WEBVTT 00:00:00.843 --> 00:00:02.888 I'd like to show you a video of some of the models 00:00:02.888 --> 00:00:04.477 I work with. 00:00:04.477 --> 00:00:08.015 They're all the perfect size, and they don't have an ounce of fat. 00:00:08.015 --> 00:00:10.553 Did I mention they're gorgeous? 00:00:10.553 --> 00:00:13.683 And they're scientific models? (Laughs) NOTE Paragraph 00:00:13.683 --> 00:00:16.026 As you might have guessed, I'm a tissue engineer, 00:00:16.026 --> 00:00:18.475 and this is a video of some of the beating heart 00:00:18.475 --> 00:00:20.691 that I've engineered in the lab. 00:00:20.691 --> 00:00:22.573 And one day we hope that these tissues 00:00:22.573 --> 00:00:25.517 can serve as replacement parts for the human body. 00:00:25.517 --> 00:00:27.797 But what I'm going to tell you about today 00:00:27.797 --> 00:00:32.244 is how these tissues make awesome models. NOTE Paragraph 00:00:32.244 --> 00:00:34.971 Well, let's think about the drug screening process for a moment. 00:00:34.971 --> 00:00:37.949 You go from drug formulation, lab testing, animal testing, 00:00:37.949 --> 00:00:40.452 and then clinical trials, which you might call human testing, 00:00:40.452 --> 00:00:42.717 before the drugs get to market. 00:00:42.717 --> 00:00:45.860 It costs a lot of money, a lot of time, 00:00:45.860 --> 00:00:48.670 and sometimes, even when a drug hits the market, 00:00:48.670 --> 00:00:52.605 it acts in an unpredictable way and actually hurts people. 00:00:52.605 --> 00:00:56.692 And the later it fails, the worse the consequences. NOTE Paragraph 00:00:56.692 --> 00:01:00.876 It all boils down to two issues. One, humans are not rats, 00:01:00.876 --> 00:01:04.964 and two, despite our incredible similarities to one another, 00:01:04.964 --> 00:01:07.405 actually those tiny differences between you and I 00:01:07.405 --> 00:01:09.914 have huge impacts with how we metabolize drugs 00:01:09.914 --> 00:01:11.783 and how those drugs affect us. NOTE Paragraph 00:01:11.783 --> 00:01:14.615 So what if we had better models in the lab 00:01:14.615 --> 00:01:17.885 that could not only mimic us better than rats 00:01:17.885 --> 00:01:21.805 but also reflect our diversity? 00:01:21.805 --> 00:01:25.732 Let's see how we can do it with tissue engineering. NOTE Paragraph 00:01:25.732 --> 00:01:28.261 One of the key technologies that's really important 00:01:28.261 --> 00:01:31.453 is what's called induced pluripotent stem cells. 00:01:31.453 --> 00:01:33.971 They were developed in Japan pretty recently. 00:01:33.971 --> 00:01:36.418 Okay, induced pluripotent stem cells. 00:01:36.418 --> 00:01:38.531 They're a lot like embryonic stem cells 00:01:38.531 --> 00:01:40.748 except without the controversy. 00:01:40.748 --> 00:01:43.647 We induce cells, okay, say, skin cells, 00:01:43.647 --> 00:01:46.154 by adding a few genes to them, culturing them, 00:01:46.154 --> 00:01:47.775 and then harvesting them. 00:01:47.775 --> 00:01:50.482 So they're skin cells that can be tricked, 00:01:50.482 --> 00:01:53.266 kind of like cellular amnesia, into an embryonic state. 00:01:53.266 --> 00:01:55.978 So without the controversy, that's cool thing number one. 00:01:55.978 --> 00:01:58.527 Cool thing number two, you can grow any type of tissue 00:01:58.527 --> 00:02:01.082 out of them: brain, heart, liver, you get the picture, 00:02:01.082 --> 00:02:03.605 but out of your cells. 00:02:03.605 --> 00:02:07.170 So we can make a model of your heart, your brain 00:02:07.170 --> 00:02:09.802 on a chip. NOTE Paragraph 00:02:09.802 --> 00:02:12.658 Generating tissues of predictable density and behavior 00:02:12.658 --> 00:02:15.490 is the second piece, and will be really key towards 00:02:15.490 --> 00:02:18.162 getting these models to be adopted for drug discovery. 00:02:18.162 --> 00:02:21.274 And this is a schematic of a bioreactor we're developing in our lab 00:02:21.274 --> 00:02:24.722 to help engineer tissues in a more modular, scalable way. 00:02:24.722 --> 00:02:28.121 Going forward, imagine a massively parallel version of this 00:02:28.121 --> 00:02:30.458 with thousands of pieces of human tissue. 00:02:30.458 --> 00:02:34.506 It would be like having a clinical trial on a chip. NOTE Paragraph 00:02:34.506 --> 00:02:38.301 But another thing about these induced pluripotent stem cells 00:02:38.301 --> 00:02:40.850 is that if we take some skin cells, let's say, 00:02:40.850 --> 00:02:43.026 from people with a genetic disease 00:02:43.026 --> 00:02:45.282 and we engineer tissues out of them, 00:02:45.282 --> 00:02:47.250 we can actually use tissue-engineering techniques 00:02:47.250 --> 00:02:50.651 to generate models of those diseases in the lab. 00:02:50.651 --> 00:02:54.235 Here's an example from Kevin Eggan's lab at Harvard. 00:02:54.235 --> 00:02:56.525 He generated neurons 00:02:56.525 --> 00:02:59.240 from these induced pluripotent stem cells 00:02:59.240 --> 00:03:01.869 from patients who have Lou Gehrig's Disease, 00:03:01.869 --> 00:03:04.312 and he differentiated them into neurons, and what's amazing 00:03:04.312 --> 00:03:07.464 is that these neurons also show symptoms of the disease. 00:03:07.464 --> 00:03:09.563 So with disease models like these, we can fight back 00:03:09.563 --> 00:03:12.145 faster than ever before and understand the disease better 00:03:12.145 --> 00:03:16.108 than ever before, and maybe discover drugs even faster. 00:03:16.108 --> 00:03:19.488 This is another example of patient-specific stem cells 00:03:19.488 --> 00:03:23.497 that were engineered from someone with retinitis pigmentosa. 00:03:23.497 --> 00:03:25.251 This is a degeneration of the retina. 00:03:25.251 --> 00:03:28.008 It's a disease that runs in my family, and we really hope 00:03:28.008 --> 00:03:30.232 that cells like these will help us find a cure. NOTE Paragraph 00:03:30.232 --> 00:03:33.040 So some people think that these models sound well and good, 00:03:33.040 --> 00:03:36.481 but ask, "Well, are these really as good as the rat?" 00:03:36.481 --> 00:03:39.469 The rat is an entire organism, after all, 00:03:39.469 --> 00:03:41.175 with interacting networks of organs. 00:03:41.175 --> 00:03:45.096 A drug for the heart can get metabolized in the liver, 00:03:45.096 --> 00:03:47.936 and some of the byproducts may be stored in the fat. 00:03:47.936 --> 00:03:52.463 Don't you miss all that with these tissue-engineered models? 00:03:52.463 --> 00:03:54.577 Well, this is another trend in the field. 00:03:54.577 --> 00:03:57.444 By combining tissue engineering techniques with microfluidics, 00:03:57.444 --> 00:03:59.608 the field is actually evolving towards just that, 00:03:59.608 --> 00:04:02.114 a model of the entire ecosystem of the body, 00:04:02.114 --> 00:04:04.514 complete with multiple organ systems to be able to test 00:04:04.514 --> 00:04:06.117 how a drug you might take for your blood pressure 00:04:06.117 --> 00:04:09.384 might affect your liver or an antidepressant might affect your heart. 00:04:09.384 --> 00:04:13.456 These systems are really hard to build, but we're just starting to be able to get there, 00:04:13.456 --> 00:04:16.760 and so, watch out. NOTE Paragraph 00:04:16.760 --> 00:04:19.392 But that's not even all of it, because once a drug is approved, 00:04:19.392 --> 00:04:23.074 tissue engineering techniques can actually help us develop more personalized treatments. 00:04:23.074 --> 00:04:26.816 This is an example that you might care about someday, 00:04:26.816 --> 00:04:28.936 and I hope you never do, 00:04:28.936 --> 00:04:31.456 because imagine if you ever get that call 00:04:31.456 --> 00:04:34.664 that gives you that bad news that you might have cancer. 00:04:34.664 --> 00:04:37.200 Wouldn't you rather test to see if those cancer drugs 00:04:37.200 --> 00:04:39.960 you're going to take are going to work on your cancer? 00:04:39.960 --> 00:04:42.382 This is an example from Karen Burg's lab, where they're 00:04:42.382 --> 00:04:45.288 using inkjet technologies to print breast cancer cells 00:04:45.288 --> 00:04:47.759 and study its progressions and treatments. 00:04:47.759 --> 00:04:50.312 And some of our colleagues at Tufts are mixing models 00:04:50.312 --> 00:04:53.400 like these with tissue-engineered bone to see how cancer 00:04:53.400 --> 00:04:56.120 might spread from one part of the body to the next, 00:04:56.120 --> 00:04:58.504 and you can imagine those kinds of multi-tissue chips 00:04:58.504 --> 00:05:01.489 to be the next generation of these kinds of studies. NOTE Paragraph 00:05:01.489 --> 00:05:03.911 And so thinking about the models that we've just discussed, 00:05:03.911 --> 00:05:05.824 you can see, going forward, that tissue engineering 00:05:05.824 --> 00:05:08.280 is actually poised to help revolutionize drug screening 00:05:08.280 --> 00:05:11.058 at every single step of the path: 00:05:11.058 --> 00:05:13.632 disease models making for better drug formulations, 00:05:13.632 --> 00:05:17.503 massively parallel human tissue models helping to revolutionize lab testing, 00:05:17.503 --> 00:05:21.728 reduce animal testing and human testing in clinical trials, 00:05:21.728 --> 00:05:23.420 and individualized therapies that disrupt 00:05:23.420 --> 00:05:27.008 what we even consider to be a market at all. 00:05:27.008 --> 00:05:29.552 Essentially, we're dramatically speeding up that feedback 00:05:29.552 --> 00:05:31.875 between developing a molecule and learning about 00:05:31.875 --> 00:05:34.224 how it acts in the human body. 00:05:34.224 --> 00:05:36.552 Our process for doing this is essentially transforming 00:05:36.552 --> 00:05:41.413 biotechnology and pharmacology into an information technology, 00:05:41.413 --> 00:05:44.392 helping us discover and evaluate drugs faster, 00:05:44.392 --> 00:05:47.608 more cheaply and more effectively. 00:05:47.608 --> 00:05:51.688 It gives new meaning to models against animal testing, doesn't it? 00:05:51.688 --> 00:05:58.503 Thank you. (Applause)