[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.43,0:00:03.15,Default,,0000,0000,0000,,Now, I don't usually like cartoons,
Dialogue: 0,0:00:03.15,0:00:05.66,Default,,0000,0000,0000,,I don't think many of them are funny,
Dialogue: 0,0:00:05.66,0:00:10.89,Default,,0000,0000,0000,,I find them weird. But I love this cartoon from the New Yorker.
Dialogue: 0,0:00:10.89,0:00:13.50,Default,,0000,0000,0000,,(Text: Never, ever think outside the box.) (Laughter)
Dialogue: 0,0:00:13.50,0:00:15.97,Default,,0000,0000,0000,,So, the guy is telling the cat,
Dialogue: 0,0:00:15.97,0:00:21.34,Default,,0000,0000,0000,,don't you dare think outside the box.
Dialogue: 0,0:00:21.34,0:00:24.65,Default,,0000,0000,0000,,Well, I'm afraid I used to be the cat.
Dialogue: 0,0:00:24.65,0:00:27.70,Default,,0000,0000,0000,,I always wanted to be outside the box.
Dialogue: 0,0:00:27.70,0:00:31.19,Default,,0000,0000,0000,,And it's partly because I came to this field
Dialogue: 0,0:00:31.19,0:00:36.40,Default,,0000,0000,0000,,from a different background, chemist and a bacterial geneticist.
Dialogue: 0,0:00:36.40,0:00:39.00,Default,,0000,0000,0000,,So, what people were saying to me
Dialogue: 0,0:00:39.00,0:00:42.19,Default,,0000,0000,0000,,about the cause of cancer, sources of cancer,
Dialogue: 0,0:00:42.19,0:00:45.27,Default,,0000,0000,0000,,or, for that matter, why you are who you are,
Dialogue: 0,0:00:45.27,0:00:47.15,Default,,0000,0000,0000,,didn't make sense.
Dialogue: 0,0:00:47.15,0:00:50.19,Default,,0000,0000,0000,,So, let me quickly try and tell you why I thought that
Dialogue: 0,0:00:50.19,0:00:52.80,Default,,0000,0000,0000,,and how I went about it.
Dialogue: 0,0:00:52.80,0:00:55.23,Default,,0000,0000,0000,,So, to begin with, however,
Dialogue: 0,0:00:55.23,0:00:59.65,Default,,0000,0000,0000,,I have to give you a very, very quick lesson
Dialogue: 0,0:00:59.65,0:01:01.42,Default,,0000,0000,0000,,in developmental biology,
Dialogue: 0,0:01:01.42,0:01:05.48,Default,,0000,0000,0000,,with apologies to those of you who know some biology.
Dialogue: 0,0:01:05.48,0:01:08.50,Default,,0000,0000,0000,,So, when your mom and dad met,
Dialogue: 0,0:01:08.50,0:01:11.17,Default,,0000,0000,0000,,there is a fertilized egg,
Dialogue: 0,0:01:11.17,0:01:13.29,Default,,0000,0000,0000,,that round thing with that little blip.
Dialogue: 0,0:01:13.29,0:01:16.35,Default,,0000,0000,0000,,It grows and then it grows,
Dialogue: 0,0:01:16.35,0:01:20.50,Default,,0000,0000,0000,,and then it makes this handsome man.
Dialogue: 0,0:01:20.50,0:01:21.91,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:01:21.91,0:01:27.57,Default,,0000,0000,0000,,So, this guy, with all the cells in his body,
Dialogue: 0,0:01:27.57,0:01:31.78,Default,,0000,0000,0000,,all have the same genetic information.
Dialogue: 0,0:01:31.78,0:01:36.16,Default,,0000,0000,0000,,So how did his nose become his nose, his elbow his elbow,
Dialogue: 0,0:01:36.16,0:01:38.34,Default,,0000,0000,0000,,and why doesn't he get up one morning
Dialogue: 0,0:01:38.34,0:01:40.90,Default,,0000,0000,0000,,and have his nose turn into his foot?
Dialogue: 0,0:01:40.90,0:01:44.14,Default,,0000,0000,0000,,It could. It has the genetic information.
Dialogue: 0,0:01:44.14,0:01:45.34,Default,,0000,0000,0000,,You all remember, dolly,
Dialogue: 0,0:01:45.34,0:01:48.02,Default,,0000,0000,0000,,it came from a single mammary cell.
Dialogue: 0,0:01:48.02,0:01:49.96,Default,,0000,0000,0000,,So, why doesn't it do it?
Dialogue: 0,0:01:49.96,0:01:55.46,Default,,0000,0000,0000,,So, have a guess of how many cells he has in his body.
Dialogue: 0,0:01:55.46,0:02:02.86,Default,,0000,0000,0000,,Somewhere between 10 trillion to 70 trillion cells in his body.
Dialogue: 0,0:02:02.86,0:02:04.50,Default,,0000,0000,0000,,Trillion!
Dialogue: 0,0:02:04.50,0:02:09.14,Default,,0000,0000,0000,,Now, how did these cells, all with the same genetic material,
Dialogue: 0,0:02:09.14,0:02:11.35,Default,,0000,0000,0000,,make all those tissues?
Dialogue: 0,0:02:11.35,0:02:14.49,Default,,0000,0000,0000,,And so, the question I raised before
Dialogue: 0,0:02:14.49,0:02:18.11,Default,,0000,0000,0000,,becomes even more interesting if you thought about
Dialogue: 0,0:02:18.11,0:02:22.69,Default,,0000,0000,0000,,the enormity of this in every one of your bodies.
Dialogue: 0,0:02:22.69,0:02:25.69,Default,,0000,0000,0000,,Now, the dominant cancer theory would say
Dialogue: 0,0:02:25.69,0:02:28.00,Default,,0000,0000,0000,,that there is a single oncogene
Dialogue: 0,0:02:28.00,0:02:31.71,Default,,0000,0000,0000,,in a single cancer cell, and it would make you
Dialogue: 0,0:02:31.71,0:02:34.36,Default,,0000,0000,0000,,a cancer victim.
Dialogue: 0,0:02:34.36,0:02:38.02,Default,,0000,0000,0000,,Well, this did not make sense to me.
Dialogue: 0,0:02:38.02,0:02:41.21,Default,,0000,0000,0000,,Do you even know how a trillion looks?
Dialogue: 0,0:02:41.21,0:02:42.92,Default,,0000,0000,0000,,Now, let's look at it.
Dialogue: 0,0:02:42.92,0:02:47.97,Default,,0000,0000,0000,,There it comes, these zeroes after zeroes after zeroes.
Dialogue: 0,0:02:47.97,0:02:54.78,Default,,0000,0000,0000,,Now, if .0001 of these cells got mutated,
Dialogue: 0,0:02:54.78,0:03:00.04,Default,,0000,0000,0000,,and .00001 got cancer, you will be a lump of cancer.
Dialogue: 0,0:03:00.04,0:03:02.34,Default,,0000,0000,0000,,You will have cancer all over you. And you're not.
Dialogue: 0,0:03:02.34,0:03:04.65,Default,,0000,0000,0000,,Why not?
Dialogue: 0,0:03:04.65,0:03:08.37,Default,,0000,0000,0000,,So, I decided over the years,
Dialogue: 0,0:03:08.37,0:03:10.30,Default,,0000,0000,0000,,because of a series of experiments
Dialogue: 0,0:03:10.30,0:03:15.18,Default,,0000,0000,0000,,that this is because of context and architecture.
Dialogue: 0,0:03:15.18,0:03:17.35,Default,,0000,0000,0000,,And let me quickly tell you
Dialogue: 0,0:03:17.35,0:03:21.28,Default,,0000,0000,0000,,some crucial experiment that was able to actually show this.
Dialogue: 0,0:03:21.28,0:03:25.19,Default,,0000,0000,0000,,To begin with, I came to work with this virus
Dialogue: 0,0:03:25.19,0:03:28.58,Default,,0000,0000,0000,,that causes that ugly tumor in the chicken.
Dialogue: 0,0:03:28.58,0:03:31.94,Default,,0000,0000,0000,,Rous discovered this in 1911.
Dialogue: 0,0:03:31.94,0:03:35.51,Default,,0000,0000,0000,,It was the first cancer virus discovered,
Dialogue: 0,0:03:35.51,0:03:40.40,Default,,0000,0000,0000,,and when I call it "oncogene," meaning "cancer gene."
Dialogue: 0,0:03:40.40,0:03:43.31,Default,,0000,0000,0000,,So, he made a filtrate, he took this filter
Dialogue: 0,0:03:43.31,0:03:47.57,Default,,0000,0000,0000,,which was the liquid after he passed the tumor through a filter,
Dialogue: 0,0:03:47.57,0:03:51.57,Default,,0000,0000,0000,,and he injected it to another chicken, and he got another tumor.
Dialogue: 0,0:03:51.57,0:03:54.28,Default,,0000,0000,0000,,So, scientists were very excited,
Dialogue: 0,0:03:54.28,0:03:56.45,Default,,0000,0000,0000,,and they said, a single oncogene can do it.
Dialogue: 0,0:03:56.45,0:03:58.74,Default,,0000,0000,0000,,All you need is a single oncogene.
Dialogue: 0,0:03:58.74,0:04:01.64,Default,,0000,0000,0000,,So, they put the cells in cultures, chicken cells,
Dialogue: 0,0:04:01.64,0:04:03.67,Default,,0000,0000,0000,,dumped the virus on it,
Dialogue: 0,0:04:03.67,0:04:05.12,Default,,0000,0000,0000,,and it would pile up,
Dialogue: 0,0:04:05.12,0:04:08.14,Default,,0000,0000,0000,,and they would say, this is malignant and this is normal.
Dialogue: 0,0:04:08.14,0:04:10.16,Default,,0000,0000,0000,,And again this didn't make sense to me.
Dialogue: 0,0:04:10.16,0:04:13.45,Default,,0000,0000,0000,,So for various reasons, we took this oncogene,
Dialogue: 0,0:04:13.45,0:04:15.76,Default,,0000,0000,0000,,attached it to a blue marker,
Dialogue: 0,0:04:15.76,0:04:18.77,Default,,0000,0000,0000,,and we injected it into the embryos.
Dialogue: 0,0:04:18.77,0:04:22.96,Default,,0000,0000,0000,,Now look at that. There is that beautiful feather in the embryo.
Dialogue: 0,0:04:22.96,0:04:27.24,Default,,0000,0000,0000,,Every one of those blue cells are a cancer gene
Dialogue: 0,0:04:27.24,0:04:31.66,Default,,0000,0000,0000,,inside a cancer cell, and they're part of the feather.
Dialogue: 0,0:04:31.66,0:04:36.26,Default,,0000,0000,0000,,So, when we dissociated the feather and put it in a dish,
Dialogue: 0,0:04:36.26,0:04:38.97,Default,,0000,0000,0000,,we got a mass of blue cells.
Dialogue: 0,0:04:38.97,0:04:40.43,Default,,0000,0000,0000,,So, in the chicken you get a tumor,
Dialogue: 0,0:04:40.43,0:04:42.14,Default,,0000,0000,0000,,in the embryo you don't,
Dialogue: 0,0:04:42.14,0:04:46.13,Default,,0000,0000,0000,,you dissociate, you put it in a dish, you get another tumor.
Dialogue: 0,0:04:46.13,0:04:47.35,Default,,0000,0000,0000,,What does that mean?
Dialogue: 0,0:04:47.35,0:04:50.34,Default,,0000,0000,0000,,That means that microenvironment
Dialogue: 0,0:04:50.34,0:04:54.35,Default,,0000,0000,0000,,and the context which surrounds those cells
Dialogue: 0,0:04:54.35,0:05:01.27,Default,,0000,0000,0000,,actually are telling the cancer gene and the cancer cell what to do.
Dialogue: 0,0:05:01.27,0:05:04.58,Default,,0000,0000,0000,,Now, let's take a normal example.
Dialogue: 0,0:05:04.58,0:05:07.77,Default,,0000,0000,0000,,The normal example, let's take the human mammary gland.
Dialogue: 0,0:05:07.77,0:05:09.25,Default,,0000,0000,0000,,I work on breast cancer.
Dialogue: 0,0:05:09.25,0:05:12.26,Default,,0000,0000,0000,,So, here is a lovely human breast.
Dialogue: 0,0:05:12.26,0:05:14.20,Default,,0000,0000,0000,,And many of you know how it looks,
Dialogue: 0,0:05:14.20,0:05:17.06,Default,,0000,0000,0000,,except that inside that breast, there are all these
Dialogue: 0,0:05:17.06,0:05:20.44,Default,,0000,0000,0000,,pretty, developing, tree-like structures.
Dialogue: 0,0:05:20.44,0:05:23.33,Default,,0000,0000,0000,,So, we decided that what we like to do
Dialogue: 0,0:05:23.33,0:05:26.29,Default,,0000,0000,0000,,is take just a bit of that mammary gland,
Dialogue: 0,0:05:26.29,0:05:28.32,Default,,0000,0000,0000,,which is called an "acinus,"
Dialogue: 0,0:05:28.32,0:05:31.97,Default,,0000,0000,0000,,where there are all these little things inside the breast
Dialogue: 0,0:05:31.97,0:05:35.51,Default,,0000,0000,0000,,where the milk goes, and the end of the nipple
Dialogue: 0,0:05:35.51,0:05:39.05,Default,,0000,0000,0000,,comes through that little tube when the baby sucks.
Dialogue: 0,0:05:39.05,0:05:42.46,Default,,0000,0000,0000,,And we said, wonderful! Look at this pretty structure.
Dialogue: 0,0:05:42.46,0:05:46.23,Default,,0000,0000,0000,,We want to make this a structure, and ask the question,
Dialogue: 0,0:05:46.23,0:05:47.93,Default,,0000,0000,0000,,how do the cells do that?
Dialogue: 0,0:05:47.93,0:05:49.72,Default,,0000,0000,0000,,So, we took the red cells --
Dialogue: 0,0:05:49.72,0:05:52.97,Default,,0000,0000,0000,,you see the red cells are surrounded by blue,
Dialogue: 0,0:05:52.97,0:05:56.30,Default,,0000,0000,0000,,other cells that squeeze them, and behind it
Dialogue: 0,0:05:56.30,0:06:00.02,Default,,0000,0000,0000,,is material that people thought was mainly inert,
Dialogue: 0,0:06:00.02,0:06:03.62,Default,,0000,0000,0000,,and it was just having a structure to keep the shape,
Dialogue: 0,0:06:03.62,0:06:06.54,Default,,0000,0000,0000,,and so we first photographed it
Dialogue: 0,0:06:06.54,0:06:09.31,Default,,0000,0000,0000,,with the electron microscope years and years ago,
Dialogue: 0,0:06:09.31,0:06:12.37,Default,,0000,0000,0000,,and you see this cell is actually quite pretty.
Dialogue: 0,0:06:12.37,0:06:14.83,Default,,0000,0000,0000,,It has a bottom, it has a top,
Dialogue: 0,0:06:14.83,0:06:17.51,Default,,0000,0000,0000,,it is secreting gobs and gobs of milk,
Dialogue: 0,0:06:17.51,0:06:20.70,Default,,0000,0000,0000,,because it just came from an early pregnant mouse.
Dialogue: 0,0:06:20.70,0:06:23.03,Default,,0000,0000,0000,,You take these cells, you put them in a dish,
Dialogue: 0,0:06:23.03,0:06:26.38,Default,,0000,0000,0000,,and within three days, they look like that.
Dialogue: 0,0:06:26.38,0:06:29.54,Default,,0000,0000,0000,,They completely forget.
Dialogue: 0,0:06:29.54,0:06:32.34,Default,,0000,0000,0000,,So you take them out, you put them in a dish,
Dialogue: 0,0:06:32.34,0:06:35.00,Default,,0000,0000,0000,,they don't make milk. They completely forget.
Dialogue: 0,0:06:35.00,0:06:39.90,Default,,0000,0000,0000,,For example, here is a lovely yellow droplet of milk
Dialogue: 0,0:06:39.90,0:06:42.15,Default,,0000,0000,0000,,on the left, there is nothing on the right.
Dialogue: 0,0:06:42.15,0:06:45.88,Default,,0000,0000,0000,,Look at the nuclei. The nuclei in the cell on the left
Dialogue: 0,0:06:45.88,0:06:49.38,Default,,0000,0000,0000,,is in the animal, the one on the right is in a dish.
Dialogue: 0,0:06:49.38,0:06:52.12,Default,,0000,0000,0000,,They are completely different from each other.
Dialogue: 0,0:06:52.12,0:06:54.14,Default,,0000,0000,0000,,So, what does this tell you?
Dialogue: 0,0:06:54.14,0:06:59.11,Default,,0000,0000,0000,,This tells you that here also, context overrides.
Dialogue: 0,0:06:59.11,0:07:02.49,Default,,0000,0000,0000,,In different contexts, cells do different things.
Dialogue: 0,0:07:02.49,0:07:05.24,Default,,0000,0000,0000,,But how does context signal?
Dialogue: 0,0:07:05.24,0:07:07.78,Default,,0000,0000,0000,,So, Einstein said that
Dialogue: 0,0:07:07.78,0:07:14.43,Default,,0000,0000,0000,,"For an idea that does not first seem insane, there is no hope."
Dialogue: 0,0:07:14.43,0:07:20.39,Default,,0000,0000,0000,,So, you can imagine the amount of skepticism
Dialogue: 0,0:07:20.39,0:07:22.79,Default,,0000,0000,0000,,I received -- couldn't get money,
Dialogue: 0,0:07:22.79,0:07:24.74,Default,,0000,0000,0000,,couldn't do a whole lot of other things,
Dialogue: 0,0:07:24.74,0:07:26.46,Default,,0000,0000,0000,,but I'm so glad it all worked out.
Dialogue: 0,0:07:26.46,0:07:30.28,Default,,0000,0000,0000,,So, we made a section of the mammary gland of the mouse,
Dialogue: 0,0:07:30.28,0:07:33.46,Default,,0000,0000,0000,,and all those lovely acini are there,
Dialogue: 0,0:07:33.46,0:07:37.67,Default,,0000,0000,0000,,every one of those with the red around them are an acinus,
Dialogue: 0,0:07:37.67,0:07:41.37,Default,,0000,0000,0000,,and we said okay, we are going to try and make this,
Dialogue: 0,0:07:41.37,0:07:44.60,Default,,0000,0000,0000,,and I said, maybe that red stuff
Dialogue: 0,0:07:44.60,0:07:49.72,Default,,0000,0000,0000,,around the acinus that people think there's just a structural scaffold,
Dialogue: 0,0:07:49.72,0:07:51.66,Default,,0000,0000,0000,,maybe it has information,
Dialogue: 0,0:07:51.66,0:07:56.23,Default,,0000,0000,0000,,maybe it tells the cells what to do, maybe it tells the nucleus what to do.
Dialogue: 0,0:07:56.23,0:08:00.51,Default,,0000,0000,0000,,So I said, extracellular matrix, which is this stuff
Dialogue: 0,0:08:00.51,0:08:04.90,Default,,0000,0000,0000,,called ECM, signals and actually tells the cells what to do.
Dialogue: 0,0:08:04.90,0:08:08.67,Default,,0000,0000,0000,,So, we decided to make things that would look like that.
Dialogue: 0,0:08:08.67,0:08:11.55,Default,,0000,0000,0000,,We found some gooey material
Dialogue: 0,0:08:11.55,0:08:14.43,Default,,0000,0000,0000,,that had the right extracellular matrix in it,
Dialogue: 0,0:08:14.43,0:08:16.97,Default,,0000,0000,0000,,we put the cells in it, and lo and behold,
Dialogue: 0,0:08:16.97,0:08:19.79,Default,,0000,0000,0000,,in about four days, they got reorganized
Dialogue: 0,0:08:19.79,0:08:23.20,Default,,0000,0000,0000,,and on the right, is what we can make in culture.
Dialogue: 0,0:08:23.20,0:08:27.69,Default,,0000,0000,0000,,On the left is what's inside the animal, we call it in vivo,
Dialogue: 0,0:08:27.69,0:08:30.28,Default,,0000,0000,0000,,and the one in culture was full of milk,
Dialogue: 0,0:08:30.28,0:08:33.08,Default,,0000,0000,0000,,the lovely red there is full of milk.
Dialogue: 0,0:08:33.08,0:08:36.49,Default,,0000,0000,0000,,So, we Got Milk, for the American audience.
Dialogue: 0,0:08:36.49,0:08:41.84,Default,,0000,0000,0000,,All right. And here is this beautiful human cell,
Dialogue: 0,0:08:41.84,0:08:46.78,Default,,0000,0000,0000,,and you can imagine that here also, context goes.
Dialogue: 0,0:08:46.78,0:08:49.50,Default,,0000,0000,0000,,So, what do we do now?
Dialogue: 0,0:08:49.50,0:08:51.72,Default,,0000,0000,0000,,I made a radical hypothesis.
Dialogue: 0,0:08:51.72,0:08:58.38,Default,,0000,0000,0000,,I said, if it's true that architecture is dominant,
Dialogue: 0,0:08:58.38,0:09:02.87,Default,,0000,0000,0000,,architecture restored to a cancer cell
Dialogue: 0,0:09:02.87,0:09:05.86,Default,,0000,0000,0000,,should make the cancer cell think it's normal.
Dialogue: 0,0:09:05.86,0:09:07.34,Default,,0000,0000,0000,,Could this be done?
Dialogue: 0,0:09:07.34,0:09:09.87,Default,,0000,0000,0000,,So, we tried it.
Dialogue: 0,0:09:09.87,0:09:11.91,Default,,0000,0000,0000,,In order to do that, however,
Dialogue: 0,0:09:11.91,0:09:16.79,Default,,0000,0000,0000,,we needed to have a method of distinguishing normal from malignant,
Dialogue: 0,0:09:16.79,0:09:20.79,Default,,0000,0000,0000,,and on the left is the single normal cell,
Dialogue: 0,0:09:20.79,0:09:24.75,Default,,0000,0000,0000,,human breast, put in three-dimensional gooey gel
Dialogue: 0,0:09:24.75,0:09:28.62,Default,,0000,0000,0000,,that has extracellular matrix, it makes all these beautiful structures.
Dialogue: 0,0:09:28.62,0:09:31.51,Default,,0000,0000,0000,,On the right, you see it looks very ugly,
Dialogue: 0,0:09:31.51,0:09:33.15,Default,,0000,0000,0000,,the cells continue to grow,
Dialogue: 0,0:09:33.15,0:09:34.73,Default,,0000,0000,0000,,the normal ones stop.
Dialogue: 0,0:09:34.73,0:09:37.56,Default,,0000,0000,0000,,And you see here in higher magnification
Dialogue: 0,0:09:37.56,0:09:41.91,Default,,0000,0000,0000,,the normal acinus and the ugly tumor.
Dialogue: 0,0:09:41.91,0:09:46.14,Default,,0000,0000,0000,,So we said, what is on the surface of these ugly tumors?
Dialogue: 0,0:09:46.14,0:09:48.31,Default,,0000,0000,0000,,Could we calm them down --
Dialogue: 0,0:09:48.31,0:09:53.23,Default,,0000,0000,0000,,they were signaling like crazy and they have pathways all messed up --
Dialogue: 0,0:09:53.23,0:09:56.29,Default,,0000,0000,0000,,and make them to the level of the normal?
Dialogue: 0,0:09:56.29,0:10:01.01,Default,,0000,0000,0000,,Well, it was wonderful. Boggles my mind.
Dialogue: 0,0:10:01.01,0:10:03.17,Default,,0000,0000,0000,,This is what we got.
Dialogue: 0,0:10:03.17,0:10:06.85,Default,,0000,0000,0000,,We can revert the malignant phenotype.
Dialogue: 0,0:10:06.85,0:10:09.42,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:10:09.42,0:10:12.53,Default,,0000,0000,0000,,And in order to show you that the malignant phenotype
Dialogue: 0,0:10:12.53,0:10:14.25,Default,,0000,0000,0000,,I didn't just choose one,
Dialogue: 0,0:10:14.25,0:10:17.02,Default,,0000,0000,0000,,here are little movies, sort of fuzzy,
Dialogue: 0,0:10:17.02,0:10:20.67,Default,,0000,0000,0000,,but you see that on the left are the malignant cells,
Dialogue: 0,0:10:20.67,0:10:22.02,Default,,0000,0000,0000,,all of them are malignant,
Dialogue: 0,0:10:22.02,0:10:26.82,Default,,0000,0000,0000,,we add one single inhibitor in the beginning,
Dialogue: 0,0:10:26.82,0:10:30.28,Default,,0000,0000,0000,,and look what happens, they all look like that.
Dialogue: 0,0:10:30.28,0:10:33.72,Default,,0000,0000,0000,,We inject them into the mouse, the ones on the right,
Dialogue: 0,0:10:33.72,0:10:35.96,Default,,0000,0000,0000,,and none of them would make tumors.
Dialogue: 0,0:10:35.96,0:10:39.50,Default,,0000,0000,0000,,We inject the other ones in the mouse, 100 percent tumors.
Dialogue: 0,0:10:39.50,0:10:42.17,Default,,0000,0000,0000,,So, it's a new way of thinking about cancer,
Dialogue: 0,0:10:42.17,0:10:44.57,Default,,0000,0000,0000,,it's a hopeful way of thinking about cancer.
Dialogue: 0,0:10:44.57,0:10:48.55,Default,,0000,0000,0000,,We should be able to be dealing with these things at this level,
Dialogue: 0,0:10:48.55,0:10:54.46,Default,,0000,0000,0000,,and these conclusions say that growth and malignant behavior
Dialogue: 0,0:10:54.46,0:10:58.33,Default,,0000,0000,0000,,is regulated at the level of tissue organization
Dialogue: 0,0:10:58.33,0:11:02.32,Default,,0000,0000,0000,,and that the tissue organization is dependent
Dialogue: 0,0:11:02.32,0:11:06.02,Default,,0000,0000,0000,,on the extracellular matrix and the microenvironment.
Dialogue: 0,0:11:06.02,0:11:13.65,Default,,0000,0000,0000,,All right, thus form and function interact dynamically and reciprocally.
Dialogue: 0,0:11:13.65,0:11:17.77,Default,,0000,0000,0000,,And here is another five seconds of repose,
Dialogue: 0,0:11:17.77,0:11:22.19,Default,,0000,0000,0000,,is my mantra. Form and function.
Dialogue: 0,0:11:22.19,0:11:25.84,Default,,0000,0000,0000,,And of course, we now ask, where do we go now?
Dialogue: 0,0:11:25.84,0:11:28.83,Default,,0000,0000,0000,,We'd like to take this kind of thinking into the clinic.
Dialogue: 0,0:11:28.83,0:11:32.76,Default,,0000,0000,0000,,But before we do that, I'd like you to think
Dialogue: 0,0:11:32.76,0:11:36.34,Default,,0000,0000,0000,,that at any given time when you're sitting there,
Dialogue: 0,0:11:36.34,0:11:39.36,Default,,0000,0000,0000,,in your 70 trillion cells,
Dialogue: 0,0:11:39.36,0:11:42.83,Default,,0000,0000,0000,,the extracellular matrix signaling to your nucleus,
Dialogue: 0,0:11:42.83,0:11:45.91,Default,,0000,0000,0000,,the nucleus is signaling to your extracellular matrix
Dialogue: 0,0:11:45.91,0:11:51.90,Default,,0000,0000,0000,,and this is how your balance is kept and restored.
Dialogue: 0,0:11:51.90,0:11:54.12,Default,,0000,0000,0000,,We have made a lot of discoveries,
Dialogue: 0,0:11:54.12,0:11:57.20,Default,,0000,0000,0000,,we have shown that extracellular matrix talks to chromatin.
Dialogue: 0,0:11:57.20,0:12:00.65,Default,,0000,0000,0000,,We have shown that there's little pieces of DNA
Dialogue: 0,0:12:00.65,0:12:04.48,Default,,0000,0000,0000,,on the specific genes of the mammary gland
Dialogue: 0,0:12:04.48,0:12:07.34,Default,,0000,0000,0000,,that actually respond to extracellular matrix.
Dialogue: 0,0:12:07.34,0:12:11.04,Default,,0000,0000,0000,,It has taken many years, but it has been very rewarding.
Dialogue: 0,0:12:11.04,0:12:15.43,Default,,0000,0000,0000,,And before I get to the next slide, I have to tell you
Dialogue: 0,0:12:15.43,0:12:20.54,Default,,0000,0000,0000,,that there are so many additional discoveries to be made.
Dialogue: 0,0:12:20.54,0:12:23.07,Default,,0000,0000,0000,,There is so much mystery we don't know.
Dialogue: 0,0:12:23.07,0:12:27.43,Default,,0000,0000,0000,,And I always say to the students and post-docs I lecture to,
Dialogue: 0,0:12:27.43,0:12:33.09,Default,,0000,0000,0000,,don't be arrogant, because arrogance kills curiosity.
Dialogue: 0,0:12:33.09,0:12:35.28,Default,,0000,0000,0000,,Curiosity and passion.
Dialogue: 0,0:12:35.28,0:12:39.18,Default,,0000,0000,0000,,You need to always think, what else needs to be discovered?
Dialogue: 0,0:12:39.18,0:12:42.16,Default,,0000,0000,0000,,And maybe my discovery needs to be added to
Dialogue: 0,0:12:42.16,0:12:43.95,Default,,0000,0000,0000,,or maybe it needs to be changed.
Dialogue: 0,0:12:43.95,0:12:47.45,Default,,0000,0000,0000,,So, we have now made an amazing discovery,
Dialogue: 0,0:12:47.45,0:12:50.56,Default,,0000,0000,0000,,a post-doc in the lab who is a physicist asked me,
Dialogue: 0,0:12:50.56,0:12:52.73,Default,,0000,0000,0000,,what do the cells do when you put them in?
Dialogue: 0,0:12:52.73,0:12:56.03,Default,,0000,0000,0000,,What do they do in the beginning when they do?
Dialogue: 0,0:12:56.03,0:12:57.51,Default,,0000,0000,0000,,I said, I don't know, we couldn't look at them.
Dialogue: 0,0:12:57.51,0:13:00.10,Default,,0000,0000,0000,,We didn't have high images in the old days.
Dialogue: 0,0:13:00.10,0:13:02.80,Default,,0000,0000,0000,,So she, being an imager and a physicist,
Dialogue: 0,0:13:02.80,0:13:04.54,Default,,0000,0000,0000,,did this incredible thing.
Dialogue: 0,0:13:04.54,0:13:08.92,Default,,0000,0000,0000,,This is a single human breast cell in three dimensions.
Dialogue: 0,0:13:08.92,0:13:11.44,Default,,0000,0000,0000,,Look at it. It's constantly doing this.
Dialogue: 0,0:13:11.44,0:13:13.54,Default,,0000,0000,0000,,Has a coherent movement.
Dialogue: 0,0:13:13.54,0:13:17.87,Default,,0000,0000,0000,,You put the cancer cells there, and they do go all over,
Dialogue: 0,0:13:17.87,0:13:19.78,Default,,0000,0000,0000,,they do this. They don't do this.
Dialogue: 0,0:13:19.78,0:13:23.78,Default,,0000,0000,0000,,And when we revert the cancer cell, it again does this.
Dialogue: 0,0:13:23.78,0:13:25.97,Default,,0000,0000,0000,,Absolutely boggles my mind.
Dialogue: 0,0:13:25.97,0:13:31.31,Default,,0000,0000,0000,,So the cell acts like an embryo. What an exciting thing.
Dialogue: 0,0:13:31.31,0:13:34.17,Default,,0000,0000,0000,,So I'd like to finish with a poem.
Dialogue: 0,0:13:34.17,0:13:37.23,Default,,0000,0000,0000,,Well I used to love English literature,
Dialogue: 0,0:13:37.23,0:13:39.84,Default,,0000,0000,0000,,and I debated in college, which one should I do?
Dialogue: 0,0:13:39.84,0:13:44.45,Default,,0000,0000,0000,,And unfortunately or fortunately, chemistry won.
Dialogue: 0,0:13:44.45,0:13:50.18,Default,,0000,0000,0000,,But here is a poem from Yeats. I'll just read you the last two lines.
Dialogue: 0,0:13:50.18,0:13:52.84,Default,,0000,0000,0000,,It's called "Among the School Children."
Dialogue: 0,0:13:52.84,0:13:57.36,Default,,0000,0000,0000,,"O body swayed to music / O brightening glance /
Dialogue: 0,0:13:57.36,0:14:00.51,Default,,0000,0000,0000,,How [can we know] the dancer from the dance?"
Dialogue: 0,0:14:00.51,0:14:02.42,Default,,0000,0000,0000,,And here is Merce Cunningham,
Dialogue: 0,0:14:02.42,0:14:05.40,Default,,0000,0000,0000,,I was fortunate to dance with him when I was younger,
Dialogue: 0,0:14:05.40,0:14:07.59,Default,,0000,0000,0000,,and here he is a dancer,
Dialogue: 0,0:14:07.59,0:14:10.90,Default,,0000,0000,0000,,and while he is dancing, he is both the dancer and the dance.
Dialogue: 0,0:14:10.90,0:14:14.60,Default,,0000,0000,0000,,The minute he stops, we have neither.
Dialogue: 0,0:14:14.60,0:14:18.07,Default,,0000,0000,0000,,So it's like form and function.
Dialogue: 0,0:14:18.07,0:14:23.85,Default,,0000,0000,0000,,Now, I'd like to show you a current picture of my group.
Dialogue: 0,0:14:23.85,0:14:27.38,Default,,0000,0000,0000,,I have been fortunate to have had these magnificant
Dialogue: 0,0:14:27.38,0:14:30.60,Default,,0000,0000,0000,,students and post-docs who have taught me so much,
Dialogue: 0,0:14:30.60,0:14:33.87,Default,,0000,0000,0000,,and I have had many of these groups come and go.
Dialogue: 0,0:14:33.87,0:14:38.44,Default,,0000,0000,0000,,They are the future and I try to make them not be afraid
Dialogue: 0,0:14:38.44,0:14:42.15,Default,,0000,0000,0000,,of being the cat and being told,
Dialogue: 0,0:14:42.15,0:14:43.74,Default,,0000,0000,0000,,don't think outside the box.
Dialogue: 0,0:14:43.74,0:14:46.24,Default,,0000,0000,0000,,And I'd like to leave you with this thought.
Dialogue: 0,0:14:46.24,0:14:50.98,Default,,0000,0000,0000,,On the left is water coming through the shore,
Dialogue: 0,0:14:50.98,0:14:52.88,Default,,0000,0000,0000,,taken from a NASA satellite.
Dialogue: 0,0:14:52.88,0:14:55.92,Default,,0000,0000,0000,,On the right, there is a coral.
Dialogue: 0,0:14:55.92,0:14:59.93,Default,,0000,0000,0000,,Now if you take the mammary gland and spread it
Dialogue: 0,0:14:59.93,0:15:03.37,Default,,0000,0000,0000,,and take the fat away, on a dish it looks like that.
Dialogue: 0,0:15:03.37,0:15:06.72,Default,,0000,0000,0000,,Do they look the same? Do they have the same patterns?
Dialogue: 0,0:15:06.72,0:15:10.68,Default,,0000,0000,0000,,Why is it that nature keeps doing that over and over again?
Dialogue: 0,0:15:10.68,0:15:13.04,Default,,0000,0000,0000,,And I'd like to submit to you
Dialogue: 0,0:15:13.04,0:15:15.21,Default,,0000,0000,0000,,that we have sequenced the human genome,
Dialogue: 0,0:15:15.21,0:15:18.09,Default,,0000,0000,0000,,we know everything about the sequence of the gene,
Dialogue: 0,0:15:18.09,0:15:20.52,Default,,0000,0000,0000,,the language of the gene, the alphabet of the gene,
Dialogue: 0,0:15:20.52,0:15:23.76,Default,,0000,0000,0000,,But we know nothing, but nothing,
Dialogue: 0,0:15:23.76,0:15:28.42,Default,,0000,0000,0000,,about the language and alphabet of form.
Dialogue: 0,0:15:28.42,0:15:31.47,Default,,0000,0000,0000,,So, it's a wonderful new horizon,
Dialogue: 0,0:15:31.47,0:15:35.22,Default,,0000,0000,0000,,it's a wonderful thing to discover for the young
Dialogue: 0,0:15:35.22,0:15:37.70,Default,,0000,0000,0000,,and the passionate old, and that's me.
Dialogue: 0,0:15:37.70,0:15:39.75,Default,,0000,0000,0000,,So go to it!
Dialogue: 0,0:15:39.75,0:15:51.25,Default,,0000,0000,0000,,(Applause)