:13:11.396 the story. You're going to go to space. You're going 0:13:11.436 --> 0:13:13.556 to send something up to space to study, But why 0:13:13.876 --> 0:13:16.116 did you try and do it on Earth first? And 0:13:16.156 --> 0:13:16.796 did it work? 0:13:16.996 --> 0:13:21.396 Absolutely? It works? The question is can you make it better? 0:13:21.796 --> 0:13:25.996 We always like to come up with the best therapeutic 0:13:26.156 --> 0:13:31.276 that we can deliver that has, you know, the stability 0:13:31.596 --> 0:13:37.196 and properties that we're looking for in a final product. 0:13:38.076 --> 0:13:41.276 And then second to that, we're always looking at opportunities 0:13:41.316 --> 0:13:47.956 to improve the manufacture of our drugs, possibly reduce cost 0:13:49.436 --> 0:13:53.996 and then have a more stable formulation. For example, one 0:13:54.036 --> 0:13:57.836 of our goals would be to show that the a 0:13:57.956 --> 0:14:03.316 crystalline suspension, since it's inherently more stable. Does that allow 0:14:03.396 --> 0:14:08.756 you to take a monocle antibody drug that is stored 0:14:09.316 --> 0:14:13.556 in a refrigerator to now be allowed to be stable 0:14:13.756 --> 0:14:18.116 save for six months at room temperature, and therefore that 0:14:18.236 --> 0:14:22.556 has a big impact on the number of patients globally 0:14:23.076 --> 0:14:23.996 that can treat. 0:14:24.116 --> 0:14:25.956 So then if it could be a shot that is 0:14:25.956 --> 0:14:28.476 stable at room temperature, then that opens up a lot 0:14:28.516 --> 0:14:30.996 of the developing world that right now is frankly just 0:14:31.036 --> 0:14:36.556 doesn't have the infrastructure to deliver refrigerated infusion drugs. 0:14:36.596 --> 0:14:36.996 Correct. 0:14:37.476 --> 0:14:39.836 Do you just call up NASA and say, hey, NASA, 0:14:39.916 --> 0:14:42.116 it's me, I want to send something to the space station. 0:14:42.476 --> 0:14:45.476 No, that's not how it works. So let me take 0:14:45.516 --> 0:14:48.836 a step back and say that after the Space Shuttle 0:14:49.356 --> 0:14:56.516 Columbia broke apart over Texas, there was no microgravity research 0:14:56.916 --> 0:15:02.956 actively research going on to about twenty ten, two eleven, 0:15:03.676 --> 0:15:08.636 and the US Congress said, we built this station, we 0:15:08.716 --> 0:15:12.236 have this beautiful laboratory in space, and it's being underutilized. 0:15:12.836 --> 0:15:18.356 So they set up a nonprofit called the Center for 0:15:18.396 --> 0:15:22.796 the Advancement of Science in Space and allowed them to 0:15:22.916 --> 0:15:28.756 manage science on the International Space Station. So about twenty 0:15:28.836 --> 0:15:35.316 eleven twenty twelve, somebody from CASES reached out to me 0:15:35.396 --> 0:15:40.396 and said, would you be interested in doing some microgravity research? 0:15:40.836 --> 0:15:42.596 Come up with a proposal. 0:15:42.876 --> 0:15:45.276 That's a nice call to get yes, And so you 0:15:45.396 --> 0:15:50.716 proposed this crystallization research on a monoclonal atta body and 0:15:50.756 --> 0:15:53.556 they say yes, and what happens? 0:15:54.196 --> 0:15:57.716 All right, So we were at this time was the 0:15:57.756 --> 0:16:03.316 early stages of where SpaceX, the Falcon nine rockets were 0:16:03.516 --> 0:16:11.516 starting to deliver their Dragon module to resupply missions to 0:16:11.636 --> 0:16:19.276 the International Space Station, and we got manifested in twenty 0:16:19.356 --> 0:16:23.796 fourteen to crystallize a monoclone at a body. 0:16:24.956 --> 0:16:27.516 Manifested in this context, it's not some new age tournament. 0:16:27.556 --> 0:16:29.516 Means you got put on the list of stuff that 0:16:29.596 --> 0:16:30.436 gets to go up there. 0:16:30.676 --> 0:16:33.316 Yes, that's what it means. You know. It was basically 0:16:37.596 --> 0:16:39.996 these are all the you know NASA terms. You know 0:16:40.076 --> 0:16:45.116 you're manifested, you know. So we always do the same 0:16:45.196 --> 0:16:48.076 experiment on ground that we do in space. 0:16:48.316 --> 0:16:51.036 Altimatically as a control control. 0:16:51.316 --> 0:16:53.916 And not only that, we usually do it in triplicate 0:16:55.116 --> 0:16:57.956 to ensure that, you know, it's not a one off 0:16:58.116 --> 0:17:00.596 or something that's not you know what I mean. 0:17:01.516 --> 0:17:02.836 I mean, if you're sending one of them all the 0:17:02.876 --> 0:17:04.636 way to space, you might as well do three on hearth. 0:17:04.916 --> 0:17:07.596 We do we well, we do three in space too. 0:17:07.996 --> 0:17:11.956 Oh interesting, so that it's not in of one. 0:17:11.716 --> 0:17:15.676 One at least you can show reproducibility that this is 0:17:15.716 --> 0:17:18.596 a real uh you know, find that you have. 0:17:18.796 --> 0:17:21.956 And so so it goes up on a Falcon nine rocket, 0:17:22.036 --> 0:17:24.956 it gets to the space station. Are you involved as 0:17:24.996 --> 0:17:27.876 it's happening, Are you like talking to the astronauts on 0:17:27.916 --> 0:17:28.476 the phone? 0:17:28.996 --> 0:17:33.476 I am. That's a good question. Usually there's there's a 0:17:33.636 --> 0:17:39.516 NASA person that's talking directly to the astronauts while they're 0:17:39.756 --> 0:17:45.556 activating our experiment. And I can actually watch by video 0:17:46.396 --> 0:17:51.636 and I can send messages through cases through NASA, uh, 0:17:51.716 --> 0:17:54.516 you know, to you know, if I see anything that's so. 0:17:54.476 --> 0:17:57.356 You're like texting the astronaut they're like wait, wait, no, 0:17:57.436 --> 0:17:59.396 turn it the other way or what like, what is 0:17:59.436 --> 0:17:59.876 going on? 0:18:00.836 --> 0:18:04.316 That's a that's a very good point we give. They 0:18:04.356 --> 0:18:09.396 have iPads that they use and there's very detail held 0:18:09.476 --> 0:18:14.436 instructions of the of the process that they're doing while 0:18:14.476 --> 0:18:17.036 doing these experiments. You've got to keep in mind that 0:18:17.116 --> 0:18:20.476 they're doing hundreds of experiments, you know. 0:18:20.716 --> 0:18:24.796 So they're astronauts on the space station. Presumably they're busy, right. 0:18:24.876 --> 0:18:28.036 They're they're very busy, and and you know, one of 0:18:28.076 --> 0:18:31.156 the things that's always impressed me is the is the 0:18:31.236 --> 0:18:38.476 fact that they're they're very uh focused, calm individuals. 0:18:38.636 --> 0:18:40.836 I feel like that's what you'd really want to optimize 0:18:40.876 --> 0:18:44.436 for in selecting an astronaut. Right focused is what I 0:18:44.476 --> 0:18:46.636 would hire for if I was hiring an astronaut. 0:18:46.876 --> 0:18:51.516 And they're curious too. They they they see their unique 0:18:51.916 --> 0:18:57.156 opportunity to impact science, and you can tell that they're 0:18:57.236 --> 0:19:00.036 enjoying what they're doing. You know, it's a I always 0:19:00.076 --> 0:19:06.316 found them to be extremely interesting people, you know, inquisitive people. 0:19:09.636 --> 0:19:12.876 In a minute, Paul's tubes come back from space and 0:19:12.916 --> 0:19:24.796 he gets to look at his space crystals. That's Paul 0:19:24.956 --> 0:19:27.996 how he gets the results of his experiments from space. 0:19:28.516 --> 0:19:30.916 Like what happens after his crystals come back. 0:19:31.516 --> 0:19:36.996 In the early days, the Dragon module would parachute down 0:19:37.116 --> 0:19:41.356 in the Pacific Ocean off of California, and there would 0:19:41.396 --> 0:19:46.876 be a tugboat that would go and would pluck that 0:19:47.436 --> 0:19:50.476 Dragon module out of the ocean. It would be two 0:19:50.556 --> 0:19:55.116 days back to the harbor and Long Beach and I 0:19:55.156 --> 0:19:59.196 would go there. And I always thought it was hysterical 0:19:59.316 --> 0:20:02.836 because if you were in Kennedy Space Center, there's so 0:20:03.036 --> 0:20:07.036 much security you can't get near or anything. When this 0:20:07.236 --> 0:20:11.236 boat gets to the dock, Long beach. They plucked this 0:20:11.316 --> 0:20:13.356 thing out of the water, put it up on a 0:20:13.436 --> 0:20:16.836 on a on a dock. They set up some folding 0:20:16.916 --> 0:20:20.596 tables and said, here's your here's your experiment. 0:20:20.236 --> 0:20:23.996 Here's your stuff. It's just like a yard sailor's stuff. 0:20:24.076 --> 0:20:29.156 Like picking up fish at the dock and they hand 0:20:29.196 --> 0:20:31.716 it over. And I would always be laughing hysterical as 0:20:31.756 --> 0:20:33.356 they would do this. You know what I mean. 0:20:33.996 --> 0:20:36.516 So you go, you walk up to the table, you say, 0:20:36.516 --> 0:20:39.036 those are my tubes. They give you the tubes and 0:20:39.076 --> 0:20:41.596 then what do you go look at them under a microscope? 0:20:41.676 --> 0:20:42.636 Like what do you actually do? 0:20:43.196 --> 0:20:46.796 We? We we take we take the experiments then and 0:20:46.916 --> 0:20:49.756 believe it or not. In the early days, we would 0:20:49.796 --> 0:20:53.516 just I was this was before that there was so 0:20:53.596 --> 0:20:59.316 many regulations about flying. I would have a cooler that 0:20:59.436 --> 0:21:03.476 I would keep and and carry the cooler back on 0:21:03.556 --> 0:21:07.556 the flight back to New Jersey. Then to do analyze 0:21:07.596 --> 0:21:08.796 the experiment. 0:21:08.716 --> 0:21:10.636 Like I just think it's a cooler full of beer 0:21:10.716 --> 0:21:12.516 or something, not your perfect crystals. 0:21:12.516 --> 0:21:13.556 You can't do that now. 0:21:13.716 --> 0:21:16.076 But by twenty sixteen, how are you doing it? On 0:21:16.116 --> 0:21:18.276 this particular one? It was twenty sixteen, right, what do 0:21:18.316 --> 0:21:19.476 you what do you'd actually. 0:21:19.276 --> 0:21:25.996 Do twenty sixteen. We flew one hundred one mL bottles, 0:21:26.156 --> 0:21:29.116 So these are all different connections conditions. 0:21:29.156 --> 0:21:33.356 Looking at one millter's tiny one hundred tiny little little bottles. 0:21:34.956 --> 0:21:41.996 And we get our experiment back and then we at 0:21:41.996 --> 0:21:46.796 that point the dragon was parachuting down in the Gulf 0:21:46.836 --> 0:21:52.956 of Mexico, and there's a helicopter that then picks up 0:21:53.596 --> 0:21:58.116 the Dragon module brings it to Kennedy Space Center and 0:21:58.156 --> 0:22:02.196 then within two hours I have the experiment. 0:22:02.476 --> 0:22:05.556 And so what do you see that first look, this 0:22:05.636 --> 0:22:07.636 thing's been up to space, it's been back. You look 0:22:07.676 --> 0:22:09.876 at it. What do you see when you look at it? 0:22:10.476 --> 0:22:16.316 Well, yeah, these crystals that are extremely small. Sure, so 0:22:17.116 --> 0:22:22.036 it requires looking at the microscope, but since it's concentrated, 0:22:22.916 --> 0:22:27.436 we can immediately tell that what we sent up was clear. 0:22:27.636 --> 0:22:32.396 A clear liquid is now a paste, you know what 0:22:32.436 --> 0:22:35.036 I mean, a white paste, and that looking at it 0:22:35.076 --> 0:22:37.396 closely on the microscope, we could see that there were 0:22:37.436 --> 0:22:42.236 crystals that were there. So what was what was unique 0:22:42.316 --> 0:22:47.276 about the SpaceX ten experiment that we did with pen 0:22:47.396 --> 0:22:51.396 roles am ab is. Remember the goal was to get large, big, 0:22:51.436 --> 0:22:56.036 single crystals. Well, we had one group of experiments where 0:22:56.076 --> 0:22:59.316 we got really really small crystals and a lot of them, 0:23:00.036 --> 0:23:04.636 And I said, what's going on? So the ground experiment 0:23:04.716 --> 0:23:12.316 comparable ground experiment had larger particles that were less homogeneous, 0:23:12.436 --> 0:23:18.276 so the overall population was more broad whereas it's more heterogeneous. 0:23:18.276 --> 0:23:23.196 It was correct. Yeah, okay, So we thought this would 0:23:23.196 --> 0:23:27.076 be an excellent opportunity to look at these two types 0:23:27.316 --> 0:23:31.636 of results and see whether it makes a difference. Are 0:23:31.676 --> 0:23:37.956 they less viscous and do they show better injectability properties? 0:23:38.796 --> 0:23:42.836 And what we found was is that the smaller particles 0:23:42.836 --> 0:23:49.956 that more uniform gave lower viscosity better rejectability properties. 0:23:50.116 --> 0:23:51.836 So that's what you want. 0:23:52.236 --> 0:23:54.436 That's what we want, and it was not where we 0:23:54.476 --> 0:23:58.116 were looking. We were we were up in the range 0:23:58.276 --> 0:24:02.316 of particles that were like ten to thirty microns, and 0:24:02.356 --> 0:24:04.876 then all of a sudden we had particles that were 0:24:04.916 --> 0:24:08.036 really small and they showed this result. 0:24:08.516 --> 0:24:12.276 So it's a prize. You didn't expect to get small 0:24:13.076 --> 0:24:14.556 small particles. 0:24:14.236 --> 0:24:18.436 Correct, right, huh. So what we did then once we 0:24:18.556 --> 0:24:24.036 got that result was we came up with processes on 0:24:24.236 --> 0:24:31.436 Earth that would mimic those results that we got in microgravity, 0:24:32.316 --> 0:24:35.356 and then we were able to get a high density, 0:24:36.556 --> 0:24:39.476 high yielding process from that. 0:24:39.796 --> 0:24:43.636 Huh, So is is the hope then that that this 0:24:43.756 --> 0:24:49.036 can lead to injectable versions not just of this particular 0:24:49.236 --> 0:24:54.036 monoclonal antibody, but of monoclonal antibodies more generally. Absolutely, So 0:24:54.116 --> 0:24:55.796 I want to talk about what you're working on next, 0:24:56.476 --> 0:24:58.956 and I'm curious in particular about how you've been inspired 0:24:58.956 --> 0:25:00.876 by an astronaut named Kate Robbins. 0:25:01.516 --> 0:25:08.396 She was a molecular biologist from Stanford slash astronaut, and 0:25:08.716 --> 0:25:12.436 I watch the video of her when she was in 0:25:12.516 --> 0:25:17.316 a mission twenty sixteen where she said she can take 0:25:17.396 --> 0:25:21.556 one personal item up to space. So she takes a 0:25:21.556 --> 0:25:26.356 pipetta up to space and she just starts moving liquids 0:25:26.436 --> 0:25:29.956 around the same way you do on Earth. And this 0:25:30.156 --> 0:25:34.036 just blew me away because all of my experiments that 0:25:34.076 --> 0:25:39.756 I had done before that were always in lock down hardware, 0:25:39.996 --> 0:25:42.676 you know what I mean, with minimum conta. 0:25:42.916 --> 0:25:45.676 Like, the idea that somebody could be pipetting in space, 0:25:45.716 --> 0:25:48.796 to you as a sort of working scientist, is amazing. 0:25:48.916 --> 0:25:50.636 Oh my god, if we could pipet up there, we 0:25:50.676 --> 0:25:51.436 can do anything. 0:25:51.676 --> 0:25:56.356 Absolutely, because up until that point we always felt as 0:25:56.396 --> 0:25:59.876 though we had to take processes that we did on 0:25:59.996 --> 0:26:05.676 Earth and then get them to Jerry rigged them to 0:26:05.676 --> 0:26:09.036 get the work in microgravity hardware. So that was always 0:26:09.196 --> 0:26:14.356 the issue. Okay. So when I saw you know, doctor 0:26:14.436 --> 0:26:19.756 Kate Rubens start pipetting in space, it opened it. It 0:26:20.036 --> 0:26:22.276 like blew me away. I was sitting in the audience 0:26:22.316 --> 0:26:23.996 and I was looking around and said, did you just 0:26:24.156 --> 0:26:26.516 see that? Did you just see what she was doing? 0:26:27.356 --> 0:26:29.356 Because what what does it mean to you when you 0:26:29.356 --> 0:26:29.716 see that? 0:26:29.756 --> 0:26:29.796 What? 0:26:29.996 --> 0:26:31.876 What? What do you think? What does it mean to you? 0:26:32.236 --> 0:26:34.516 I mean what it says to me, and it may 0:26:34.636 --> 0:26:38.156 sound strange, is that you can you can do the 0:26:38.196 --> 0:26:42.796 same thing that Edison did one hundred years ago. So 0:26:42.836 --> 0:26:47.356 you can you can have a laboratory or a base, okay, 0:26:47.916 --> 0:26:50.436 and you can move liquids and you can play around 0:26:50.516 --> 0:26:53.996 with different things, and it just opens up, you know, 0:26:54.316 --> 0:27:00.156 a whole other world of opportunities for discovery, in innovation 0:27:00.876 --> 0:27:05.196 in real time. So one pipett of revolution in one 0:27:05.196 --> 0:27:06.636 pipet and one pipette. 0:27:06.956 --> 0:27:08.796 So what do you want to do with this new 0:27:09.956 --> 0:27:11.476 world of possibilities? 0:27:11.676 --> 0:27:16.796 So what we did internally here is we came up 0:27:16.836 --> 0:27:22.516 with our own three D printed hardware. Okay, so that 0:27:22.596 --> 0:27:27.156 we could mix liquids and then all the astronaut has 0:27:27.196 --> 0:27:30.396 to do is flip the switch and you can mix 0:27:30.556 --> 0:27:33.676 back and forth with the syringes, back and forth to 0:27:33.716 --> 0:27:37.676 get a homogeneous solution. So this gives you an opportunity 0:27:38.756 --> 0:27:45.036 to manipulate your experiments in space, you know, and do 0:27:45.196 --> 0:27:47.756 a wide range of different experiments. 0:27:47.876 --> 0:27:50.596 A lab in space the dream is a lab in space. 0:27:50.716 --> 0:27:55.596 Absolutely, you really have an opportunity to play with things 0:27:55.636 --> 0:28:00.516 and to discover to me that you know, I'm a tinkerer, 0:28:01.076 --> 0:28:03.796 So that that's someone I'd love to play with different 0:28:03.796 --> 0:28:07.396 things and get surprises, and I think that's what attracted 0:28:07.436 --> 0:28:09.036 me to doing this type of research. 0:28:12.676 --> 0:28:14.636 We'll be back in a minute with the Lightning round. 0:28:25.276 --> 0:28:29.716 Let's finish with the Lightning round. Do you think you'll 0:28:29.716 --> 0:28:30.676