WEBVTT - The Future of Clinical Trials 0:00:00.160 --> 0:00:07.200 Brought to you by Toyota. Let's go places. Welcome to 0:00:07.400 --> 0:00:15.200 Forward Thinking. Hey there, and welcome to Forward Thinking, the 0:00:15.320 --> 0:00:18.160 podcast that looks at the future and said soon turned 0:00:18.160 --> 0:00:21.760 out had a heart of glass. I'm Jonathan, I'm Lauren Focan, 0:00:21.920 --> 0:00:25.280 and I'm Joe McCormick. So you know, I I pitched 0:00:25.320 --> 0:00:29.520 this idea for this episode. Um and uh, it's all 0:00:29.560 --> 0:00:34.199 about organs on chips, and you guys really when nuts 0:00:34.240 --> 0:00:37.760 with the whole research and it was only about five 0:00:37.760 --> 0:00:40.120 hours into it that we suddenly realized that it's it's 0:00:40.360 --> 0:00:44.000 it's not about snack food. No, it is not about 0:00:44.240 --> 0:00:47.199 putting like sheep organs on French fries and what they 0:00:47.200 --> 0:00:50.240 would call that in England. Well, I'm a really big fan. 0:00:50.320 --> 0:00:52.960 Actually if the entire genre of kind of you know, 0:00:53.360 --> 0:00:56.720 the awful and the chips are delicious. Ye, you're you're 0:00:56.720 --> 0:00:58.760 talking awful as an o F F a L right, 0:00:58.800 --> 0:01:03.600 not not a WF you well were We were really 0:01:03.600 --> 0:01:06.480 really we're really interested in in covering that in the 0:01:06.520 --> 0:01:09.319 future of it. But as it turns out, the the 0:01:09.400 --> 0:01:14.240 what organs on chips actually are is pretty darn fascinating 0:01:14.280 --> 0:01:19.119 and it's all about transforming how clinical tests would be 0:01:19.200 --> 0:01:21.760 carried out. But in order for us to talk about transforming, 0:01:22.120 --> 0:01:23.760 we kind of have to lay some groundwork, right, We 0:01:23.800 --> 0:01:27.559 need to talk about how clinical trials happen. How, How 0:01:27.800 --> 0:01:32.679 do how does the medical profession evaluate and regulate things 0:01:32.720 --> 0:01:36.920 like drugs? For example? Yeah, because you can't just make 0:01:36.959 --> 0:01:39.120 a drug and put it in a bottle and then 0:01:39.160 --> 0:01:41.760 go sell it to anybody. Can Well you can, but 0:01:42.040 --> 0:01:46.000 legally you'd be culpable for that. Anything that you claim 0:01:46.080 --> 0:01:49.800 has a pharmacological effect, you would then be probably brought 0:01:49.920 --> 0:01:53.000 under the uh the attention of the Food and Drug 0:01:53.040 --> 0:01:57.120 Administration here in the United States or whatever other regulatory 0:01:57.160 --> 0:01:59.640 body you have, and whatever other countries. What if I 0:01:59.680 --> 0:02:02.600 call it a natural remedy, So now then you get 0:02:02.640 --> 0:02:06.800 a little more leeway in some countries. But that's that's 0:02:06.840 --> 0:02:09.760 a different conversation. Okay, No, Let's let's look at actual 0:02:09.880 --> 0:02:14.080 mainstream pharmaceuticals. Let's say that I am a researcher and 0:02:14.120 --> 0:02:17.519 I've come up with a new compound that I think 0:02:17.560 --> 0:02:22.600 will help cure some disease. What happens before I can 0:02:22.639 --> 0:02:25.640 actually give that to people to help them? How? What 0:02:25.680 --> 0:02:27.600 are all the processes I have to go to find 0:02:27.600 --> 0:02:29.720 out whether or not it works, whether or not it's safe, 0:02:29.760 --> 0:02:33.880 to get all the government approvals what happens. Luckily we 0:02:33.919 --> 0:02:37.800 have Lauren here, who is our our medical guru. So, Lauren, 0:02:38.080 --> 0:02:41.240 do you feel comfortable tackling some of this, Yeah, sure, totally. 0:02:41.760 --> 0:02:43.920 First of all, it's going to depend on what country 0:02:43.960 --> 0:02:46.320 you're in, because regulations are going to be different under 0:02:46.360 --> 0:02:50.480 any any different government obviously, but the pre clinical and 0:02:50.520 --> 0:02:54.200 clinical trial procedures are similar around the world. We're going 0:02:54.280 --> 0:02:57.800 to talk specifically about the US ones right now, so 0:02:57.880 --> 0:03:01.920 let us talk about those two phases, the preclinical and 0:03:02.160 --> 0:03:05.320 the clinical. During the pre clinical first, Joe, if you 0:03:05.360 --> 0:03:09.560 have made a compound, that's that's heads above many other 0:03:09.639 --> 0:03:12.840 people in the research industry right this very moment. It 0:03:12.919 --> 0:03:17.000 takes a lot of doing to actually create a compound 0:03:17.080 --> 0:03:19.840 that you think is going to solve a particular problem. 0:03:19.880 --> 0:03:23.079 You know, you might be trying to inhibit or amplify 0:03:23.200 --> 0:03:27.040 a particular enzyme that does something or isn't doing something correctly. 0:03:27.680 --> 0:03:31.240 And so once once you've got a bunch of computer 0:03:31.400 --> 0:03:35.520 modeling and in vitro, that's that's lab dish testing done, 0:03:35.960 --> 0:03:40.400 then you can move forward to the next part. Okay, 0:03:40.440 --> 0:03:43.320 so I've done initial testing, I've I've got a compound, 0:03:43.360 --> 0:03:46.120 I've settled on what do I need to do next? Next, 0:03:46.280 --> 0:03:49.360 you need to test it in living animals. And I 0:03:49.400 --> 0:03:52.480 know that that this is a very sensitive and squeamish 0:03:52.480 --> 0:03:55.600 topic for a lot of people. And I absolutely understand that. 0:03:55.680 --> 0:03:59.120 I don't think that anyone medical researchers included are twisting 0:03:59.160 --> 0:04:01.080 their mustaches go and like, yes, we are going to 0:04:01.160 --> 0:04:03.880 hurt these rats today, at least I hope not that 0:04:03.880 --> 0:04:06.720 would be I'm very fond of rats personally. But it's 0:04:06.800 --> 0:04:08.960 incredibly important and we'll get into that a little bit 0:04:09.040 --> 0:04:12.400 later on. Um, but let us suffice it to say 0:04:12.440 --> 0:04:15.160 at the current moment that different animals are used for 0:04:15.200 --> 0:04:19.560 their similarities to two different human systems. For example, pigs 0:04:19.560 --> 0:04:23.880 cardiovascular systems are surprisingly similar to humans. Uh though, rats 0:04:23.920 --> 0:04:26.600 are the go to for lots of drug testing, especially 0:04:26.640 --> 0:04:29.400 at these early stages that we're talking about, right, So 0:04:29.640 --> 0:04:32.600 that's probably because lots of mammals are pretty much all 0:04:32.760 --> 0:04:35.280 mammals share a lot of things in common, even though 0:04:35.279 --> 0:04:38.760 they don't necessarily share everything. Uh yeah, we also don't 0:04:38.800 --> 0:04:41.520 share many, many, many things, and that's part of why 0:04:41.560 --> 0:04:44.720 this whole organ onic chip discussion has been rearing up. 0:04:45.080 --> 0:04:48.080 But uh, the things that you're looking for with animal 0:04:48.120 --> 0:04:51.159 testing include like how much of a compound will be 0:04:51.200 --> 0:04:53.479 absorbed by the body, or how the body will break 0:04:53.520 --> 0:04:57.839 it down into into the metabolites, or the toxicity of 0:04:57.839 --> 0:05:00.960 the compound and its metabolites at levels that are likely 0:05:01.000 --> 0:05:03.320 to be used for the intended purpose of the drug, 0:05:03.800 --> 0:05:07.080 or how quickly the compound and its metabolites will be 0:05:07.160 --> 0:05:09.880 excreted from the body, all of these being of course, 0:05:09.960 --> 0:05:12.760 very important to figuring out how a drug works. Right. So, 0:05:12.880 --> 0:05:15.760 in other words, if I take a drug and it 0:05:15.760 --> 0:05:19.960 turns out that only a tiny percentage of whatever that 0:05:20.200 --> 0:05:24.600 substance is actually gets absorbed by my body, then you 0:05:24.640 --> 0:05:27.720 would you could draw the conclusion that that wasn't a 0:05:27.839 --> 0:05:32.400 very efficient use of that particular dose of drug. You 0:05:32.400 --> 0:05:35.200 could say, it's not that the drug is necessarily ineffective. 0:05:35.480 --> 0:05:37.760 It may be that you need to make up more 0:05:37.920 --> 0:05:42.240 of that that dose with other inactive elements to make 0:05:42.320 --> 0:05:46.160 up whatever that particular delivery system is. Oh sure, maybe 0:05:46.200 --> 0:05:48.440 you need to tweak the compound itself, or maybe you 0:05:48.480 --> 0:05:50.919 need to change the delivery method. Maybe we're injecting it 0:05:50.960 --> 0:05:53.039 but it needs to be taken orally. There's all kinds 0:05:53.080 --> 0:05:57.760 of I mean numerous multitudes of variables that can go 0:05:57.839 --> 0:06:00.560 into any stage of this process and it testing and 0:06:00.560 --> 0:06:04.400 it's safety, uh and and it's so complicated that traditionally 0:06:04.480 --> 0:06:07.920 computer modeling has never been good enough to substitute for 0:06:08.240 --> 0:06:11.839 actual physical animal testing. I mean, just because our bodies 0:06:11.880 --> 0:06:14.800 are so ridiculously complex and our systems are tied to 0:06:14.839 --> 0:06:18.120 each other in ways that we really don't understand yet, 0:06:18.440 --> 0:06:21.600 which sounds ridiculous being that we live in the incredible future. 0:06:21.720 --> 0:06:23.920 But we've said many times on this show that the 0:06:24.000 --> 0:06:26.280 human body is kind of one of those science things 0:06:26.279 --> 0:06:28.560 that we just don't don't have worked out yet. Well, yeah, 0:06:28.560 --> 0:06:30.520 as it turns out that if you want to learn 0:06:30.600 --> 0:06:35.240 a lot about the human body, there's some ethical issues 0:06:35.320 --> 0:06:37.360 that you have to look into. Like you can't just 0:06:37.480 --> 0:06:39.400 take a person and then say, all right, we're gonna 0:06:39.440 --> 0:06:42.279 take this one, one person apart and see what makes 0:06:42.279 --> 0:06:45.800 a human body tick. That's there are huge ethical problems 0:06:45.800 --> 0:06:49.960 with that. If you don't recognize that, Uh, why don't 0:06:50.000 --> 0:06:53.480 you go listen to stuff they don't want you to know? Podcast? 0:06:55.640 --> 0:07:03.360 The show for sociopath Love should buy oh snap, if 0:07:03.440 --> 0:07:06.640 Josh and Chuck ever listened to our show that you 0:07:08.600 --> 0:07:14.640 oh no, they're totally scy and they love us so 0:07:15.200 --> 0:07:18.920 at any rate at this stage, UM that the compound 0:07:19.000 --> 0:07:21.480 can go through a lot of these little tweaks that 0:07:21.520 --> 0:07:24.600 we were just talking about. UM, And if all goes well, 0:07:24.840 --> 0:07:29.520 the company developing the drug would submit a Investigational New 0:07:29.600 --> 0:07:32.960 Drug Application or i n D to the f d A, 0:07:33.240 --> 0:07:36.040 which is of course the Food and Drug Administration UM. 0:07:36.280 --> 0:07:39.560 The application will include the chemical and manufacturing data, the 0:07:39.600 --> 0:07:42.440 animal test results featuring a whole bunch of different safety 0:07:42.480 --> 0:07:46.440 margins and whole body effects of the compound UM, and 0:07:46.480 --> 0:07:49.400 then the reasons for proceeding to a human trial, the 0:07:49.440 --> 0:07:54.720 plans for protecting the human volunteers, and the overall testing strategy. 0:07:54.960 --> 0:07:57.880 It's going to be laid out. It's it's not it's 0:07:57.880 --> 0:08:00.480 longer than a book report, y'all right, Because I mean again, 0:08:00.600 --> 0:08:03.720 this is why animals are so important in this phase, right, Because, 0:08:04.560 --> 0:08:07.080 like you were saying, the human body being so complex. 0:08:07.240 --> 0:08:10.320 If you're taking a treatment that's targeting a specific part, 0:08:10.720 --> 0:08:13.280 like let's say it's for a disease that's found in 0:08:13.320 --> 0:08:16.400 the liver, Uh, that does not necessarily mean it won't 0:08:16.440 --> 0:08:19.400 affect other systems in the body. Yeah, the drug is 0:08:19.400 --> 0:08:22.120 not going to magnetically go to the liver and just 0:08:22.200 --> 0:08:24.720 hang out there. It's gonna get into other systems and 0:08:24.840 --> 0:08:28.880 might have unannounced side effects and announced unpredictable side effects. 0:08:28.960 --> 0:08:31.280 And and that's true in animal bodies at least as 0:08:31.320 --> 0:08:33.960 much as it is in humans. And so all of 0:08:33.960 --> 0:08:38.199 this is very sticky. But once once they've been approved 0:08:38.320 --> 0:08:40.640 on their I n D, they can move on to 0:08:40.760 --> 0:08:44.240 clinical trials, which is the official human element in all 0:08:44.280 --> 0:08:48.760 of this. So this occurs in three different phases, phases one, two, 0:08:48.760 --> 0:08:52.280 and three, which take approximately one, two, and three years 0:08:52.320 --> 0:08:55.280 to complete, respectively, although they can take very much longer 0:08:55.320 --> 0:09:00.320 than that depending During Phase one, volunteers are given very 0:09:00.360 --> 0:09:03.719 low doses of the compound, the volunteers might be healthy or, 0:09:03.840 --> 0:09:07.480 in the case of very severe diseases, actual patients, and 0:09:07.600 --> 0:09:11.240 the doses are then gradually increased to test the effects 0:09:11.240 --> 0:09:14.880 and the safety of the drug. About phase two UM. 0:09:14.920 --> 0:09:18.200 About two thirds of drugs tested will proceed onto Phase 0:09:18.240 --> 0:09:22.080 two UM, during which one hundred to three hundred patients 0:09:22.120 --> 0:09:25.520 are given the compound to help determine the most effective 0:09:25.520 --> 0:09:29.479 dose and delivery method and to continue assessing the compounds, 0:09:29.480 --> 0:09:33.000 effects and safety at at these street levels all right, 0:09:33.400 --> 0:09:35.640 um and I don't have an exact number on this one, 0:09:35.720 --> 0:09:38.079 but a lot of drugs drop out of the trial 0:09:38.160 --> 0:09:40.160 phase right here and have to kind of go back 0:09:40.160 --> 0:09:46.040 to the drawing board to be retested and reevaluated, um now. 0:09:46.200 --> 0:09:49.440 To mitigate potential harm, these first two phases are conducted 0:09:49.480 --> 0:09:52.720 with the smallest number of volunteers possible in order to 0:09:52.760 --> 0:09:57.520 gain statistically significant results. But during phase three, the testing 0:09:57.559 --> 0:10:01.360 has opened up to thousands of patients across many different populations, 0:10:01.400 --> 0:10:05.120 which um uh, population is medical jargon for a group 0:10:05.160 --> 0:10:11.160 of people with vaguely common denominators in terms of health 0:10:11.280 --> 0:10:15.079 or age or anything like that. And this is where 0:10:15.160 --> 0:10:18.480 final dosage and safety data are are sessed out, and 0:10:19.160 --> 0:10:21.440 some ten percent of drugs that have made it this 0:10:21.520 --> 0:10:25.160 far will fail to be deemed safe, all right. But 0:10:25.240 --> 0:10:28.079 for the drugs that actually make it through those three phases, 0:10:28.440 --> 0:10:31.920 they just go out into store shells, right PLoP right there. 0:10:32.080 --> 0:10:34.800 Not at all. Now now we are we are we 0:10:34.840 --> 0:10:37.480 are certainly not done yet. All of this pre clinical 0:10:37.520 --> 0:10:40.199 and clinical data is wrapped up into a new drug 0:10:40.240 --> 0:10:44.080 application or n d A in the industry and submitted 0:10:44.120 --> 0:10:46.880 back to the FDA for independent review, which can take 0:10:46.960 --> 0:10:50.360 up to an entire additional year UM during which they 0:10:50.400 --> 0:10:53.760 might ask for more data or corrections, or even stipulate 0:10:53.800 --> 0:10:58.120 a Phase four of testing. And in the end of 0:10:58.120 --> 0:11:01.680 this entire process, only one out of every five thousand 0:11:01.760 --> 0:11:05.000 to ten thousand compounds that entered pre clinical testing to 0:11:05.040 --> 0:11:08.000 begin with will ever be approved by the FDA to 0:11:08.080 --> 0:11:11.520 be marketed to the public um And even after that approval, 0:11:11.760 --> 0:11:14.360 the manufacturer has to check in quarterly with the FDA 0:11:14.440 --> 0:11:17.679 for the next three years, and prescribing physicians have the 0:11:17.720 --> 0:11:22.760 responsibility of reporting adverse reactions and and the company itself 0:11:22.960 --> 0:11:25.719 might choose to continue clinical trials to assess like long 0:11:25.840 --> 0:11:29.319 term effects and continue tweaking dosage recommendations and safety and 0:11:29.400 --> 0:11:32.840 stuff like that. Or might have side effects that just 0:11:32.960 --> 0:11:37.360 happened to be really useful for curing other problems. Ah, Yes, 0:11:37.679 --> 0:11:40.920 like a like a medicine that might be used for 0:11:41.679 --> 0:11:47.280 cardiovascular purposes that perhaps addresses a completely different issue for 0:11:47.640 --> 0:11:51.160 people who are looking for a particular solution to a 0:11:51.200 --> 0:11:53.839 particular problem. I think I know what you're talking about, 0:11:53.840 --> 0:11:56.079 But biagraa I believe is that would be the one 0:11:56.080 --> 0:11:59.880 I was specifically dancing around. So now that we've covered 0:12:00.720 --> 0:12:04.520 what about some of the issues that we've got this 0:12:04.520 --> 0:12:12.680 this incredibly large, encompassing process that is meant to make 0:12:12.760 --> 0:12:15.640 sure that whatever comes out at the end of it 0:12:15.679 --> 0:12:18.320 is the most beneficial right, that that is going to 0:12:18.600 --> 0:12:22.280 not cause harm ideally and will actually be efficacious for 0:12:22.360 --> 0:12:25.199 what it's intended to do, or the at least the 0:12:25.600 --> 0:12:29.000 horror outweighs or the benefits outweigh the horror exactly. So 0:12:29.000 --> 0:12:32.280 So what what are some of the problems with this process? 0:12:32.280 --> 0:12:37.559 I mean, clearly, we want something that's very uh you know, meticulous, 0:12:37.600 --> 0:12:40.280 so that we don't cause large amount of harm, But 0:12:40.320 --> 0:12:43.440 what are some of the drawbacks here? Well, for one, thing, 0:12:43.800 --> 0:12:46.559 sounds like it takes a really long time. Yeah, I 0:12:46.600 --> 0:12:49.640 think eight to twelve years is the average. So meanwhile, 0:12:49.679 --> 0:12:53.920 you have people suffering from whatever the drug was intended 0:12:53.960 --> 0:12:56.640 to address. I mean, assuming that it's a good drug 0:12:56.720 --> 0:12:59.000 that does work right, yeah, yeah, and it can be 0:12:59.080 --> 0:13:03.760 sped up in certain circumstances like for example, during the 0:13:03.559 --> 0:13:07.440 the the aid's outbreak in the nineteen eighties. Uh, some 0:13:07.440 --> 0:13:10.400 some drugs were pushed through very very quickly, and and 0:13:10.440 --> 0:13:13.240 that is a thing that can happen in that kind 0:13:13.320 --> 0:13:17.480 of case an extreme circumstances. But it also sounds to 0:13:17.520 --> 0:13:19.960 me like this process might might have a bit of 0:13:20.000 --> 0:13:24.080 a price tag to it. Yep. According to the Pharmaceutical 0:13:24.120 --> 0:13:27.840 Research and Manufacturers of America, as of the year two thousand, 0:13:28.200 --> 0:13:31.760 it costs more than five hundred million dollars to bring 0:13:31.840 --> 0:13:35.560 the average drug to market. And that was fourteen years ago, 0:13:35.640 --> 0:13:38.960 so as of today, it's probably a low ball. Um. 0:13:39.040 --> 0:13:42.400 Of course, not all of that is um specifically wrapped 0:13:42.480 --> 0:13:47.120 up in clinical trial, which is kind of the part 0:13:47.160 --> 0:13:50.040 that we're dancing around with the entire topic of this episode, 0:13:50.360 --> 0:13:53.360 and wherein organs on chips are going to come back 0:13:53.400 --> 0:13:57.840 to us that that might take umasily um two million 0:13:57.880 --> 0:14:00.280 dollars at the kind of low end of estimate. Now, 0:14:00.360 --> 0:14:03.319 keep that you might wonder about, you know, the pharmaceutical industry. 0:14:03.320 --> 0:14:06.840 Everyone talks about being a multibillion dollar industry, but as 0:14:06.880 --> 0:14:11.079 we've set up this this process, it requires you to 0:14:11.200 --> 0:14:16.040 have a huge amount of of cash. Just yeah, you 0:14:16.080 --> 0:14:18.640 can't you can't just jump into the market willy nilly, 0:14:18.840 --> 0:14:22.080 simply because you do have to meet these very strict 0:14:22.120 --> 0:14:25.880 standards in order to move forward. Another problem I would 0:14:25.880 --> 0:14:29.280 see with this whole process is the concept of animal testing, 0:14:29.920 --> 0:14:32.280 which can be a problem for multiple reasons. I mean, 0:14:32.360 --> 0:14:35.440 number one, there is just the the ethical concern. I 0:14:35.440 --> 0:14:37.840 mean that it's a hard question to way that. Like, 0:14:37.960 --> 0:14:40.880 you know, obviously we want to be able to create 0:14:40.920 --> 0:14:43.960 drugs that can save human lives, but you know, how 0:14:43.960 --> 0:14:45.920 many animals do you have to kill to do that, 0:14:46.040 --> 0:14:50.040 and what's what's the scale there? But beyond that, there 0:14:50.120 --> 0:14:53.920 is the question of how much can we necessarily learn 0:14:54.200 --> 0:14:57.960 from animal testing. Obviously we can learn something, so it's 0:14:58.000 --> 0:15:01.200 not saying that that's worthless course, but you know, at 0:15:01.200 --> 0:15:04.160 a certain point when you're when you move from animal 0:15:04.160 --> 0:15:07.800 testing into human testing and you realize that that things 0:15:07.840 --> 0:15:10.560 that you had previously assumed based on your animal tests 0:15:10.560 --> 0:15:13.840 are completely incorrect in a human it's it's heartbreaking for 0:15:13.880 --> 0:15:16.440 everyone involved. Yeah, there's it's a waste of time and 0:15:16.520 --> 0:15:18.920 money in life, and it's also an increase in risk. Yeah, 0:15:19.080 --> 0:15:22.400 there's there's a chance that something that had no toxicity 0:15:22.560 --> 0:15:26.240 in your animal models may be toxic in humans. Um, 0:15:26.240 --> 0:15:28.720 it's or vice versa. I mean, there are things that 0:15:28.880 --> 0:15:31.680 we humans can consume that are fine, and if an 0:15:31.680 --> 0:15:34.880 animal consumed it, it might not be able to survive 0:15:35.000 --> 0:15:37.280 or it could end up suffering at least some form 0:15:37.280 --> 0:15:40.520 of poisoning. So it's uh, the animal models are not 0:15:40.520 --> 0:15:43.800 always predictive for what will happen when you transfer that 0:15:43.920 --> 0:15:46.120 same sort of treatment over to a human. Also, keep 0:15:46.120 --> 0:15:49.960 in mind we're talking specifically about testing drugs, but other 0:15:50.000 --> 0:15:53.560 types of chemicals are also tested on animals because of 0:15:53.680 --> 0:15:58.800 similar reasons, things like cosmetics or just chemicals that humans 0:15:58.800 --> 0:16:01.560 would come into contact with than it. And so anyone 0:16:01.600 --> 0:16:04.880 who's making said chemical for some product has to be 0:16:04.960 --> 0:16:09.320 able to demonstrate what are the parameter for safety, parameters 0:16:09.360 --> 0:16:13.200 for its use. So all of that requires animal testing, 0:16:13.440 --> 0:16:17.560 and obviously, uh, you know, depending upon your personal feelings 0:16:17.600 --> 0:16:20.840 towards animal testing, this may be very disturbing to you. 0:16:21.120 --> 0:16:22.880 Oh sure, sure, I mean, you know, I think that 0:16:22.960 --> 0:16:26.720 we can all agree that. Um, if you're testing cancer treatments, 0:16:26.960 --> 0:16:30.920 then you know, I'm really sorry, Fluffy, but it's for 0:16:30.960 --> 0:16:32.640 the best. It's for the best for all of us. 0:16:33.000 --> 0:16:36.680 But if you're testing mascara, then I get that upsets 0:16:36.680 --> 0:16:39.720 people a little bit more. Yes, clearly, So one of 0:16:39.760 --> 0:16:44.960 the potential solutions for this this ethical issue is this 0:16:45.040 --> 0:16:48.760 concept of an organ on a chip, and really this 0:16:48.840 --> 0:16:53.600 would mostly concern those pre clinical phases. Lauren talked about 0:16:53.640 --> 0:16:58.480 the ones that are animal testing in particular. Potentially this 0:16:58.560 --> 0:17:02.880 particular type of technolo oology could help reduce or even 0:17:02.920 --> 0:17:06.040 eliminate the need for animal testing if it proves to 0:17:06.160 --> 0:17:10.240 be an effective enough platform. Okay, so what is an 0:17:10.320 --> 0:17:13.840 organ on a chip? All right? So it looks kind 0:17:13.880 --> 0:17:16.399 of like a little plastic chip about the size of 0:17:16.440 --> 0:17:20.399 a USB flash drive, little thumb drive. Um, not a 0:17:20.520 --> 0:17:21.920 not a full drive, but you know, just one of 0:17:21.960 --> 0:17:23.479 those little things you up on your key chain. It's 0:17:23.520 --> 0:17:26.160 about that same size. So it's a it's got these 0:17:26.200 --> 0:17:31.399 hollow micro fluidic channels that are lined with actual human cells, 0:17:31.480 --> 0:17:35.159 like living human tissue exactly. I mean, it's obviously not 0:17:35.160 --> 0:17:39.480 connected to a human but yeah, the actual the actual 0:17:39.560 --> 0:17:43.280 cells are viable cells. They aren't just you know, just 0:17:43.280 --> 0:17:46.920 just desiccated cells that actually do live. And the chip 0:17:47.040 --> 0:17:51.160 replicates the functions of a particular organ, and the organ 0:17:51.240 --> 0:17:54.720 is all dependent upon what you've lined the these micro 0:17:54.840 --> 0:17:58.439 fluidic channels with. So, for example, a lung on a 0:17:58.560 --> 0:18:01.399 chip would include a membrane that on one side is 0:18:01.440 --> 0:18:03.760 lined with lung cells, and on the other side of 0:18:03.760 --> 0:18:06.560 the membrane, the flip side, you would have human blood 0:18:06.560 --> 0:18:11.480 cells lining it, and you could have air essentially circulating 0:18:11.520 --> 0:18:15.560 across the lung cells and blood or some sort of 0:18:15.600 --> 0:18:19.920 blood simulated fluid moving across the other cells on the 0:18:19.960 --> 0:18:22.520 other side of the membrane, and the membrane itself can 0:18:22.560 --> 0:18:28.639 actually expand and contract, thus mimicking the physiological function of 0:18:28.680 --> 0:18:33.200 a lung. Okay, but we already test drugs, I believe 0:18:33.240 --> 0:18:37.280 in the pre clinical phase on like cultures like lab 0:18:37.320 --> 0:18:40.480 dishes full of cells, don't we yes, So what kind 0:18:40.520 --> 0:18:43.000 of difference would the organ on a chip make? Well 0:18:43.040 --> 0:18:45.800 a culture of living cells. Obviously it's really important to 0:18:45.920 --> 0:18:47.760 use that and to see what the effects are. But 0:18:47.800 --> 0:18:53.240 the culture of cells doesn't have the physiological function of 0:18:53.280 --> 0:18:55.520 the organ it comes from, right, It's just a collection 0:18:55.520 --> 0:18:58.360 of living cells that represent that tissue, but it's not 0:18:58.880 --> 0:19:02.240 performing functions of an organ. Okay, so we don't get 0:19:02.240 --> 0:19:05.000 to see them in action. Yeah. Yeah. It's kind of 0:19:05.040 --> 0:19:07.760 like if you were to take a gear out of 0:19:07.800 --> 0:19:10.720 a clock and just look at the gear. It's not 0:19:11.040 --> 0:19:14.480 doing anything. Uh yeah, And that the metabolic processes that 0:19:14.520 --> 0:19:17.359 any of our organs go through are going to change 0:19:17.800 --> 0:19:20.800 physically change the way that the cells are functioning. So 0:19:20.840 --> 0:19:23.600 this is a very important piece of the puzzle. So 0:19:23.800 --> 0:19:26.879 depending upon what organ you're talking about, the chip is 0:19:26.880 --> 0:19:30.359 going to perform in a specific way. Right. It's not 0:19:30.880 --> 0:19:32.800 like a lung on a chip is going to behave 0:19:32.840 --> 0:19:34.720 the same way as a bone marrow on a chip. 0:19:35.200 --> 0:19:38.040 But not unless you've got something very strange going on 0:19:38.080 --> 0:19:40.320 with your bone marrow. Yeah, that then you have some 0:19:40.400 --> 0:19:43.159 other issues. So if we go to that lung on 0:19:43.200 --> 0:19:45.879 a chip example, the chip has this air flow across 0:19:45.920 --> 0:19:48.520 the lung cells and the blood like fluid across the 0:19:48.560 --> 0:19:51.760 other cells on the other side, and this is what 0:19:51.880 --> 0:19:55.400 allows it to simulate the performance of a lung. UH. 0:19:55.400 --> 0:19:57.879 These particular types of chips are being developed by a 0:19:57.960 --> 0:20:01.679 couple of different groups. The one that I specifically was 0:20:01.760 --> 0:20:05.000 really interested in was the VS Institute, which is a 0:20:05.040 --> 0:20:08.879 biological research institute that's part of Harvard University. UH. They've 0:20:08.920 --> 0:20:14.360 created ten different organs on a chip models, including liver, gut, kidney, 0:20:14.440 --> 0:20:18.960 and bone marrow UH and UH they're looking to partner 0:20:19.000 --> 0:20:23.600 with pharmaceutical companies. UH with biologists with chemists to test 0:20:23.680 --> 0:20:25.920 these out to make sure that they are in fact 0:20:26.520 --> 0:20:31.280 good analogs for actual human organs. Um And in late 0:20:31.359 --> 0:20:35.760 July of two thousand fourteen, the department that was specifically 0:20:35.800 --> 0:20:39.240 working on organs on a chip within the VS Institute 0:20:39.880 --> 0:20:43.399 has spun off a new private company in partnership with 0:20:43.440 --> 0:20:47.439 a startup called Emulate Incorporated, which has a worldwide license 0:20:47.520 --> 0:20:51.439 to commercialize this technology platform and try and move it 0:20:51.480 --> 0:20:54.400 forward to the next phase, which would involve using these 0:20:54.400 --> 0:20:57.720 and very very uh controlled tests too. You know, you 0:20:57.840 --> 0:21:01.400 probably start actually with stuff that's already been thoroughly tested 0:21:01.600 --> 0:21:04.600 to make sure that the organ on a chip behaves 0:21:04.600 --> 0:21:06.960 in the way you would in a predictable manner exactly, 0:21:07.160 --> 0:21:10.760 so that you can prove that the technology works. Um. 0:21:10.800 --> 0:21:14.040 There's another company called Nordis in O R T I 0:21:14.240 --> 0:21:16.720 S that's also working on organ on a chip platforms. 0:21:16.720 --> 0:21:18.720 They have a goal of launching a product in two 0:21:18.760 --> 0:21:22.399 thousand and fifteen. They the company itself launched back in 0:21:22.440 --> 0:21:24.960 two thousand and twelve. They spun off from a research 0:21:25.000 --> 0:21:27.760 group at the University of Washington UH. They developed a 0:21:27.840 --> 0:21:32.200 chip that actually mimics the blood brain barrier, which is 0:21:32.240 --> 0:21:34.760 pretty awesome. That's one of those things in medicine that 0:21:35.200 --> 0:21:37.760 fascinates and confuses me every time I hear about it. 0:21:37.760 --> 0:21:40.960 It's one of those, uh difficult issues, is how do 0:21:41.000 --> 0:21:44.119 you get things that either do not breach the blood 0:21:44.119 --> 0:21:47.280 brain barrier or do breach the blood brain barrier. So 0:21:48.200 --> 0:21:51.200 with the startup, I think we're gonna see some partnerships 0:21:51.240 --> 0:21:55.680 between Emulat Incorporated and other companies to really test these 0:21:55.680 --> 0:21:59.159 out and check to make sure that these actually do 0:21:59.240 --> 0:22:03.160 work as an analog um and it's interesting. They've even 0:22:03.240 --> 0:22:06.400 come up with a a version where they can hook 0:22:06.520 --> 0:22:09.679 up the different organs on a chip together in a 0:22:09.760 --> 0:22:13.879 system to simulate an entire human body. So essentially you 0:22:13.920 --> 0:22:18.120 have all these different chips operating as the different organs, uh, 0:22:18.119 --> 0:22:22.400 And that way you can check whole body effects. Yeah. 0:22:22.440 --> 0:22:24.280 So if you again, if you have that drug to 0:22:24.520 --> 0:22:26.840 treat the liver and you want to make sure it's 0:22:26.840 --> 0:22:29.080 not going to put too much stress on some other organ, 0:22:29.320 --> 0:22:32.600 you could introduce it and this will behave as if 0:22:32.640 --> 0:22:36.560 it were a human in miniature in a way. I mean, 0:22:36.600 --> 0:22:39.680 we're talking about teeny tiny elements that are replicating the 0:22:39.720 --> 0:22:44.480 basic functions of the organs that they represent. Yeah, it's 0:22:44.520 --> 0:22:47.600 it's really really mind blowing to think that such a 0:22:47.640 --> 0:22:53.000 tiny sample of cells could be representative of an entire 0:22:53.160 --> 0:22:56.719 organ and its functions. But it is. That's that's at 0:22:56.800 --> 0:23:00.840 least the pitch will find out. Yeah, and you know what, 0:23:00.960 --> 0:23:04.320 while we're we mentioned cost earlier, and right now, this 0:23:04.400 --> 0:23:08.240 sounds like it would not be cheaper. Probably then the 0:23:08.280 --> 0:23:11.560 goal is that by using just very tiny amounts of 0:23:11.680 --> 0:23:16.080 cells and having a streamlined production method, you could actually 0:23:16.080 --> 0:23:18.280 produce a whole bunch of these with just a tiny 0:23:18.320 --> 0:23:22.160