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Dialogue: 0,0:00:00.84,0:00:02.89,Default,,0000,0000,0000,,I'd like to show you a video of some of the models
Dialogue: 0,0:00:02.89,0:00:04.48,Default,,0000,0000,0000,,I work with.
Dialogue: 0,0:00:04.48,0:00:08.02,Default,,0000,0000,0000,,They're all the perfect size, and they don't have an ounce of fat.
Dialogue: 0,0:00:08.02,0:00:10.55,Default,,0000,0000,0000,,Did I mention they're gorgeous?
Dialogue: 0,0:00:10.55,0:00:13.68,Default,,0000,0000,0000,,And they're scientific models? (Laughs)
Dialogue: 0,0:00:13.68,0:00:16.03,Default,,0000,0000,0000,,As you might have guessed, I'm a tissue engineer,
Dialogue: 0,0:00:16.03,0:00:18.48,Default,,0000,0000,0000,,and this is a video of some of the beating heart
Dialogue: 0,0:00:18.48,0:00:20.69,Default,,0000,0000,0000,,that I've engineered in the lab.
Dialogue: 0,0:00:20.69,0:00:22.57,Default,,0000,0000,0000,,And one day we hope that these tissues
Dialogue: 0,0:00:22.57,0:00:25.52,Default,,0000,0000,0000,,can serve as replacement parts for the human body.
Dialogue: 0,0:00:25.52,0:00:27.80,Default,,0000,0000,0000,,But what I'm going to tell you about today
Dialogue: 0,0:00:27.80,0:00:32.24,Default,,0000,0000,0000,,is how these tissues make awesome models.
Dialogue: 0,0:00:32.24,0:00:34.97,Default,,0000,0000,0000,,Well, let's think about the drug screening process for a moment.
Dialogue: 0,0:00:34.97,0:00:37.95,Default,,0000,0000,0000,,You go from drug formulation, lab testing, animal testing,
Dialogue: 0,0:00:37.95,0:00:40.45,Default,,0000,0000,0000,,and then clinical trials, which you might call human testing,
Dialogue: 0,0:00:40.45,0:00:42.72,Default,,0000,0000,0000,,before the drugs get to market.
Dialogue: 0,0:00:42.72,0:00:45.86,Default,,0000,0000,0000,,It costs a lot of money, a lot of time,
Dialogue: 0,0:00:45.86,0:00:48.67,Default,,0000,0000,0000,,and sometimes, even when a drug hits the market,
Dialogue: 0,0:00:48.67,0:00:52.60,Default,,0000,0000,0000,,it acts in an unpredictable way and actually hurts people.
Dialogue: 0,0:00:52.60,0:00:56.69,Default,,0000,0000,0000,,And the later it fails, the worse the consequences.
Dialogue: 0,0:00:56.69,0:01:00.88,Default,,0000,0000,0000,,It all boils down to two issues. One, humans are not rats,
Dialogue: 0,0:01:00.88,0:01:04.96,Default,,0000,0000,0000,,and two, despite our incredible similarities to one another,
Dialogue: 0,0:01:04.96,0:01:07.40,Default,,0000,0000,0000,,actually those tiny differences between you and I
Dialogue: 0,0:01:07.40,0:01:09.91,Default,,0000,0000,0000,,have huge impacts with how we metabolize drugs
Dialogue: 0,0:01:09.91,0:01:11.78,Default,,0000,0000,0000,,and how those drugs affect us.
Dialogue: 0,0:01:11.78,0:01:14.62,Default,,0000,0000,0000,,So what if we had better models in the lab
Dialogue: 0,0:01:14.62,0:01:17.88,Default,,0000,0000,0000,,that could not only mimic us better than rats
Dialogue: 0,0:01:17.88,0:01:21.80,Default,,0000,0000,0000,,but also reflect our diversity?
Dialogue: 0,0:01:21.80,0:01:25.73,Default,,0000,0000,0000,,Let's see how we can do it with tissue engineering.
Dialogue: 0,0:01:25.73,0:01:28.26,Default,,0000,0000,0000,,One of the key technologies that's really important
Dialogue: 0,0:01:28.26,0:01:31.45,Default,,0000,0000,0000,,is what's called induced pluripotent stem cells.
Dialogue: 0,0:01:31.45,0:01:33.97,Default,,0000,0000,0000,,They were developed in Japan pretty recently.
Dialogue: 0,0:01:33.97,0:01:36.42,Default,,0000,0000,0000,,Okay, induced pluripotent stem cells.
Dialogue: 0,0:01:36.42,0:01:38.53,Default,,0000,0000,0000,,They're a lot like embryonic stem cells
Dialogue: 0,0:01:38.53,0:01:40.75,Default,,0000,0000,0000,,except without the controversy.
Dialogue: 0,0:01:40.75,0:01:43.65,Default,,0000,0000,0000,,We induce cells, okay, say, skin cells,
Dialogue: 0,0:01:43.65,0:01:46.15,Default,,0000,0000,0000,,by adding a few genes to them, culturing them,
Dialogue: 0,0:01:46.15,0:01:47.78,Default,,0000,0000,0000,,and then harvesting them.
Dialogue: 0,0:01:47.78,0:01:50.48,Default,,0000,0000,0000,,So they're skin cells that can be tricked,
Dialogue: 0,0:01:50.48,0:01:53.27,Default,,0000,0000,0000,,kind of like cellular amnesia, into an embryonic state.
Dialogue: 0,0:01:53.27,0:01:55.98,Default,,0000,0000,0000,,So without the controversy, that's cool thing number one.
Dialogue: 0,0:01:55.98,0:01:58.53,Default,,0000,0000,0000,,Cool thing number two, you can grow any type of tissue
Dialogue: 0,0:01:58.53,0:02:01.08,Default,,0000,0000,0000,,out of them: brain, heart, liver, you get the picture,
Dialogue: 0,0:02:01.08,0:02:03.60,Default,,0000,0000,0000,,but out of your cells.
Dialogue: 0,0:02:03.60,0:02:07.17,Default,,0000,0000,0000,,So we can make a model of your heart, your brain
Dialogue: 0,0:02:07.17,0:02:09.80,Default,,0000,0000,0000,,on a chip.
Dialogue: 0,0:02:09.80,0:02:12.66,Default,,0000,0000,0000,,Generating tissues of predictable density and behavior
Dialogue: 0,0:02:12.66,0:02:15.49,Default,,0000,0000,0000,,is the second piece, and will be really key towards
Dialogue: 0,0:02:15.49,0:02:18.16,Default,,0000,0000,0000,,getting these models to be adopted for drug discovery.
Dialogue: 0,0:02:18.16,0:02:21.27,Default,,0000,0000,0000,,And this is a schematic of a bioreactor we're developing in our lab
Dialogue: 0,0:02:21.27,0:02:24.72,Default,,0000,0000,0000,,to help engineer tissues in a more modular, scalable way.
Dialogue: 0,0:02:24.72,0:02:28.12,Default,,0000,0000,0000,,Going forward, imagine a massively parallel version of this
Dialogue: 0,0:02:28.12,0:02:30.46,Default,,0000,0000,0000,,with thousands of pieces of human tissue.
Dialogue: 0,0:02:30.46,0:02:34.51,Default,,0000,0000,0000,,It would be like having a clinical trial on a chip.
Dialogue: 0,0:02:34.51,0:02:38.30,Default,,0000,0000,0000,,But another thing about these induced pluripotent stem cells
Dialogue: 0,0:02:38.30,0:02:40.85,Default,,0000,0000,0000,,is that if we take some skin cells, let's say,
Dialogue: 0,0:02:40.85,0:02:43.03,Default,,0000,0000,0000,,from people with a genetic disease
Dialogue: 0,0:02:43.03,0:02:45.28,Default,,0000,0000,0000,,and we engineer tissues out of them,
Dialogue: 0,0:02:45.28,0:02:47.25,Default,,0000,0000,0000,,we can actually use tissue-engineering techniques
Dialogue: 0,0:02:47.25,0:02:50.65,Default,,0000,0000,0000,,to generate models of those diseases in the lab.
Dialogue: 0,0:02:50.65,0:02:54.24,Default,,0000,0000,0000,,Here's an example from Kevin Eggan's lab at Harvard.
Dialogue: 0,0:02:54.24,0:02:56.52,Default,,0000,0000,0000,,He generated neurons
Dialogue: 0,0:02:56.52,0:02:59.24,Default,,0000,0000,0000,,from these induced pluripotent stem cells
Dialogue: 0,0:02:59.24,0:03:01.87,Default,,0000,0000,0000,,from patients who have Lou Gehrig's Disease,
Dialogue: 0,0:03:01.87,0:03:04.31,Default,,0000,0000,0000,,and he differentiated them into neurons, and what's amazing
Dialogue: 0,0:03:04.31,0:03:07.46,Default,,0000,0000,0000,,is that these neurons also show symptoms of the disease.
Dialogue: 0,0:03:07.46,0:03:09.56,Default,,0000,0000,0000,,So with disease models like these, we can fight back
Dialogue: 0,0:03:09.56,0:03:12.14,Default,,0000,0000,0000,,faster than ever before and understand the disease better
Dialogue: 0,0:03:12.14,0:03:16.11,Default,,0000,0000,0000,,than ever before, and maybe discover drugs even faster.
Dialogue: 0,0:03:16.11,0:03:19.49,Default,,0000,0000,0000,,This is another example of patient-specific stem cells
Dialogue: 0,0:03:19.49,0:03:23.50,Default,,0000,0000,0000,,that were engineered from someone with retinitis pigmentosa.
Dialogue: 0,0:03:23.50,0:03:25.25,Default,,0000,0000,0000,,This is a degeneration of the retina.
Dialogue: 0,0:03:25.25,0:03:28.01,Default,,0000,0000,0000,,It's a disease that runs in my family, and we really hope
Dialogue: 0,0:03:28.01,0:03:30.23,Default,,0000,0000,0000,,that cells like these will help us find a cure.
Dialogue: 0,0:03:30.23,0:03:33.04,Default,,0000,0000,0000,,So some people think that these models sound well and good,
Dialogue: 0,0:03:33.04,0:03:36.48,Default,,0000,0000,0000,,but ask, "Well, are these really as good as the rat?"
Dialogue: 0,0:03:36.48,0:03:39.47,Default,,0000,0000,0000,,The rat is an entire organism, after all,
Dialogue: 0,0:03:39.47,0:03:41.18,Default,,0000,0000,0000,,with interacting networks of organs.
Dialogue: 0,0:03:41.18,0:03:45.10,Default,,0000,0000,0000,,A drug for the heart can get metabolized in the liver,
Dialogue: 0,0:03:45.10,0:03:47.94,Default,,0000,0000,0000,,and some of the byproducts may be stored in the fat.
Dialogue: 0,0:03:47.94,0:03:52.46,Default,,0000,0000,0000,,Don't you miss all that with these tissue-engineered models?
Dialogue: 0,0:03:52.46,0:03:54.58,Default,,0000,0000,0000,,Well, this is another trend in the field.
Dialogue: 0,0:03:54.58,0:03:57.44,Default,,0000,0000,0000,,By combining tissue engineering techniques with microfluidics,
Dialogue: 0,0:03:57.44,0:03:59.61,Default,,0000,0000,0000,,the field is actually evolving towards just that,
Dialogue: 0,0:03:59.61,0:04:02.11,Default,,0000,0000,0000,,a model of the entire ecosystem of the body,
Dialogue: 0,0:04:02.11,0:04:04.51,Default,,0000,0000,0000,,complete with multiple organ systems to be able to test
Dialogue: 0,0:04:04.51,0:04:06.12,Default,,0000,0000,0000,,how a drug you might take for your blood pressure
Dialogue: 0,0:04:06.12,0:04:09.38,Default,,0000,0000,0000,,might affect your liver or an antidepressant might affect your heart.
Dialogue: 0,0:04:09.38,0:04:13.46,Default,,0000,0000,0000,,These systems are really hard to build, but we're just starting to be able to get there,
Dialogue: 0,0:04:13.46,0:04:16.76,Default,,0000,0000,0000,,and so, watch out.
Dialogue: 0,0:04:16.76,0:04:19.39,Default,,0000,0000,0000,,But that's not even all of it, because once a drug is approved,
Dialogue: 0,0:04:19.39,0:04:23.07,Default,,0000,0000,0000,,tissue engineering techniques can actually help us develop more personalized treatments.
Dialogue: 0,0:04:23.07,0:04:26.82,Default,,0000,0000,0000,,This is an example that you might care about someday,
Dialogue: 0,0:04:26.82,0:04:28.94,Default,,0000,0000,0000,,and I hope you never do,
Dialogue: 0,0:04:28.94,0:04:31.46,Default,,0000,0000,0000,,because imagine if you ever get that call
Dialogue: 0,0:04:31.46,0:04:34.66,Default,,0000,0000,0000,,that gives you that bad news that you might have cancer.
Dialogue: 0,0:04:34.66,0:04:37.20,Default,,0000,0000,0000,,Wouldn't you rather test to see if those cancer drugs
Dialogue: 0,0:04:37.20,0:04:39.96,Default,,0000,0000,0000,,you're going to take are going to work on your cancer?
Dialogue: 0,0:04:39.96,0:04:42.38,Default,,0000,0000,0000,,This is an example from Karen Burg's lab, where they're
Dialogue: 0,0:04:42.38,0:04:45.29,Default,,0000,0000,0000,,using inkjet technologies to print breast cancer cells
Dialogue: 0,0:04:45.29,0:04:47.76,Default,,0000,0000,0000,,and study its progressions and treatments.
Dialogue: 0,0:04:47.76,0:04:50.31,Default,,0000,0000,0000,,And some of our colleagues at Tufts are mixing models
Dialogue: 0,0:04:50.31,0:04:53.40,Default,,0000,0000,0000,,like these with tissue-engineered bone to see how cancer
Dialogue: 0,0:04:53.40,0:04:56.12,Default,,0000,0000,0000,,might spread from one part of the body to the next,
Dialogue: 0,0:04:56.12,0:04:58.50,Default,,0000,0000,0000,,and you can imagine those kinds of multi-tissue chips
Dialogue: 0,0:04:58.50,0:05:01.49,Default,,0000,0000,0000,,to be the next generation of these kinds of studies.
Dialogue: 0,0:05:01.49,0:05:03.91,Default,,0000,0000,0000,,And so thinking about the models that we've just discussed,
Dialogue: 0,0:05:03.91,0:05:05.82,Default,,0000,0000,0000,,you can see, going forward, that tissue engineering
Dialogue: 0,0:05:05.82,0:05:08.28,Default,,0000,0000,0000,,is actually poised to help revolutionize drug screening
Dialogue: 0,0:05:08.28,0:05:11.06,Default,,0000,0000,0000,,at every single step of the path:
Dialogue: 0,0:05:11.06,0:05:13.63,Default,,0000,0000,0000,,disease models making for better drug formulations,
Dialogue: 0,0:05:13.63,0:05:17.50,Default,,0000,0000,0000,,massively parallel human tissue models helping to revolutionize lab testing,
Dialogue: 0,0:05:17.50,0:05:21.73,Default,,0000,0000,0000,,reduce animal testing and human testing in clinical trials,
Dialogue: 0,0:05:21.73,0:05:23.42,Default,,0000,0000,0000,,and individualized therapies that disrupt
Dialogue: 0,0:05:23.42,0:05:27.01,Default,,0000,0000,0000,,what we even consider to be a market at all.
Dialogue: 0,0:05:27.01,0:05:29.55,Default,,0000,0000,0000,,Essentially, we're dramatically speeding up that feedback
Dialogue: 0,0:05:29.55,0:05:31.88,Default,,0000,0000,0000,,between developing a molecule and learning about
Dialogue: 0,0:05:31.88,0:05:34.22,Default,,0000,0000,0000,,how it acts in the human body.
Dialogue: 0,0:05:34.22,0:05:36.55,Default,,0000,0000,0000,,Our process for doing this is essentially transforming
Dialogue: 0,0:05:36.55,0:05:41.41,Default,,0000,0000,0000,,biotechnology and pharmacology into an information technology,
Dialogue: 0,0:05:41.41,0:05:44.39,Default,,0000,0000,0000,,helping us discover and evaluate drugs faster,
Dialogue: 0,0:05:44.39,0:05:47.61,Default,,0000,0000,0000,,more cheaply and more effectively.
Dialogue: 0,0:05:47.61,0:05:51.69,Default,,0000,0000,0000,,It gives new meaning to models against animal testing, doesn't it?
Dialogue: 0,0:05:51.69,0:05:58.50,Default,,0000,0000,0000,,Thank you. (Applause)