0:00:00.843,0:00:02.888 I'd like to show you a video of some of the models 0:00:02.888,0:00:04.477 I work with. 0:00:04.477,0:00:08.015 They're all the perfect size, and they don't have an ounce of fat. 0:00:08.015,0:00:10.553 Did I mention they're gorgeous? 0:00:10.553,0:00:13.683 And they're scientific models? (Laughs) 0:00:13.683,0:00:16.026 As you might have guessed, I'm a tissue engineer, 0:00:16.026,0:00:18.475 and this is a video of some of the beating heart 0:00:18.475,0:00:20.691 that I've engineered in the lab. 0:00:20.691,0:00:22.573 And one day we hope that these tissues 0:00:22.573,0:00:25.517 can serve as replacement parts for the human body. 0:00:25.517,0:00:27.797 But what I'm going to tell you about today 0:00:27.797,0:00:32.244 is how these tissues make awesome models. 0:00:32.244,0:00:34.971 Well, let's think about the drug screening process for a moment. 0:00:34.971,0:00:37.949 You go from drug formulation, lab testing, animal testing, 0:00:37.949,0:00:40.452 and then clinical trials, which you might call human testing, 0:00:40.452,0:00:42.717 before the drugs get to market. 0:00:42.717,0:00:45.860 It costs a lot of money, a lot of time, 0:00:45.860,0:00:48.670 and sometimes, even when a drug hits the market, 0:00:48.670,0:00:52.605 it acts in an unpredictable way and actually hurts people. 0:00:52.605,0:00:56.692 And the later it fails, the worse the consequences. 0:00:56.692,0:01:00.876 It all boils down to two issues. One, humans are not rats, 0:01:00.876,0:01:04.964 and two, despite our incredible similarities to one another, 0:01:04.964,0:01:07.405 actually those tiny differences between you and I 0:01:07.405,0:01:09.914 have huge impacts with how we metabolize drugs 0:01:09.914,0:01:11.783 and how those drugs affect us. 0:01:11.783,0:01:14.615 So what if we had better models in the lab 0:01:14.615,0:01:17.885 that could not only mimic us better than rats 0:01:17.885,0:01:21.805 but also reflect our diversity? 0:01:21.805,0:01:25.732 Let's see how we can do it with tissue engineering. 0:01:25.732,0:01:28.261 One of the key technologies that's really important 0:01:28.261,0:01:31.453 is what's called induced pluripotent stem cells. 0:01:31.453,0:01:33.971 They were developed in Japan pretty recently. 0:01:33.971,0:01:36.418 Okay, induced pluripotent stem cells. 0:01:36.418,0:01:38.531 They're a lot like embryonic stem cells 0:01:38.531,0:01:40.748 except without the controversy. 0:01:40.748,0:01:43.647 We induce cells, okay, say, skin cells, 0:01:43.647,0:01:46.154 by adding a few genes to them, culturing them, 0:01:46.154,0:01:47.775 and then harvesting them. 0:01:47.775,0:01:50.482 So they're skin cells that can be tricked, 0:01:50.482,0:01:53.266 kind of like cellular amnesia, into an embryonic state. 0:01:53.266,0:01:55.978 So without the controversy, that's cool thing number one. 0:01:55.978,0:01:58.527 Cool thing number two, you can grow any type of tissue 0:01:58.527,0:02:01.082 out of them: brain, heart, liver, you get the picture, 0:02:01.082,0:02:03.605 but out of your cells. 0:02:03.605,0:02:07.170 So we can make a model of your heart, your brain 0:02:07.170,0:02:09.802 on a chip. 0:02:09.802,0:02:12.658 Generating tissues of predictable density and behavior 0:02:12.658,0:02:15.490 is the second piece, and will be really key towards 0:02:15.490,0:02:18.162 getting these models to be adopted for drug discovery. 0:02:18.162,0:02:21.274 And this is a schematic of a bioreactor we're developing in our lab 0:02:21.274,0:02:24.722 to help engineer tissues in a more modular, scalable way. 0:02:24.722,0:02:28.121 Going forward, imagine a massively parallel version of this 0:02:28.121,0:02:30.458 with thousands of pieces of human tissue. 0:02:30.458,0:02:34.506 It would be like having a clinical trial on a chip. 0:02:34.506,0:02:38.301 But another thing about these induced pluripotent stem cells 0:02:38.301,0:02:40.850 is that if we take some skin cells, let's say, 0:02:40.850,0:02:43.026 from people with a genetic disease 0:02:43.026,0:02:45.282 and we engineer tissues out of them, 0:02:45.282,0:02:47.250 we can actually use tissue-engineering techniques 0:02:47.250,0:02:50.651 to generate models of those diseases in the lab. 0:02:50.651,0:02:54.235 Here's an example from Kevin Eggan's lab at Harvard. 0:02:54.235,0:02:56.525 He generated neurons 0:02:56.525,0:02:59.240 from these induced pluripotent stem cells 0:02:59.240,0:03:01.869 from patients who have Lou Gehrig's Disease, 0:03:01.869,0:03:04.312 and he differentiated them into neurons, and what's amazing 0:03:04.312,0:03:07.464 is that these neurons also show symptoms of the disease. 0:03:07.464,0:03:09.563 So with disease models like these, we can fight back 0:03:09.563,0:03:12.145 faster than ever before and understand the disease better 0:03:12.145,0:03:16.108 than ever before, and maybe discover drugs even faster. 0:03:16.108,0:03:19.488 This is another example of patient-specific stem cells 0:03:19.488,0:03:23.497 that were engineered from someone with retinitis pigmentosa. 0:03:23.497,0:03:25.251 This is a degeneration of the retina. 0:03:25.251,0:03:28.008 It's a disease that runs in my family, and we really hope 0:03:28.008,0:03:30.232 that cells like these will help us find a cure. 0:03:30.232,0:03:33.040 So some people think that these models sound well and good, 0:03:33.040,0:03:36.481 but ask, "Well, are these really as good as the rat?" 0:03:36.481,0:03:39.469 The rat is an entire organism, after all, 0:03:39.469,0:03:41.175 with interacting networks of organs. 0:03:41.175,0:03:45.096 A drug for the heart can get metabolized in the liver, 0:03:45.096,0:03:47.936 and some of the byproducts may be stored in the fat. 0:03:47.936,0:03:52.463 Don't you miss all that with these tissue-engineered models? 0:03:52.463,0:03:54.577 Well, this is another trend in the field. 0:03:54.577,0:03:57.444 By combining tissue engineering techniques with microfluidics, 0:03:57.444,0:03:59.608 the field is actually evolving towards just that, 0:03:59.608,0:04:02.114 a model of the entire ecosystem of the body, 0:04:02.114,0:04:04.514 complete with multiple organ systems to be able to test 0:04:04.514,0:04:06.117 how a drug you might take for your blood pressure 0:04:06.117,0:04:09.384 might affect your liver or an antidepressant might affect your heart. 0:04:09.384,0:04:13.456 These systems are really hard to build, but we're just starting to be able to get there, 0:04:13.456,0:04:16.760 and so, watch out. 0:04:16.760,0:04:19.392 But that's not even all of it, because once a drug is approved, 0:04:19.392,0:04:23.074 tissue engineering techniques can actually help us develop more personalized treatments. 0:04:23.074,0:04:26.816 This is an example that you might care about someday, 0:04:26.816,0:04:28.936 and I hope you never do, 0:04:28.936,0:04:31.456 because imagine if you ever get that call 0:04:31.456,0:04:34.664 that gives you that bad news that you might have cancer. 0:04:34.664,0:04:37.200 Wouldn't you rather test to see if those cancer drugs 0:04:37.200,0:04:39.960 you're going to take are going to work on your cancer? 0:04:39.960,0:04:42.382 This is an example from Karen Burg's lab, where they're 0:04:42.382,0:04:45.288 using inkjet technologies to print breast cancer cells 0:04:45.288,0:04:47.759 and study its progressions and treatments. 0:04:47.759,0:04:50.312 And some of our colleagues at Tufts are mixing models 0:04:50.312,0:04:53.400 like these with tissue-engineered bone to see how cancer 0:04:53.400,0:04:56.120 might spread from one part of the body to the next, 0:04:56.120,0:04:58.504 and you can imagine those kinds of multi-tissue chips 0:04:58.504,0:05:01.489 to be the next generation of these kinds of studies. 0:05:01.489,0:05:03.911 And so thinking about the models that we've just discussed, 0:05:03.911,0:05:05.824 you can see, going forward, that tissue engineering 0:05:05.824,0:05:08.280 is actually poised to help revolutionize drug screening 0:05:08.280,0:05:11.058 at every single step of the path: 0:05:11.058,0:05:13.632 disease models making for better drug formulations, 0:05:13.632,0:05:17.503 massively parallel human tissue models helping to revolutionize lab testing, 0:05:17.503,0:05:21.728 reduce animal testing and human testing in clinical trials, 0:05:21.728,0:05:23.420 and individualized therapies that disrupt 0:05:23.420,0:05:27.008 what we even consider to be a market at all. 0:05:27.008,0:05:29.552 Essentially, we're dramatically speeding up that feedback 0:05:29.552,0:05:31.875 between developing a molecule and learning about 0:05:31.875,0:05:34.224 how it acts in the human body. 0:05:34.224,0:05:36.552 Our process for doing this is essentially transforming 0:05:36.552,0:05:41.413 biotechnology and pharmacology into an information technology, 0:05:41.413,0:05:44.392 helping us discover and evaluate drugs faster, 0:05:44.392,0:05:47.608 more cheaply and more effectively. 0:05:47.608,0:05:51.688 It gives new meaning to models against animal testing, doesn't it? 0:05:51.688,0:05:58.503 Thank you. (Applause)