We need better drugs -- now
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0:01 - 0:03So let me ask for a show of hands.
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0:03 - 0:07How many people here are over the age of 48?
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0:07 - 0:10Well, there do seem to be a few.
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0:10 - 0:12Well, congratulations,
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0:12 - 0:16because if you look at this particular slide of U.S. life expectancy,
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0:16 - 0:19you are now in excess of the average life span
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0:19 - 0:22of somebody who was born in 1900.
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0:22 - 0:25But look what happened in the course of that century.
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0:25 - 0:27If you follow that curve,
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0:27 - 0:30you'll see that it starts way down there.
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0:30 - 0:32There's that dip there for the 1918 flu.
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0:32 - 0:35And here we are at 2010,
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0:35 - 0:38average life expectancy of a child born today, age 79,
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0:38 - 0:40and we are not done yet.
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0:40 - 0:41Now, that's the good news.
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0:41 - 0:43But there's still a lot of work to do.
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0:43 - 0:44So, for instance, if you ask,
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0:44 - 0:47how many diseases do we now know
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0:47 - 0:49the exact molecular basis?
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0:49 - 0:53Turns out it's about 4,000, which is pretty amazing,
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0:53 - 0:55because most of those molecular discoveries
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0:55 - 0:58have just happened in the last little while.
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0:58 - 1:01It's exciting to see that in terms of what we've learned,
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1:01 - 1:03but how many of those 4,000 diseases
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1:03 - 1:05now have treatments available?
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1:05 - 1:07Only about 250.
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1:07 - 1:10So we have this huge challenge, this huge gap.
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1:10 - 1:13You would think this wouldn't be too hard,
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1:13 - 1:14that we would simply have the ability
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1:14 - 1:17to take this fundamental information that we're learning
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1:17 - 1:20about how it is that basic biology teaches us
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1:20 - 1:22about the causes of disease
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1:22 - 1:25and build a bridge across this yawning gap
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1:25 - 1:28between what we've learned about basic science
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1:28 - 1:29and its application,
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1:29 - 1:32a bridge that would look maybe something like this,
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1:32 - 1:36where you'd have to put together a nice shiny way
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1:36 - 1:39to get from one side to the other.
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1:39 - 1:42Well, wouldn't it be nice if it was that easy?
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1:42 - 1:44Unfortunately, it's not.
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1:44 - 1:46In reality, trying to go from fundamental knowledge
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1:46 - 1:49to its application is more like this.
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1:49 - 1:51There are no shiny bridges.
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1:51 - 1:52You sort of place your bets.
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1:52 - 1:54Maybe you've got a swimmer and a rowboat
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1:54 - 1:56and a sailboat and a tugboat
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1:56 - 1:58and you set them off on their way,
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1:58 - 2:00and the rains come and the lightning flashes,
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2:00 - 2:02and oh my gosh, there are sharks in the water
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2:02 - 2:04and the swimmer gets into trouble,
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2:04 - 2:05and, uh oh, the swimmer drowned
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2:05 - 2:09and the sailboat capsized,
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2:09 - 2:10and that tugboat, well, it hit the rocks,
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2:10 - 2:13and maybe if you're lucky, somebody gets across.
-
2:13 - 2:15Well, what does this really look like?
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2:15 - 2:17Well, what is it to make a therapeutic, anyway?
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2:17 - 2:20What's a drug? A drug is made up
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2:20 - 2:22of a small molecule of hydrogen, carbon,
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2:22 - 2:25oxygen, nitrogen, and a few other atoms
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2:25 - 2:27all cobbled together in a shape,
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2:27 - 2:29and it's those shapes that determine whether, in fact,
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2:29 - 2:33that particular drug is going to hit its target.
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2:33 - 2:35Is it going to land where it's supposed to?
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2:35 - 2:38So look at this picture here -- a lot of shapes dancing around for you.
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2:38 - 2:40Now what you need to do, if you're trying to develop
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2:40 - 2:42a new treatment for autism
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2:42 - 2:44or Alzheimer's disease or cancer
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2:44 - 2:46is to find the right shape in that mix
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2:46 - 2:49that will ultimately provide benefit and will be safe.
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2:49 - 2:52And when you look at what happens to that pipeline,
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2:52 - 2:53you start out maybe with thousands,
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2:53 - 2:55tens of thousands of compounds.
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2:55 - 2:57You weed down through various steps
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2:57 - 2:59that cause many of these to fail.
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2:59 - 3:02Ultimately, maybe you can run a clinical trial with four or five of these,
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3:02 - 3:05and if all goes well, 14 years after you started,
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3:05 - 3:07you will get one approval.
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3:07 - 3:09And it will cost you upwards of a billion dollars
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3:09 - 3:11for that one success.
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3:11 - 3:14So we have to look at this pipeline the way an engineer would,
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3:14 - 3:16and say, "How can we do better?"
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3:16 - 3:18And that's the main theme of what I want to say to you this morning.
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3:18 - 3:20How can we make this go faster?
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3:20 - 3:23How can we make it more successful?
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3:23 - 3:25Well, let me tell you about a few examples
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3:25 - 3:27where this has actually worked.
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3:27 - 3:30One that has just happened in the last few months
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3:30 - 3:33is the successful approval of a drug for cystic fibrosis.
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3:33 - 3:35But it's taken a long time to get there.
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3:35 - 3:40Cystic fibrosis had its molecular cause discovered in 1989
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3:40 - 3:42by my group working with another group in Toronto,
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3:42 - 3:44discovering what the mutation was in a particular gene
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3:44 - 3:46on chromosome 7.
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3:46 - 3:48That picture you see there?
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3:48 - 3:50Here it is. That's the same kid.
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3:50 - 3:53That's Danny Bessette, 23 years later,
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3:53 - 3:55because this is the year,
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3:55 - 3:57and it's also the year where Danny got married,
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3:57 - 4:00where we have, for the first time, the approval by the FDA
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4:00 - 4:04of a drug that precisely targets the defect in cystic fibrosis
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4:04 - 4:06based upon all this molecular understanding.
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4:06 - 4:07That's the good news.
-
4:07 - 4:11The bad news is, this drug doesn't actually treat all cases of cystic fibrosis,
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4:11 - 4:13and it won't work for Danny, and we're still waiting
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4:13 - 4:15for that next generation to help him.
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4:15 - 4:19But it took 23 years to get this far. That's too long.
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4:19 - 4:20How do we go faster?
-
4:20 - 4:23Well, one way to go faster is to take advantage of technology,
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4:23 - 4:26and a very important technology that we depend on
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4:26 - 4:28for all of this is the human genome,
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4:28 - 4:30the ability to be able to look at a chromosome,
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4:30 - 4:33to unzip it, to pull out all the DNA,
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4:33 - 4:36and to be able to then read out the letters in that DNA code,
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4:36 - 4:38the A's, C's, G's and T's
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4:38 - 4:41that are our instruction book and the instruction book for all living things,
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4:41 - 4:43and the cost of doing this,
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4:43 - 4:46which used to be in the hundreds of millions of dollars,
-
4:46 - 4:48has in the course of the last 10 years
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4:48 - 4:50fallen faster than Moore's Law, down to the point
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4:50 - 4:54where it is less than 10,000 dollars today to have your genome sequenced, or mine,
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4:54 - 4:58and we're headed for the $1,000 genome fairly soon.
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4:58 - 4:59Well, that's exciting.
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4:59 - 5:03How does that play out in terms of application to a disease?
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5:03 - 5:05I want to tell you about another disorder.
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5:05 - 5:07This one is a disorder which is quite rare.
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5:07 - 5:10It's called Hutchinson-Gilford progeria,
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5:10 - 5:14and it is the most dramatic form of premature aging.
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5:14 - 5:17Only about one in every four million kids has this disease,
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5:17 - 5:21and in a simple way, what happens is,
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5:21 - 5:23because of a mutation in a particular gene,
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5:23 - 5:26a protein is made that's toxic to the cell
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5:26 - 5:28and it causes these individuals to age
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5:28 - 5:31at about seven times the normal rate.
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5:31 - 5:34Let me show you a video of what that does to the cell.
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5:34 - 5:37The normal cell, if you looked at it under the microscope,
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5:37 - 5:40would have a nucleus sitting in the middle of the cell,
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5:40 - 5:44which is nice and round and smooth in its boundaries
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5:44 - 5:46and it looks kind of like that.
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5:46 - 5:48A progeria cell, on the other hand,
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5:48 - 5:51because of this toxic protein called progerin,
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5:51 - 5:53has these lumps and bumps in it.
-
5:53 - 5:56So what we would like to do after discovering this
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5:56 - 5:58back in 2003
-
5:58 - 6:01is to come up with a way to try to correct that.
-
6:01 - 6:04Well again, by knowing something about the molecular pathways,
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6:04 - 6:06it was possible to pick
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6:06 - 6:09one of those many, many compounds that might have been useful
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6:09 - 6:10and try it out.
-
6:10 - 6:13In an experiment done in cell culture
-
6:13 - 6:15and shown here in a cartoon,
-
6:15 - 6:18if you take that particular compound
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6:18 - 6:21and you add it to that cell that has progeria,
-
6:21 - 6:23and you watch to see what happened,
-
6:23 - 6:26in just 72 hours, that cell becomes,
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6:26 - 6:28for all purposes that we can determine,
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6:28 - 6:30almost like a normal cell.
-
6:30 - 6:34Well that was exciting, but would it actually work in a real human being?
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6:34 - 6:38This has led, in the space of only four years
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6:38 - 6:41from the time the gene was discovered to the start of a clinical trial,
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6:41 - 6:44to a test of that very compound.
-
6:44 - 6:45And the kids that you see here
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6:45 - 6:48all volunteered to be part of this,
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6:48 - 6:4928 of them,
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6:49 - 6:53and you can see as soon as the picture comes up
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6:53 - 6:56that they are in fact a remarkable group of young people
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6:56 - 6:57all afflicted by this disease,
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6:57 - 7:00all looking quite similar to each other.
-
7:00 - 7:01And instead of telling you more about it,
-
7:01 - 7:05I'm going to invite one of them, Sam Berns from Boston,
-
7:05 - 7:08who's here this morning, to come up on the stage
-
7:08 - 7:10and tell us about his experience
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7:10 - 7:12as a child affected with progeria.
-
7:12 - 7:16Sam is 15 years old. His parents, Scott Berns and Leslie Gordon,
-
7:16 - 7:18both physicians, are here with us this morning as well.
-
7:18 - 7:21Sam, please have a seat.
-
7:21 - 7:28(Applause)
-
7:28 - 7:30So Sam, why don't you tell these folks
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7:30 - 7:33what it's like being affected with this condition called progeria?
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7:33 - 7:37Sam Burns: Well, progeria limits me in some ways.
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7:37 - 7:41I cannot play sports or do physical activities,
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7:41 - 7:44but I have been able to take interest in things
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7:44 - 7:47that progeria, luckily, does not limit.
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7:47 - 7:50But when there is something that I really do want to do
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7:50 - 7:53that progeria gets in the way of, like marching band
-
7:53 - 7:56or umpiring, we always find a way to do it,
-
7:56 - 8:00and that just shows that progeria isn't in control of my life.
-
8:00 - 8:02(Applause)
-
8:02 - 8:04Francis Collins: So what would you like to say to researchers
-
8:04 - 8:07here in the auditorium and others listening to this?
-
8:07 - 8:09What would you say to them both about research on progeria
-
8:09 - 8:11and maybe about other conditions as well?
-
8:11 - 8:14SB: Well, research on progeria has come so far
-
8:14 - 8:17in less than 15 years,
-
8:17 - 8:21and that just shows the drive that researchers can have
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8:21 - 8:24to get this far, and it really means a lot
-
8:24 - 8:28to myself and other kids with progeria,
-
8:28 - 8:30and it shows that if that drive exists,
-
8:30 - 8:33anybody can cure any disease,
-
8:33 - 8:37and hopefully progeria can be cured in the near future,
-
8:37 - 8:41and so we can eliminate those 4,000 diseases
-
8:41 - 8:44that Francis was talking about.
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8:44 - 8:47FC: Excellent. So Sam took the day off from school today
-
8:47 - 8:52to be here, and he is — (Applause) --
-
8:52 - 8:57He is, by the way, a straight-A+ student in the ninth grade
-
8:57 - 8:58in his school in Boston.
-
8:58 - 9:00Please join me in thanking and welcoming Sam.
-
9:00 - 9:04SB: Thank you very much. FC: Well done. Well done, buddy.
-
9:04 - 9:16(Applause)
-
9:17 - 9:19So I just want to say a couple more things
-
9:19 - 9:22about that particular story, and then try to generalize
-
9:22 - 9:24how could we have stories of success
-
9:24 - 9:28all over the place for these diseases, as Sam says,
-
9:28 - 9:30these 4,000 that are waiting for answers.
-
9:30 - 9:32You might have noticed that the drug
-
9:32 - 9:35that is now in clinical trial for progeria
-
9:35 - 9:37is not a drug that was designed for that.
-
9:37 - 9:40It's such a rare disease, it would be hard for a company
-
9:40 - 9:43to justify spending hundreds of millions of dollars to generate a drug.
-
9:43 - 9:45This is a drug that was developed for cancer.
-
9:45 - 9:48Turned out, it didn't work very well for cancer,
-
9:48 - 9:50but it has exactly the right properties, the right shape,
-
9:50 - 9:53to work for progeria, and that's what's happened.
-
9:53 - 9:56Wouldn't it be great if we could do that more systematically?
-
9:56 - 10:00Could we, in fact, encourage all the companies that are out there
-
10:00 - 10:02that have drugs in their freezers
-
10:02 - 10:04that are known to be safe in humans
-
10:04 - 10:06but have never actually succeeded in terms
-
10:06 - 10:09of being effective for the treatments they were tried for?
-
10:09 - 10:11Now we're learning about all these new molecular pathways --
-
10:11 - 10:14some of those could be repositioned or repurposed,
-
10:14 - 10:17or whatever word you want to use, for new applications,
-
10:17 - 10:20basically teaching old drugs new tricks.
-
10:20 - 10:23That could be a phenomenal, valuable activity.
-
10:23 - 10:26We have many discussions now between NIH and companies
-
10:26 - 10:28about doing this that are looking very promising.
-
10:28 - 10:30And you could expect quite a lot to come from this.
-
10:30 - 10:33There are quite a number of success stories one can point to
-
10:33 - 10:36about how this has led to major advances.
-
10:36 - 10:38The first drug for HIV/AIDS
-
10:38 - 10:40was not developed for HIV/AIDS.
-
10:40 - 10:42It was developed for cancer. It was AZT.
-
10:42 - 10:44It didn't work very well for cancer, but became
-
10:44 - 10:46the first successful antiretroviral,
-
10:46 - 10:49and you can see from the table there are others as well.
-
10:49 - 10:52So how do we actually make that a more generalizable effort?
-
10:52 - 10:55Well, we have to come up with a partnership
-
10:55 - 10:58between academia, government, the private sector,
-
10:58 - 11:00and patient organizations to make that so.
-
11:00 - 11:02At NIH, we have started this new
-
11:02 - 11:05National Center for Advancing Translational Sciences.
-
11:05 - 11:08It just started last December, and this is one of its goals.
-
11:08 - 11:10Let me tell you another thing we could do.
-
11:10 - 11:13Wouldn't it be nice to be able to a test a drug
-
11:13 - 11:15to see if it's effective and safe
-
11:15 - 11:17without having to put patients at risk,
-
11:17 - 11:20because that first time you're never quite sure?
-
11:20 - 11:22How do we know, for instance, whether drugs are safe
-
11:22 - 11:25before we give them to people? We test them on animals.
-
11:25 - 11:28And it's not all that reliable, and it's costly,
-
11:28 - 11:30and it's time-consuming.
-
11:30 - 11:32Suppose we could do this instead on human cells.
-
11:32 - 11:35You probably know, if you've been paying attention
-
11:35 - 11:36to some of the science literature
-
11:36 - 11:38that you can now take a skin cell
-
11:38 - 11:41and encourage it to become a liver cell
-
11:41 - 11:44or a heart cell or a kidney cell or a brain cell for any of us.
-
11:44 - 11:47So what if you used those cells as your test
-
11:47 - 11:50for whether a drug is going to work and whether it's going to be safe?
-
11:50 - 11:54Here you see a picture of a lung on a chip.
-
11:54 - 11:57This is something created by the Wyss Institute in Boston,
-
11:57 - 12:01and what they have done here, if we can run the little video,
-
12:01 - 12:03is to take cells from an individual,
-
12:03 - 12:06turn them into the kinds of cells that are present in the lung,
-
12:06 - 12:08and determine what would happen
-
12:08 - 12:11if you added to this various drug compounds
-
12:11 - 12:13to see if they are toxic or safe.
-
12:13 - 12:16You can see this chip even breathes.
-
12:16 - 12:18It has an air channel. It has a blood channel.
-
12:18 - 12:20And it has cells in between
-
12:20 - 12:22that allow you to see what happens when you add a compound.
-
12:22 - 12:24Are those cells happy or not?
-
12:24 - 12:27You can do this same kind of chip technology
-
12:27 - 12:29for kidneys, for hearts, for muscles,
-
12:29 - 12:32all the places where you want to see whether a drug
-
12:32 - 12:34is going to be a problem, for the liver.
-
12:34 - 12:37And ultimately, because you can do this for the individual,
-
12:37 - 12:39we could even see this moving to the point
-
12:39 - 12:43where the ability to develop and test medicines
-
12:43 - 12:46will be you on a chip, what we're trying to say here is
-
12:46 - 12:49the individualizing of the process of developing drugs
-
12:49 - 12:52and testing their safety.
-
12:52 - 12:53So let me sum up.
-
12:53 - 12:56We are in a remarkable moment here.
-
12:56 - 12:58For me, at NIH now for almost 20 years,
-
12:58 - 13:00there has never been a time where there was more excitement
-
13:00 - 13:03about the potential that lies in front of us.
-
13:03 - 13:05We have made all these discoveries
-
13:05 - 13:07pouring out of laboratories across the world.
-
13:07 - 13:10What do we need to capitalize on this? First of all, we need resources.
-
13:10 - 13:14This is research that's high-risk, sometimes high-cost.
-
13:14 - 13:16The payoff is enormous, both in terms of health
-
13:16 - 13:19and in terms of economic growth. We need to support that.
-
13:19 - 13:21Second, we need new kinds of partnerships
-
13:21 - 13:23between academia and government and the private sector
-
13:23 - 13:27and patient organizations, just like the one I've been describing here,
-
13:27 - 13:30in terms of the way in which we could go after repurposing new compounds.
-
13:30 - 13:33And third, and maybe most important, we need talent.
-
13:33 - 13:36We need the best and the brightest
-
13:36 - 13:38from many different disciplines to come and join this effort --
-
13:38 - 13:41all ages, all different groups --
-
13:41 - 13:43because this is the time, folks.
-
13:43 - 13:47This is the 21st-century biology that you've been waiting for,
-
13:47 - 13:49and we have the chance to take that
-
13:49 - 13:52and turn it into something which will, in fact,
-
13:52 - 13:54knock out disease. That's my goal.
-
13:54 - 13:56I hope that's your goal.
-
13:56 - 13:58I think it'll be the goal of the poets and the muppets
-
13:58 - 14:00and the surfers and the bankers
-
14:00 - 14:03and all the other people who join this stage
-
14:03 - 14:05and think about what we're trying to do here
-
14:05 - 14:06and why it matters.
-
14:06 - 14:08It matters for now. It matters as soon as possible.
-
14:08 - 14:12If you don't believe me, just ask Sam.
-
14:12 - 14:13Thank you all very much.
-
14:13 - 14:18(Applause)
- Title:
- We need better drugs -- now
- Speaker:
- Francis Collins
- Description:
-
Today we know the molecular cause of 4,000 diseases, but treatments are available for only 250 of them. So what’s taking so long? Geneticist and physician Francis Collins explains why systematic drug discovery is imperative, even for rare and complex diseases, and offers a few solutions -- like teaching old drugs new tricks.
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDTalks
- Duration:
- 14:40
Thu-Huong Ha edited English subtitles for We need better drugs -- now | ||
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Joseph Geni edited English subtitles for We need better drugs -- now | ||
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