[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.72,0:00:02.90,Default,,0000,0000,0000,,So let me ask for a show of hands.
Dialogue: 0,0:00:02.90,0:00:07.09,Default,,0000,0000,0000,,How many people here are over the age of 48?
Dialogue: 0,0:00:07.09,0:00:09.97,Default,,0000,0000,0000,,Well, there do seem to be a few.
Dialogue: 0,0:00:09.97,0:00:12.15,Default,,0000,0000,0000,,Well, congratulations,
Dialogue: 0,0:00:12.15,0:00:16.02,Default,,0000,0000,0000,,because if you look at this particular slide of U.S. life expectancy,
Dialogue: 0,0:00:16.02,0:00:19.12,Default,,0000,0000,0000,,you are now in excess of the average life span
Dialogue: 0,0:00:19.12,0:00:21.90,Default,,0000,0000,0000,,of somebody who was born in 1900.
Dialogue: 0,0:00:21.90,0:00:25.44,Default,,0000,0000,0000,,But look what happened in the course of that century.
Dialogue: 0,0:00:25.44,0:00:27.10,Default,,0000,0000,0000,,If you follow that curve,
Dialogue: 0,0:00:27.10,0:00:29.71,Default,,0000,0000,0000,,you'll see that it starts way down there.
Dialogue: 0,0:00:29.71,0:00:32.18,Default,,0000,0000,0000,,There's that dip there for the 1918 flu.
Dialogue: 0,0:00:32.18,0:00:34.60,Default,,0000,0000,0000,,And here we are at 2010,
Dialogue: 0,0:00:34.60,0:00:37.66,Default,,0000,0000,0000,,average life expectancy of a child born today, age 79,
Dialogue: 0,0:00:37.66,0:00:39.56,Default,,0000,0000,0000,,and we are not done yet.
Dialogue: 0,0:00:39.56,0:00:40.89,Default,,0000,0000,0000,,Now, that's the good news.
Dialogue: 0,0:00:40.89,0:00:42.73,Default,,0000,0000,0000,,But there's still a lot of work to do.
Dialogue: 0,0:00:42.73,0:00:44.36,Default,,0000,0000,0000,,So, for instance, if you ask,
Dialogue: 0,0:00:44.36,0:00:47.09,Default,,0000,0000,0000,,how many diseases do we now know
Dialogue: 0,0:00:47.09,0:00:49.15,Default,,0000,0000,0000,,the exact molecular basis?
Dialogue: 0,0:00:49.15,0:00:52.71,Default,,0000,0000,0000,,Turns out it's about 4,000, which is pretty amazing,
Dialogue: 0,0:00:52.71,0:00:54.94,Default,,0000,0000,0000,,because most of those molecular discoveries
Dialogue: 0,0:00:54.94,0:00:57.61,Default,,0000,0000,0000,,have just happened in the last little while.
Dialogue: 0,0:00:57.61,0:01:00.90,Default,,0000,0000,0000,,It's exciting to see that in terms of what we've learned,
Dialogue: 0,0:01:00.90,0:01:03.01,Default,,0000,0000,0000,,but how many of those 4,000 diseases
Dialogue: 0,0:01:03.01,0:01:05.36,Default,,0000,0000,0000,,now have treatments available?
Dialogue: 0,0:01:05.36,0:01:07.25,Default,,0000,0000,0000,,Only about 250.
Dialogue: 0,0:01:07.25,0:01:10.01,Default,,0000,0000,0000,,So we have this huge challenge, this huge gap.
Dialogue: 0,0:01:10.01,0:01:12.59,Default,,0000,0000,0000,,You would think this wouldn't be too hard,
Dialogue: 0,0:01:12.59,0:01:14.11,Default,,0000,0000,0000,,that we would simply have the ability
Dialogue: 0,0:01:14.11,0:01:17.14,Default,,0000,0000,0000,,to take this fundamental information that we're learning
Dialogue: 0,0:01:17.14,0:01:20.28,Default,,0000,0000,0000,,about how it is that basic biology teaches us
Dialogue: 0,0:01:20.28,0:01:22.18,Default,,0000,0000,0000,,about the causes of disease
Dialogue: 0,0:01:22.18,0:01:25.21,Default,,0000,0000,0000,,and build a bridge across this yawning gap
Dialogue: 0,0:01:25.21,0:01:27.59,Default,,0000,0000,0000,,between what we've learned about basic science
Dialogue: 0,0:01:27.59,0:01:29.09,Default,,0000,0000,0000,,and its application,
Dialogue: 0,0:01:29.09,0:01:32.34,Default,,0000,0000,0000,,a bridge that would look maybe something like this,
Dialogue: 0,0:01:32.34,0:01:35.96,Default,,0000,0000,0000,,where you'd have to put together a nice shiny way
Dialogue: 0,0:01:35.96,0:01:38.92,Default,,0000,0000,0000,,to get from one side to the other.
Dialogue: 0,0:01:38.92,0:01:41.52,Default,,0000,0000,0000,,Well, wouldn't it be nice if it was that easy?
Dialogue: 0,0:01:41.52,0:01:43.67,Default,,0000,0000,0000,,Unfortunately, it's not.
Dialogue: 0,0:01:43.67,0:01:46.26,Default,,0000,0000,0000,,In reality, trying to go from fundamental knowledge
Dialogue: 0,0:01:46.26,0:01:48.92,Default,,0000,0000,0000,,to its application is more like this.
Dialogue: 0,0:01:48.92,0:01:50.84,Default,,0000,0000,0000,,There are no shiny bridges.
Dialogue: 0,0:01:50.84,0:01:52.49,Default,,0000,0000,0000,,You sort of place your bets.
Dialogue: 0,0:01:52.49,0:01:54.45,Default,,0000,0000,0000,,Maybe you've got a swimmer and a rowboat
Dialogue: 0,0:01:54.45,0:01:55.98,Default,,0000,0000,0000,,and a sailboat and a tugboat
Dialogue: 0,0:01:55.98,0:01:57.70,Default,,0000,0000,0000,,and you set them off on their way,
Dialogue: 0,0:01:57.70,0:02:00.37,Default,,0000,0000,0000,,and the rains come and the lightning flashes,
Dialogue: 0,0:02:00.37,0:02:01.88,Default,,0000,0000,0000,,and oh my gosh, there are sharks in the water
Dialogue: 0,0:02:01.88,0:02:03.90,Default,,0000,0000,0000,,and the swimmer gets into trouble,
Dialogue: 0,0:02:03.90,0:02:05.49,Default,,0000,0000,0000,,and, uh oh, the swimmer drowned
Dialogue: 0,0:02:05.49,0:02:08.70,Default,,0000,0000,0000,,and the sailboat capsized,
Dialogue: 0,0:02:08.70,0:02:10.40,Default,,0000,0000,0000,,and that tugboat, well, it hit the rocks,
Dialogue: 0,0:02:10.40,0:02:13.04,Default,,0000,0000,0000,,and maybe if you're lucky, somebody gets across.
Dialogue: 0,0:02:13.04,0:02:15.03,Default,,0000,0000,0000,,Well, what does this really look like?
Dialogue: 0,0:02:15.03,0:02:17.08,Default,,0000,0000,0000,,Well, what is it to make a therapeutic, anyway?
Dialogue: 0,0:02:17.08,0:02:20.08,Default,,0000,0000,0000,,What's a drug? A drug is made up
Dialogue: 0,0:02:20.08,0:02:22.41,Default,,0000,0000,0000,,of a small molecule of hydrogen, carbon,
Dialogue: 0,0:02:22.41,0:02:24.66,Default,,0000,0000,0000,,oxygen, nitrogen, and a few other atoms
Dialogue: 0,0:02:24.66,0:02:26.88,Default,,0000,0000,0000,,all cobbled together in a shape,
Dialogue: 0,0:02:26.88,0:02:29.26,Default,,0000,0000,0000,,and it's those shapes that determine whether, in fact,
Dialogue: 0,0:02:29.26,0:02:32.57,Default,,0000,0000,0000,,that particular drug is going to hit its target.
Dialogue: 0,0:02:32.57,0:02:34.80,Default,,0000,0000,0000,,Is it going to land where it's supposed to?
Dialogue: 0,0:02:34.80,0:02:37.95,Default,,0000,0000,0000,,So look at this picture here -- a lot of shapes dancing around for you.
Dialogue: 0,0:02:37.95,0:02:40.34,Default,,0000,0000,0000,,Now what you need to do, if you're trying to develop
Dialogue: 0,0:02:40.34,0:02:41.80,Default,,0000,0000,0000,,a new treatment for autism
Dialogue: 0,0:02:41.80,0:02:44.01,Default,,0000,0000,0000,,or Alzheimer's disease or cancer
Dialogue: 0,0:02:44.01,0:02:45.81,Default,,0000,0000,0000,,is to find the right shape in that mix
Dialogue: 0,0:02:45.81,0:02:48.72,Default,,0000,0000,0000,,that will ultimately provide benefit and will be safe.
Dialogue: 0,0:02:48.72,0:02:51.89,Default,,0000,0000,0000,,And when you look at what happens to that pipeline,
Dialogue: 0,0:02:51.89,0:02:53.39,Default,,0000,0000,0000,,you start out maybe with thousands,
Dialogue: 0,0:02:53.39,0:02:55.03,Default,,0000,0000,0000,,tens of thousands of compounds.
Dialogue: 0,0:02:55.03,0:02:57.18,Default,,0000,0000,0000,,You weed down through various steps
Dialogue: 0,0:02:57.18,0:02:58.56,Default,,0000,0000,0000,,that cause many of these to fail.
Dialogue: 0,0:02:58.56,0:03:01.90,Default,,0000,0000,0000,,Ultimately, maybe you can run a clinical trial with four or five of these,
Dialogue: 0,0:03:01.90,0:03:04.95,Default,,0000,0000,0000,,and if all goes well, 14 years after you started,
Dialogue: 0,0:03:04.95,0:03:06.96,Default,,0000,0000,0000,,you will get one approval.
Dialogue: 0,0:03:06.96,0:03:08.99,Default,,0000,0000,0000,,And it will cost you upwards of a billion dollars
Dialogue: 0,0:03:08.99,0:03:11.13,Default,,0000,0000,0000,,for that one success.
Dialogue: 0,0:03:11.13,0:03:14.44,Default,,0000,0000,0000,,So we have to look at this pipeline the way an engineer would,
Dialogue: 0,0:03:14.44,0:03:15.64,Default,,0000,0000,0000,,and say, "How can we do better?"
Dialogue: 0,0:03:15.64,0:03:18.32,Default,,0000,0000,0000,,And that's the main theme of what I want to say to you this morning.
Dialogue: 0,0:03:18.32,0:03:20.13,Default,,0000,0000,0000,,How can we make this go faster?
Dialogue: 0,0:03:20.13,0:03:23.20,Default,,0000,0000,0000,,How can we make it more successful?
Dialogue: 0,0:03:23.20,0:03:24.54,Default,,0000,0000,0000,,Well, let me tell you about a few examples
Dialogue: 0,0:03:24.54,0:03:26.80,Default,,0000,0000,0000,,where this has actually worked.
Dialogue: 0,0:03:26.80,0:03:29.75,Default,,0000,0000,0000,,One that has just happened in the last few months
Dialogue: 0,0:03:29.75,0:03:33.46,Default,,0000,0000,0000,,is the successful approval of a drug for cystic fibrosis.
Dialogue: 0,0:03:33.46,0:03:35.11,Default,,0000,0000,0000,,But it's taken a long time to get there.
Dialogue: 0,0:03:35.11,0:03:39.71,Default,,0000,0000,0000,,Cystic fibrosis had its molecular cause discovered in 1989
Dialogue: 0,0:03:39.71,0:03:42.04,Default,,0000,0000,0000,,by my group working with another group in Toronto,
Dialogue: 0,0:03:42.04,0:03:44.18,Default,,0000,0000,0000,,discovering what the mutation was in a particular gene
Dialogue: 0,0:03:44.18,0:03:45.80,Default,,0000,0000,0000,,on chromosome 7.
Dialogue: 0,0:03:45.80,0:03:47.84,Default,,0000,0000,0000,,That picture you see there?
Dialogue: 0,0:03:47.84,0:03:49.94,Default,,0000,0000,0000,,Here it is. That's the same kid.
Dialogue: 0,0:03:49.94,0:03:53.29,Default,,0000,0000,0000,,That's Danny Bessette, 23 years later,
Dialogue: 0,0:03:53.29,0:03:54.57,Default,,0000,0000,0000,,because this is the year,
Dialogue: 0,0:03:54.57,0:03:57.01,Default,,0000,0000,0000,,and it's also the year where Danny got married,
Dialogue: 0,0:03:57.01,0:04:00.06,Default,,0000,0000,0000,,where we have, for the first time, the approval by the FDA
Dialogue: 0,0:04:00.06,0:04:03.80,Default,,0000,0000,0000,,of a drug that precisely targets the defect in cystic fibrosis
Dialogue: 0,0:04:03.80,0:04:05.74,Default,,0000,0000,0000,,based upon all this molecular understanding.
Dialogue: 0,0:04:05.74,0:04:07.16,Default,,0000,0000,0000,,That's the good news.
Dialogue: 0,0:04:07.16,0:04:10.79,Default,,0000,0000,0000,,The bad news is, this drug doesn't actually treat all cases of cystic fibrosis,
Dialogue: 0,0:04:10.79,0:04:13.00,Default,,0000,0000,0000,,and it won't work for Danny, and we're still waiting
Dialogue: 0,0:04:13.00,0:04:15.34,Default,,0000,0000,0000,,for that next generation to help him.
Dialogue: 0,0:04:15.34,0:04:18.53,Default,,0000,0000,0000,,But it took 23 years to get this far. That's too long.
Dialogue: 0,0:04:18.53,0:04:20.22,Default,,0000,0000,0000,,How do we go faster?
Dialogue: 0,0:04:20.22,0:04:22.92,Default,,0000,0000,0000,,Well, one way to go faster is to take advantage of technology,
Dialogue: 0,0:04:22.92,0:04:25.58,Default,,0000,0000,0000,,and a very important technology that we depend on
Dialogue: 0,0:04:25.58,0:04:27.88,Default,,0000,0000,0000,,for all of this is the human genome,
Dialogue: 0,0:04:27.88,0:04:30.47,Default,,0000,0000,0000,,the ability to be able to look at a chromosome,
Dialogue: 0,0:04:30.47,0:04:33.14,Default,,0000,0000,0000,,to unzip it, to pull out all the DNA,
Dialogue: 0,0:04:33.14,0:04:36.09,Default,,0000,0000,0000,,and to be able to then read out the letters in that DNA code,
Dialogue: 0,0:04:36.09,0:04:38.17,Default,,0000,0000,0000,,the A's, C's, G's and T's
Dialogue: 0,0:04:38.17,0:04:41.44,Default,,0000,0000,0000,,that are our instruction book and the instruction book for all living things,
Dialogue: 0,0:04:41.44,0:04:42.96,Default,,0000,0000,0000,,and the cost of doing this,
Dialogue: 0,0:04:42.96,0:04:45.61,Default,,0000,0000,0000,,which used to be in the hundreds of millions of dollars,
Dialogue: 0,0:04:45.61,0:04:47.52,Default,,0000,0000,0000,,has in the course of the last 10 years
Dialogue: 0,0:04:47.52,0:04:49.92,Default,,0000,0000,0000,,fallen faster than Moore's Law, down to the point
Dialogue: 0,0:04:49.92,0:04:53.93,Default,,0000,0000,0000,,where it is less than 10,000 dollars today to have your genome sequenced, or mine,
Dialogue: 0,0:04:53.93,0:04:57.73,Default,,0000,0000,0000,,and we're headed for the $1,000 genome fairly soon.
Dialogue: 0,0:04:57.73,0:04:59.05,Default,,0000,0000,0000,,Well, that's exciting.
Dialogue: 0,0:04:59.05,0:05:02.86,Default,,0000,0000,0000,,How does that play out in terms of application to a disease?
Dialogue: 0,0:05:02.86,0:05:05.14,Default,,0000,0000,0000,,I want to tell you about another disorder.
Dialogue: 0,0:05:05.14,0:05:07.46,Default,,0000,0000,0000,,This one is a disorder which is quite rare.
Dialogue: 0,0:05:07.46,0:05:10.22,Default,,0000,0000,0000,,It's called Hutchinson-Gilford progeria,
Dialogue: 0,0:05:10.22,0:05:13.53,Default,,0000,0000,0000,,and it is the most dramatic form of premature aging.
Dialogue: 0,0:05:13.53,0:05:17.31,Default,,0000,0000,0000,,Only about one in every four million kids has this disease,
Dialogue: 0,0:05:17.31,0:05:20.67,Default,,0000,0000,0000,,and in a simple way, what happens is,
Dialogue: 0,0:05:20.67,0:05:23.37,Default,,0000,0000,0000,,because of a mutation in a particular gene,
Dialogue: 0,0:05:23.37,0:05:26.04,Default,,0000,0000,0000,,a protein is made that's toxic to the cell
Dialogue: 0,0:05:26.04,0:05:28.34,Default,,0000,0000,0000,,and it causes these individuals to age
Dialogue: 0,0:05:28.34,0:05:30.92,Default,,0000,0000,0000,,at about seven times the normal rate.
Dialogue: 0,0:05:30.92,0:05:34.06,Default,,0000,0000,0000,,Let me show you a video of what that does to the cell.
Dialogue: 0,0:05:34.06,0:05:37.20,Default,,0000,0000,0000,,The normal cell, if you looked at it under the microscope,
Dialogue: 0,0:05:37.20,0:05:40.09,Default,,0000,0000,0000,,would have a nucleus sitting in the middle of the cell,
Dialogue: 0,0:05:40.09,0:05:43.97,Default,,0000,0000,0000,,which is nice and round and smooth in its boundaries
Dialogue: 0,0:05:43.97,0:05:45.72,Default,,0000,0000,0000,,and it looks kind of like that.
Dialogue: 0,0:05:45.72,0:05:47.59,Default,,0000,0000,0000,,A progeria cell, on the other hand,
Dialogue: 0,0:05:47.59,0:05:50.69,Default,,0000,0000,0000,,because of this toxic protein called progerin,
Dialogue: 0,0:05:50.69,0:05:52.97,Default,,0000,0000,0000,,has these lumps and bumps in it.
Dialogue: 0,0:05:52.97,0:05:55.99,Default,,0000,0000,0000,,So what we would like to do after discovering this
Dialogue: 0,0:05:55.99,0:05:57.84,Default,,0000,0000,0000,,back in 2003
Dialogue: 0,0:05:57.84,0:06:01.06,Default,,0000,0000,0000,,is to come up with a way to try to correct that.
Dialogue: 0,0:06:01.06,0:06:04.14,Default,,0000,0000,0000,,Well again, by knowing something about the molecular pathways,
Dialogue: 0,0:06:04.14,0:06:06.14,Default,,0000,0000,0000,,it was possible to pick
Dialogue: 0,0:06:06.14,0:06:08.76,Default,,0000,0000,0000,,one of those many, many compounds that might have been useful
Dialogue: 0,0:06:08.76,0:06:10.22,Default,,0000,0000,0000,,and try it out.
Dialogue: 0,0:06:10.22,0:06:12.80,Default,,0000,0000,0000,,In an experiment done in cell culture
Dialogue: 0,0:06:12.80,0:06:14.84,Default,,0000,0000,0000,,and shown here in a cartoon,
Dialogue: 0,0:06:14.84,0:06:17.53,Default,,0000,0000,0000,,if you take that particular compound
Dialogue: 0,0:06:17.53,0:06:20.79,Default,,0000,0000,0000,,and you add it to that cell that has progeria,
Dialogue: 0,0:06:20.79,0:06:23.01,Default,,0000,0000,0000,,and you watch to see what happened,
Dialogue: 0,0:06:23.01,0:06:25.97,Default,,0000,0000,0000,,in just 72 hours, that cell becomes,
Dialogue: 0,0:06:25.97,0:06:28.24,Default,,0000,0000,0000,,for all purposes that we can determine,
Dialogue: 0,0:06:28.24,0:06:30.08,Default,,0000,0000,0000,,almost like a normal cell.
Dialogue: 0,0:06:30.08,0:06:34.42,Default,,0000,0000,0000,,Well that was exciting, but would it actually work in a real human being?
Dialogue: 0,0:06:34.42,0:06:37.81,Default,,0000,0000,0000,,This has led, in the space of only four years
Dialogue: 0,0:06:37.81,0:06:41.31,Default,,0000,0000,0000,,from the time the gene was discovered to the start of a clinical trial,
Dialogue: 0,0:06:41.31,0:06:43.51,Default,,0000,0000,0000,,to a test of that very compound.
Dialogue: 0,0:06:43.51,0:06:45.47,Default,,0000,0000,0000,,And the kids that you see here
Dialogue: 0,0:06:45.47,0:06:48.03,Default,,0000,0000,0000,,all volunteered to be part of this,
Dialogue: 0,0:06:48.03,0:06:49.49,Default,,0000,0000,0000,,28 of them,
Dialogue: 0,0:06:49.49,0:06:52.59,Default,,0000,0000,0000,,and you can see as soon as the picture comes up
Dialogue: 0,0:06:52.59,0:06:55.97,Default,,0000,0000,0000,,that they are in fact a remarkable group of young people
Dialogue: 0,0:06:55.97,0:06:57.39,Default,,0000,0000,0000,,all afflicted by this disease,
Dialogue: 0,0:06:57.39,0:06:59.64,Default,,0000,0000,0000,,all looking quite similar to each other.
Dialogue: 0,0:06:59.64,0:07:01.31,Default,,0000,0000,0000,,And instead of telling you more about it,
Dialogue: 0,0:07:01.31,0:07:05.30,Default,,0000,0000,0000,,I'm going to invite one of them, Sam Berns from Boston,
Dialogue: 0,0:07:05.30,0:07:07.73,Default,,0000,0000,0000,,who's here this morning, to come up on the stage
Dialogue: 0,0:07:07.73,0:07:09.95,Default,,0000,0000,0000,,and tell us about his experience
Dialogue: 0,0:07:09.95,0:07:11.86,Default,,0000,0000,0000,,as a child affected with progeria.
Dialogue: 0,0:07:11.86,0:07:15.92,Default,,0000,0000,0000,,Sam is 15 years old. His parents, Scott Berns and Leslie Gordon,
Dialogue: 0,0:07:15.92,0:07:18.04,Default,,0000,0000,0000,,both physicians, are here with us this morning as well.
Dialogue: 0,0:07:18.04,0:07:20.58,Default,,0000,0000,0000,,Sam, please have a seat.
Dialogue: 0,0:07:20.58,0:07:27.90,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:07:27.90,0:07:30.08,Default,,0000,0000,0000,,So Sam, why don't you tell these folks
Dialogue: 0,0:07:30.08,0:07:33.45,Default,,0000,0000,0000,,what it's like being affected with this condition called progeria?
Dialogue: 0,0:07:33.45,0:07:37.26,Default,,0000,0000,0000,,Sam Burns: Well, progeria limits me in some ways.
Dialogue: 0,0:07:37.26,0:07:41.22,Default,,0000,0000,0000,,I cannot play sports or do physical activities,
Dialogue: 0,0:07:41.22,0:07:44.43,Default,,0000,0000,0000,,but I have been able to take interest in things
Dialogue: 0,0:07:44.43,0:07:47.40,Default,,0000,0000,0000,,that progeria, luckily, does not limit.
Dialogue: 0,0:07:47.40,0:07:49.96,Default,,0000,0000,0000,,But when there is something that I really do want to do
Dialogue: 0,0:07:49.96,0:07:52.98,Default,,0000,0000,0000,,that progeria gets in the way of, like marching band
Dialogue: 0,0:07:52.98,0:07:56.40,Default,,0000,0000,0000,,or umpiring, we always find a way to do it,
Dialogue: 0,0:07:56.40,0:07:59.92,Default,,0000,0000,0000,,and that just shows that progeria isn't in control of my life.
Dialogue: 0,0:07:59.92,0:08:01.63,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:08:01.63,0:08:03.67,Default,,0000,0000,0000,,Francis Collins: So what would you like to say to researchers
Dialogue: 0,0:08:03.67,0:08:06.76,Default,,0000,0000,0000,,here in the auditorium and others listening to this?
Dialogue: 0,0:08:06.76,0:08:09.36,Default,,0000,0000,0000,,What would you say to them both about research on progeria
Dialogue: 0,0:08:09.36,0:08:11.25,Default,,0000,0000,0000,,and maybe about other conditions as well?
Dialogue: 0,0:08:11.25,0:08:14.39,Default,,0000,0000,0000,,SB: Well, research on progeria has come so far
Dialogue: 0,0:08:14.39,0:08:16.64,Default,,0000,0000,0000,,in less than 15 years,
Dialogue: 0,0:08:16.64,0:08:21.00,Default,,0000,0000,0000,,and that just shows the drive that researchers can have
Dialogue: 0,0:08:21.00,0:08:24.42,Default,,0000,0000,0000,,to get this far, and it really means a lot
Dialogue: 0,0:08:24.42,0:08:27.67,Default,,0000,0000,0000,,to myself and other kids with progeria,
Dialogue: 0,0:08:27.67,0:08:30.50,Default,,0000,0000,0000,,and it shows that if that drive exists,
Dialogue: 0,0:08:30.50,0:08:33.10,Default,,0000,0000,0000,,anybody can cure any disease,
Dialogue: 0,0:08:33.10,0:08:37.05,Default,,0000,0000,0000,,and hopefully progeria can be cured in the near future,
Dialogue: 0,0:08:37.05,0:08:40.80,Default,,0000,0000,0000,,and so we can eliminate those 4,000 diseases
Dialogue: 0,0:08:40.80,0:08:43.81,Default,,0000,0000,0000,,that Francis was talking about.
Dialogue: 0,0:08:43.81,0:08:46.94,Default,,0000,0000,0000,,FC: Excellent. So Sam took the day off from school today
Dialogue: 0,0:08:46.94,0:08:52.07,Default,,0000,0000,0000,,to be here, and he is — (Applause) --
Dialogue: 0,0:08:52.07,0:08:56.89,Default,,0000,0000,0000,,He is, by the way, a straight-A+ student in the ninth grade
Dialogue: 0,0:08:56.89,0:08:58.22,Default,,0000,0000,0000,,in his school in Boston.
Dialogue: 0,0:08:58.22,0:09:00.42,Default,,0000,0000,0000,,Please join me in thanking and welcoming Sam.
Dialogue: 0,0:09:00.42,0:09:04.08,Default,,0000,0000,0000,,SB: Thank you very much. FC: Well done. Well done, buddy.
Dialogue: 0,0:09:04.08,0:09:15.90,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:09:16.89,0:09:18.60,Default,,0000,0000,0000,,So I just want to say a couple more things
Dialogue: 0,0:09:18.60,0:09:21.73,Default,,0000,0000,0000,,about that particular story, and then try to generalize
Dialogue: 0,0:09:21.73,0:09:24.23,Default,,0000,0000,0000,,how could we have stories of success
Dialogue: 0,0:09:24.23,0:09:27.74,Default,,0000,0000,0000,,all over the place for these diseases, as Sam says,
Dialogue: 0,0:09:27.74,0:09:30.26,Default,,0000,0000,0000,,these 4,000 that are waiting for answers.
Dialogue: 0,0:09:30.26,0:09:32.13,Default,,0000,0000,0000,,You might have noticed that the drug
Dialogue: 0,0:09:32.13,0:09:34.90,Default,,0000,0000,0000,,that is now in clinical trial for progeria
Dialogue: 0,0:09:34.90,0:09:36.67,Default,,0000,0000,0000,,is not a drug that was designed for that.
Dialogue: 0,0:09:36.67,0:09:39.53,Default,,0000,0000,0000,,It's such a rare disease, it would be hard for a company
Dialogue: 0,0:09:39.53,0:09:43.26,Default,,0000,0000,0000,,to justify spending hundreds of millions of dollars to generate a drug.
Dialogue: 0,0:09:43.26,0:09:45.42,Default,,0000,0000,0000,,This is a drug that was developed for cancer.
Dialogue: 0,0:09:45.42,0:09:47.58,Default,,0000,0000,0000,,Turned out, it didn't work very well for cancer,
Dialogue: 0,0:09:47.58,0:09:49.91,Default,,0000,0000,0000,,but it has exactly the right properties, the right shape,
Dialogue: 0,0:09:49.91,0:09:52.80,Default,,0000,0000,0000,,to work for progeria, and that's what's happened.
Dialogue: 0,0:09:52.80,0:09:56.03,Default,,0000,0000,0000,,Wouldn't it be great if we could do that more systematically?
Dialogue: 0,0:09:56.03,0:09:59.82,Default,,0000,0000,0000,,Could we, in fact, encourage all the companies that are out there
Dialogue: 0,0:09:59.82,0:10:01.66,Default,,0000,0000,0000,,that have drugs in their freezers
Dialogue: 0,0:10:01.66,0:10:03.86,Default,,0000,0000,0000,,that are known to be safe in humans
Dialogue: 0,0:10:03.86,0:10:06.16,Default,,0000,0000,0000,,but have never actually succeeded in terms
Dialogue: 0,0:10:06.16,0:10:09.01,Default,,0000,0000,0000,,of being effective for the treatments they were tried for?
Dialogue: 0,0:10:09.01,0:10:11.40,Default,,0000,0000,0000,,Now we're learning about all these new molecular pathways --
Dialogue: 0,0:10:11.40,0:10:14.47,Default,,0000,0000,0000,,some of those could be repositioned or repurposed,
Dialogue: 0,0:10:14.47,0:10:16.87,Default,,0000,0000,0000,,or whatever word you want to use, for new applications,
Dialogue: 0,0:10:16.87,0:10:19.84,Default,,0000,0000,0000,,basically teaching old drugs new tricks.
Dialogue: 0,0:10:19.84,0:10:22.53,Default,,0000,0000,0000,,That could be a phenomenal, valuable activity.
Dialogue: 0,0:10:22.53,0:10:25.58,Default,,0000,0000,0000,,We have many discussions now between NIH and companies
Dialogue: 0,0:10:25.58,0:10:27.70,Default,,0000,0000,0000,,about doing this that are looking very promising.
Dialogue: 0,0:10:27.70,0:10:30.31,Default,,0000,0000,0000,,And you could expect quite a lot to come from this.
Dialogue: 0,0:10:30.31,0:10:33.35,Default,,0000,0000,0000,,There are quite a number of success stories one can point to
Dialogue: 0,0:10:33.35,0:10:35.70,Default,,0000,0000,0000,,about how this has led to major advances.
Dialogue: 0,0:10:35.70,0:10:37.91,Default,,0000,0000,0000,,The first drug for HIV/AIDS
Dialogue: 0,0:10:37.91,0:10:39.64,Default,,0000,0000,0000,,was not developed for HIV/AIDS.
Dialogue: 0,0:10:39.64,0:10:42.16,Default,,0000,0000,0000,,It was developed for cancer. It was AZT.
Dialogue: 0,0:10:42.16,0:10:44.16,Default,,0000,0000,0000,,It didn't work very well for cancer, but became
Dialogue: 0,0:10:44.16,0:10:46.28,Default,,0000,0000,0000,,the first successful antiretroviral,
Dialogue: 0,0:10:46.28,0:10:48.85,Default,,0000,0000,0000,,and you can see from the table there are others as well.
Dialogue: 0,0:10:48.85,0:10:52.49,Default,,0000,0000,0000,,So how do we actually make that a more generalizable effort?
Dialogue: 0,0:10:52.49,0:10:54.72,Default,,0000,0000,0000,,Well, we have to come up with a partnership
Dialogue: 0,0:10:54.72,0:10:57.58,Default,,0000,0000,0000,,between academia, government, the private sector,
Dialogue: 0,0:10:57.58,0:11:00.03,Default,,0000,0000,0000,,and patient organizations to make that so.
Dialogue: 0,0:11:00.03,0:11:01.68,Default,,0000,0000,0000,,At NIH, we have started this new
Dialogue: 0,0:11:01.68,0:11:04.88,Default,,0000,0000,0000,,National Center for Advancing Translational Sciences.
Dialogue: 0,0:11:04.88,0:11:08.49,Default,,0000,0000,0000,,It just started last December, and this is one of its goals.
Dialogue: 0,0:11:08.49,0:11:09.94,Default,,0000,0000,0000,,Let me tell you another thing we could do.
Dialogue: 0,0:11:09.94,0:11:12.85,Default,,0000,0000,0000,,Wouldn't it be nice to be able to a test a drug
Dialogue: 0,0:11:12.85,0:11:15.22,Default,,0000,0000,0000,,to see if it's effective and safe
Dialogue: 0,0:11:15.22,0:11:17.33,Default,,0000,0000,0000,,without having to put patients at risk,
Dialogue: 0,0:11:17.33,0:11:19.88,Default,,0000,0000,0000,,because that first time you're never quite sure?
Dialogue: 0,0:11:19.88,0:11:22.03,Default,,0000,0000,0000,,How do we know, for instance, whether drugs are safe
Dialogue: 0,0:11:22.03,0:11:25.28,Default,,0000,0000,0000,,before we give them to people? We test them on animals.
Dialogue: 0,0:11:25.28,0:11:27.92,Default,,0000,0000,0000,,And it's not all that reliable, and it's costly,
Dialogue: 0,0:11:27.92,0:11:29.61,Default,,0000,0000,0000,,and it's time-consuming.
Dialogue: 0,0:11:29.61,0:11:32.47,Default,,0000,0000,0000,,Suppose we could do this instead on human cells.
Dialogue: 0,0:11:32.47,0:11:34.70,Default,,0000,0000,0000,,You probably know, if you've been paying attention
Dialogue: 0,0:11:34.70,0:11:36.00,Default,,0000,0000,0000,,to some of the science literature
Dialogue: 0,0:11:36.00,0:11:37.66,Default,,0000,0000,0000,,that you can now take a skin cell
Dialogue: 0,0:11:37.66,0:11:40.54,Default,,0000,0000,0000,,and encourage it to become a liver cell
Dialogue: 0,0:11:40.54,0:11:43.61,Default,,0000,0000,0000,,or a heart cell or a kidney cell or a brain cell for any of us.
Dialogue: 0,0:11:43.61,0:11:46.77,Default,,0000,0000,0000,,So what if you used those cells as your test
Dialogue: 0,0:11:46.77,0:11:49.71,Default,,0000,0000,0000,,for whether a drug is going to work and whether it's going to be safe?
Dialogue: 0,0:11:49.71,0:11:53.94,Default,,0000,0000,0000,,Here you see a picture of a lung on a chip.
Dialogue: 0,0:11:53.94,0:11:57.46,Default,,0000,0000,0000,,This is something created by the Wyss Institute in Boston,
Dialogue: 0,0:11:57.46,0:12:00.64,Default,,0000,0000,0000,,and what they have done here, if we can run the little video,
Dialogue: 0,0:12:00.64,0:12:02.77,Default,,0000,0000,0000,,is to take cells from an individual,
Dialogue: 0,0:12:02.77,0:12:05.88,Default,,0000,0000,0000,,turn them into the kinds of cells that are present in the lung,
Dialogue: 0,0:12:05.88,0:12:07.69,Default,,0000,0000,0000,,and determine what would happen
Dialogue: 0,0:12:07.69,0:12:10.76,Default,,0000,0000,0000,,if you added to this various drug compounds
Dialogue: 0,0:12:10.76,0:12:13.23,Default,,0000,0000,0000,,to see if they are toxic or safe.
Dialogue: 0,0:12:13.23,0:12:15.50,Default,,0000,0000,0000,,You can see this chip even breathes.
Dialogue: 0,0:12:15.50,0:12:18.12,Default,,0000,0000,0000,,It has an air channel. It has a blood channel.
Dialogue: 0,0:12:18.12,0:12:19.82,Default,,0000,0000,0000,,And it has cells in between
Dialogue: 0,0:12:19.82,0:12:22.26,Default,,0000,0000,0000,,that allow you to see what happens when you add a compound.
Dialogue: 0,0:12:22.26,0:12:24.03,Default,,0000,0000,0000,,Are those cells happy or not?
Dialogue: 0,0:12:24.03,0:12:27.06,Default,,0000,0000,0000,,You can do this same kind of chip technology
Dialogue: 0,0:12:27.06,0:12:29.27,Default,,0000,0000,0000,,for kidneys, for hearts, for muscles,
Dialogue: 0,0:12:29.27,0:12:31.74,Default,,0000,0000,0000,,all the places where you want to see whether a drug
Dialogue: 0,0:12:31.74,0:12:34.02,Default,,0000,0000,0000,,is going to be a problem, for the liver.
Dialogue: 0,0:12:34.02,0:12:37.06,Default,,0000,0000,0000,,And ultimately, because you can do this for the individual,
Dialogue: 0,0:12:37.06,0:12:39.28,Default,,0000,0000,0000,,we could even see this moving to the point
Dialogue: 0,0:12:39.28,0:12:42.72,Default,,0000,0000,0000,,where the ability to develop and test medicines
Dialogue: 0,0:12:42.72,0:12:45.90,Default,,0000,0000,0000,,will be you on a chip, what we're trying to say here is
Dialogue: 0,0:12:45.90,0:12:49.41,Default,,0000,0000,0000,,the individualizing of the process of developing drugs
Dialogue: 0,0:12:49.41,0:12:51.65,Default,,0000,0000,0000,,and testing their safety.
Dialogue: 0,0:12:51.65,0:12:53.31,Default,,0000,0000,0000,,So let me sum up.
Dialogue: 0,0:12:53.31,0:12:55.57,Default,,0000,0000,0000,,We are in a remarkable moment here.
Dialogue: 0,0:12:55.57,0:12:57.67,Default,,0000,0000,0000,,For me, at NIH now for almost 20 years,
Dialogue: 0,0:12:57.67,0:13:00.27,Default,,0000,0000,0000,,there has never been a time where there was more excitement
Dialogue: 0,0:13:00.27,0:13:02.86,Default,,0000,0000,0000,,about the potential that lies in front of us.
Dialogue: 0,0:13:02.86,0:13:04.65,Default,,0000,0000,0000,,We have made all these discoveries
Dialogue: 0,0:13:04.65,0:13:07.01,Default,,0000,0000,0000,,pouring out of laboratories across the world.
Dialogue: 0,0:13:07.01,0:13:10.37,Default,,0000,0000,0000,,What do we need to capitalize on this? First of all, we need resources.
Dialogue: 0,0:13:10.37,0:13:13.93,Default,,0000,0000,0000,,This is research that's high-risk, sometimes high-cost.
Dialogue: 0,0:13:13.93,0:13:15.90,Default,,0000,0000,0000,,The payoff is enormous, both in terms of health
Dialogue: 0,0:13:15.90,0:13:18.78,Default,,0000,0000,0000,,and in terms of economic growth. We need to support that.
Dialogue: 0,0:13:18.78,0:13:21.08,Default,,0000,0000,0000,,Second, we need new kinds of partnerships
Dialogue: 0,0:13:21.08,0:13:23.30,Default,,0000,0000,0000,,between academia and government and the private sector
Dialogue: 0,0:13:23.30,0:13:26.65,Default,,0000,0000,0000,,and patient organizations, just like the one I've been describing here,
Dialogue: 0,0:13:26.65,0:13:30.23,Default,,0000,0000,0000,,in terms of the way in which we could go after repurposing new compounds.
Dialogue: 0,0:13:30.23,0:13:33.46,Default,,0000,0000,0000,,And third, and maybe most important, we need talent.
Dialogue: 0,0:13:33.46,0:13:35.61,Default,,0000,0000,0000,,We need the best and the brightest
Dialogue: 0,0:13:35.61,0:13:38.46,Default,,0000,0000,0000,,from many different disciplines to come and join this effort --
Dialogue: 0,0:13:38.46,0:13:40.91,Default,,0000,0000,0000,,all ages, all different groups --
Dialogue: 0,0:13:40.91,0:13:42.100,Default,,0000,0000,0000,,because this is the time, folks.
Dialogue: 0,0:13:42.100,0:13:46.62,Default,,0000,0000,0000,,This is the 21st-century biology that you've been waiting for,
Dialogue: 0,0:13:46.62,0:13:49.08,Default,,0000,0000,0000,,and we have the chance to take that
Dialogue: 0,0:13:49.08,0:13:51.57,Default,,0000,0000,0000,,and turn it into something which will, in fact,
Dialogue: 0,0:13:51.57,0:13:53.90,Default,,0000,0000,0000,,knock out disease. That's my goal.
Dialogue: 0,0:13:53.90,0:13:55.79,Default,,0000,0000,0000,,I hope that's your goal.
Dialogue: 0,0:13:55.79,0:13:58.47,Default,,0000,0000,0000,,I think it'll be the goal of the poets and the muppets
Dialogue: 0,0:13:58.47,0:14:00.48,Default,,0000,0000,0000,,and the surfers and the bankers
Dialogue: 0,0:14:00.48,0:14:02.75,Default,,0000,0000,0000,,and all the other people who join this stage
Dialogue: 0,0:14:02.75,0:14:04.50,Default,,0000,0000,0000,,and think about what we're trying to do here
Dialogue: 0,0:14:04.50,0:14:05.67,Default,,0000,0000,0000,,and why it matters.
Dialogue: 0,0:14:05.67,0:14:08.44,Default,,0000,0000,0000,,It matters for now. It matters as soon as possible.
Dialogue: 0,0:14:08.44,0:14:11.56,Default,,0000,0000,0000,,If you don't believe me, just ask Sam.
Dialogue: 0,0:14:11.56,0:14:13.00,Default,,0000,0000,0000,,Thank you all very much.
Dialogue: 0,0:14:13.00,0:14:17.83,Default,,0000,0000,0000,,(Applause)