[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:10.77,0:00:14.06,Default,,0000,0000,0000,,I moved to Boston\N10 years ago from Chicago,
Dialogue: 0,0:00:14.08,0:00:16.68,Default,,0000,0000,0000,,with an interest in cancer\Nand in chemistry.
Dialogue: 0,0:00:17.17,0:00:20.47,Default,,0000,0000,0000,,You might know that chemistry\Nis the science of making molecules
Dialogue: 0,0:00:20.49,0:00:21.81,Default,,0000,0000,0000,,or, to my taste,
Dialogue: 0,0:00:21.83,0:00:23.46,Default,,0000,0000,0000,,new drugs for cancer.
Dialogue: 0,0:00:23.78,0:00:26.58,Default,,0000,0000,0000,,And you might also know that,\Nfor science and medicine,
Dialogue: 0,0:00:26.60,0:00:29.01,Default,,0000,0000,0000,,Boston is a bit of a candy store.
Dialogue: 0,0:00:30.61,0:00:35.23,Default,,0000,0000,0000,,You can't roll a stop sign in Cambridge\Nwithout hitting a graduate student.
Dialogue: 0,0:00:35.25,0:00:37.43,Default,,0000,0000,0000,,The bar is called the Miracle of Science.
Dialogue: 0,0:00:37.83,0:00:40.70,Default,,0000,0000,0000,,The billboards say "Lab Space Available."
Dialogue: 0,0:00:40.90,0:00:43.06,Default,,0000,0000,0000,,And it's fair to say\Nthat in these 10 years,
Dialogue: 0,0:00:43.08,0:00:47.39,Default,,0000,0000,0000,,we've witnessed absolutely the start\Nof a scientific revolution --
Dialogue: 0,0:00:47.41,0:00:48.89,Default,,0000,0000,0000,,that of genome medicine.
Dialogue: 0,0:00:49.58,0:00:52.30,Default,,0000,0000,0000,,We know more about the patients\Nthat enter our clinic now
Dialogue: 0,0:00:52.33,0:00:53.49,Default,,0000,0000,0000,,than ever before.
Dialogue: 0,0:00:53.51,0:00:55.74,Default,,0000,0000,0000,,And we're able, finally,\Nto answer the question
Dialogue: 0,0:00:55.76,0:00:58.12,Default,,0000,0000,0000,,that's been so pressing for so many years:
Dialogue: 0,0:00:58.15,0:01:00.10,Default,,0000,0000,0000,,Why do I have cancer?
Dialogue: 0,0:01:01.22,0:01:03.34,Default,,0000,0000,0000,,This information\Nis also pretty staggering.
Dialogue: 0,0:01:03.76,0:01:06.85,Default,,0000,0000,0000,,You might know that, so far,\Nin just the dawn of this revolution,
Dialogue: 0,0:01:06.87,0:01:10.60,Default,,0000,0000,0000,,we know that there are perhaps\N40,000 unique mutations
Dialogue: 0,0:01:10.62,0:01:13.23,Default,,0000,0000,0000,,affecting more than 10,000 genes,
Dialogue: 0,0:01:13.26,0:01:16.62,Default,,0000,0000,0000,,and that there are 500 of these genes\Nthat are bona-fide drivers,
Dialogue: 0,0:01:16.64,0:01:18.54,Default,,0000,0000,0000,,causes of cancer.
Dialogue: 0,0:01:19.63,0:01:20.83,Default,,0000,0000,0000,,Yet comparatively,
Dialogue: 0,0:01:20.85,0:01:23.62,Default,,0000,0000,0000,,we have about a dozen\Ntargeted medications.
Dialogue: 0,0:01:24.51,0:01:26.77,Default,,0000,0000,0000,,And this inadequacy of cancer medicine
Dialogue: 0,0:01:26.80,0:01:30.91,Default,,0000,0000,0000,,really hit home when my father\Nwas diagnosed with pancreatic cancer.
Dialogue: 0,0:01:32.75,0:01:34.41,Default,,0000,0000,0000,,We didn't fly him to Boston.
Dialogue: 0,0:01:34.44,0:01:35.97,Default,,0000,0000,0000,,We didn't sequence his genome.
Dialogue: 0,0:01:36.35,0:01:39.49,Default,,0000,0000,0000,,It's been known for decades\Nwhat causes this malignancy.
Dialogue: 0,0:01:40.90,0:01:44.95,Default,,0000,0000,0000,,It's three proteins: ras, myc, p53.
Dialogue: 0,0:01:46.38,0:01:49.08,Default,,0000,0000,0000,,This is old information\Nwe've known since about the 80s,
Dialogue: 0,0:01:49.10,0:01:51.02,Default,,0000,0000,0000,,yet there's no medicine I can prescribe
Dialogue: 0,0:01:51.04,0:01:54.61,Default,,0000,0000,0000,,to a patient with this\Nor any of the numerous solid tumors
Dialogue: 0,0:01:54.63,0:01:56.32,Default,,0000,0000,0000,,caused by these three ...
Dialogue: 0,0:01:57.28,0:01:59.59,Default,,0000,0000,0000,,Horsemen of the Apocalypse that is cancer.
Dialogue: 0,0:01:59.98,0:02:02.42,Default,,0000,0000,0000,,There's no ras, no myc, no p53 drug.
Dialogue: 0,0:02:02.80,0:02:05.05,Default,,0000,0000,0000,,And you might fairly ask: Why is that?
Dialogue: 0,0:02:05.75,0:02:08.58,Default,,0000,0000,0000,,And the very unsatisfying\Nyet scientific answer is:
Dialogue: 0,0:02:08.61,0:02:09.76,Default,,0000,0000,0000,,it's too hard.
Dialogue: 0,0:02:10.32,0:02:11.59,Default,,0000,0000,0000,,That for whatever reason,
Dialogue: 0,0:02:11.61,0:02:15.11,Default,,0000,0000,0000,,these three proteins have entered\Na space, in the language of our field,
Dialogue: 0,0:02:15.13,0:02:17.33,Default,,0000,0000,0000,,that's called the undruggable genome --
Dialogue: 0,0:02:17.36,0:02:19.64,Default,,0000,0000,0000,,which is like calling\Na computer unsurfable
Dialogue: 0,0:02:19.67,0:02:20.92,Default,,0000,0000,0000,,or the Moon unwalkable.
Dialogue: 0,0:02:20.95,0:02:23.06,Default,,0000,0000,0000,,It's a horrible term of trade.
Dialogue: 0,0:02:23.08,0:02:24.24,Default,,0000,0000,0000,,But what it means
Dialogue: 0,0:02:24.26,0:02:27.48,Default,,0000,0000,0000,,is that we've failed to identify\Na greasy pocket in these proteins,
Dialogue: 0,0:02:27.51,0:02:29.78,Default,,0000,0000,0000,,into which we, like molecular locksmiths,
Dialogue: 0,0:02:29.80,0:02:34.90,Default,,0000,0000,0000,,can fashion an active, small,\Norganic molecule or drug substance.
Dialogue: 0,0:02:35.47,0:02:37.91,Default,,0000,0000,0000,,Now, as I was training\Nin clinical medicine
Dialogue: 0,0:02:37.93,0:02:41.39,Default,,0000,0000,0000,,and hematology and oncology\Nand stem-cell transplantation,
Dialogue: 0,0:02:41.42,0:02:43.29,Default,,0000,0000,0000,,what we had instead,
Dialogue: 0,0:02:43.81,0:02:48.70,Default,,0000,0000,0000,,cascading through the regulatory\Nnetwork at the FDA,
Dialogue: 0,0:02:48.75,0:02:50.18,Default,,0000,0000,0000,,were these substances:
Dialogue: 0,0:02:50.21,0:02:51.52,Default,,0000,0000,0000,,arsenic,
Dialogue: 0,0:02:51.54,0:02:52.71,Default,,0000,0000,0000,,thalidomide,
Dialogue: 0,0:02:52.73,0:02:56.09,Default,,0000,0000,0000,,and this chemical derivative\Nof nitrogen mustard gas.
Dialogue: 0,0:02:56.11,0:02:58.72,Default,,0000,0000,0000,,And this is the 21st century.
Dialogue: 0,0:02:59.24,0:03:00.49,Default,,0000,0000,0000,,And so, I guess you'd say,
Dialogue: 0,0:03:00.52,0:03:03.65,Default,,0000,0000,0000,,dissatisfied with the performance\Nand quality of these medicines,
Dialogue: 0,0:03:03.68,0:03:05.95,Default,,0000,0000,0000,,I went back to school, in chemistry,
Dialogue: 0,0:03:07.55,0:03:12.90,Default,,0000,0000,0000,,with the idea that perhaps by learning\Nthe trade of discovery chemistry
Dialogue: 0,0:03:12.93,0:03:15.80,Default,,0000,0000,0000,,and approaching it in the context\Nof this brave new world
Dialogue: 0,0:03:15.83,0:03:18.04,Default,,0000,0000,0000,,of the open source,
Dialogue: 0,0:03:18.06,0:03:19.49,Default,,0000,0000,0000,,the crowd source,
Dialogue: 0,0:03:19.52,0:03:22.82,Default,,0000,0000,0000,,the collaborative network\Nthat we have access to within academia,
Dialogue: 0,0:03:22.85,0:03:27.12,Default,,0000,0000,0000,,that we might more quickly bring\Npowerful and targeted therapies
Dialogue: 0,0:03:27.15,0:03:28.51,Default,,0000,0000,0000,,to our patients.
Dialogue: 0,0:03:28.89,0:03:31.99,Default,,0000,0000,0000,,And so, please consider\Nthis a work in progress,
Dialogue: 0,0:03:32.02,0:03:34.03,Default,,0000,0000,0000,,but I'd like to tell you today a story
Dialogue: 0,0:03:34.06,0:03:37.26,Default,,0000,0000,0000,,about a very rare cancer\Ncalled midline carcinoma,
Dialogue: 0,0:03:38.06,0:03:42.27,Default,,0000,0000,0000,,about the undruggable protein target\Nthat causes this cancer,
Dialogue: 0,0:03:42.30,0:03:43.82,Default,,0000,0000,0000,,called BRD4,
Dialogue: 0,0:03:44.15,0:03:47.99,Default,,0000,0000,0000,,and about a molecule developed at my lab\Nat Dana-Farber Cancer Institute,
Dialogue: 0,0:03:48.02,0:03:49.17,Default,,0000,0000,0000,,called JQ1,
Dialogue: 0,0:03:49.19,0:03:51.42,Default,,0000,0000,0000,,which we affectionately named for Jun Qi,
Dialogue: 0,0:03:51.44,0:03:53.48,Default,,0000,0000,0000,,the chemist that made this molecule.
Dialogue: 0,0:03:54.41,0:03:57.10,Default,,0000,0000,0000,,Now, BRD4 is an interesting protein.
Dialogue: 0,0:03:57.13,0:04:00.81,Default,,0000,0000,0000,,You might ask: with all the things\Ncancer's trying to do to kill our patient,
Dialogue: 0,0:04:00.83,0:04:02.42,Default,,0000,0000,0000,,how does it remember it's cancer?
Dialogue: 0,0:04:02.45,0:04:03.88,Default,,0000,0000,0000,,When it winds up its genome,
Dialogue: 0,0:04:03.90,0:04:06.27,Default,,0000,0000,0000,,divides into two cells and unwinds again,
Dialogue: 0,0:04:06.30,0:04:08.53,Default,,0000,0000,0000,,why does it not turn\Ninto an eye, into a liver,
Dialogue: 0,0:04:08.56,0:04:10.94,Default,,0000,0000,0000,,as it has all the genes\Nnecessary to do this?
Dialogue: 0,0:04:10.96,0:04:12.52,Default,,0000,0000,0000,,It remembers that it's cancer.
Dialogue: 0,0:04:13.39,0:04:16.48,Default,,0000,0000,0000,,And the reason is that cancer,\Nlike every cell in the body,
Dialogue: 0,0:04:16.50,0:04:18.48,Default,,0000,0000,0000,,places little molecular bookmarks,
Dialogue: 0,0:04:18.50,0:04:19.88,Default,,0000,0000,0000,,little Post-it notes,
Dialogue: 0,0:04:19.90,0:04:22.88,Default,,0000,0000,0000,,that remind the cell, "I'm cancer;\NI should keep growing."
Dialogue: 0,0:04:23.50,0:04:27.51,Default,,0000,0000,0000,,And those Post-it notes involve this\Nand other proteins of its class --
Dialogue: 0,0:04:27.54,0:04:28.85,Default,,0000,0000,0000,,so-called bromodomains.
Dialogue: 0,0:04:29.43,0:04:32.10,Default,,0000,0000,0000,,So we developed an idea, a rationale,
Dialogue: 0,0:04:32.12,0:04:34.27,Default,,0000,0000,0000,,that perhaps if we made a molecule
Dialogue: 0,0:04:34.30,0:04:36.59,Default,,0000,0000,0000,,that prevented\Nthe Post-it note from sticking
Dialogue: 0,0:04:36.61,0:04:38.27,Default,,0000,0000,0000,,by entering into the little pocket
Dialogue: 0,0:04:38.30,0:04:40.15,Default,,0000,0000,0000,,at the base of this spinning protein,
Dialogue: 0,0:04:40.18,0:04:42.23,Default,,0000,0000,0000,,then maybe we could convince cancer cells,
Dialogue: 0,0:04:42.26,0:04:45.06,Default,,0000,0000,0000,,certainly those addicted\Nto this BRD4 protein,
Dialogue: 0,0:04:45.08,0:04:46.40,Default,,0000,0000,0000,,that they're not cancer.
Dialogue: 0,0:04:47.12,0:04:49.34,Default,,0000,0000,0000,,And so we started to work on this problem.
Dialogue: 0,0:04:49.36,0:04:51.67,Default,,0000,0000,0000,,We developed libraries of compounds
Dialogue: 0,0:04:51.69,0:04:54.48,Default,,0000,0000,0000,,and eventually arrived\Nat this and similar substances
Dialogue: 0,0:04:54.50,0:04:55.68,Default,,0000,0000,0000,,called JQ1.
Dialogue: 0,0:04:56.28,0:04:57.84,Default,,0000,0000,0000,,Now, not being a drug company,
Dialogue: 0,0:04:57.86,0:05:00.96,Default,,0000,0000,0000,,we could do certain things,\Nwe had certain flexibilities,
Dialogue: 0,0:05:00.98,0:05:03.82,Default,,0000,0000,0000,,that I respect that a pharmaceutical\Nindustry doesn't have.
Dialogue: 0,0:05:03.84,0:05:06.09,Default,,0000,0000,0000,,We just started mailing it to our friends.
Dialogue: 0,0:05:06.58,0:05:07.74,Default,,0000,0000,0000,,I have a small lab.
Dialogue: 0,0:05:07.76,0:05:11.16,Default,,0000,0000,0000,,We thought we'd just send it to people\Nand see how the molecule behaves.
Dialogue: 0,0:05:11.19,0:05:12.64,Default,,0000,0000,0000,,We sent it to Oxford, England,
Dialogue: 0,0:05:12.66,0:05:15.88,Default,,0000,0000,0000,,where a group of talented\Ncrystallographers provided this picture,
Dialogue: 0,0:05:15.91,0:05:19.01,Default,,0000,0000,0000,,which helped us understand exactly\Nhow this molecule is so potent
Dialogue: 0,0:05:19.03,0:05:20.20,Default,,0000,0000,0000,,for this protein target.
Dialogue: 0,0:05:20.22,0:05:23.16,Default,,0000,0000,0000,,It's what we call a perfect fit\Nof shape complementarity,
Dialogue: 0,0:05:23.18,0:05:24.33,Default,,0000,0000,0000,,or hand in glove.
Dialogue: 0,0:05:25.03,0:05:26.65,Default,,0000,0000,0000,,Now, this is a very rare cancer,
Dialogue: 0,0:05:26.67,0:05:28.48,Default,,0000,0000,0000,,this BRD4-addicted cancer.
Dialogue: 0,0:05:28.90,0:05:31.13,Default,,0000,0000,0000,,And so we worked with samples of material
Dialogue: 0,0:05:31.16,0:05:34.73,Default,,0000,0000,0000,,that were collected by young pathologists\Nat Brigham and Women's Hospital.
Dialogue: 0,0:05:34.75,0:05:37.13,Default,,0000,0000,0000,,And as we treated these cells\Nwith this molecule,
Dialogue: 0,0:05:37.15,0:05:39.19,Default,,0000,0000,0000,,we observed something really striking.
Dialogue: 0,0:05:39.50,0:05:40.71,Default,,0000,0000,0000,,The cancer cells --
Dialogue: 0,0:05:40.73,0:05:42.80,Default,,0000,0000,0000,,small, round and rapidly dividing,
Dialogue: 0,0:05:42.82,0:05:45.17,Default,,0000,0000,0000,,grew these arms and extensions.
Dialogue: 0,0:05:45.20,0:05:46.56,Default,,0000,0000,0000,,They were changing shape.
Dialogue: 0,0:05:47.02,0:05:48.35,Default,,0000,0000,0000,,In effect,
Dialogue: 0,0:05:48.37,0:05:51.68,Default,,0000,0000,0000,,the cancer cell\Nwas forgetting it was cancer
Dialogue: 0,0:05:51.70,0:05:53.21,Default,,0000,0000,0000,,and becoming a normal cell.
Dialogue: 0,0:05:54.78,0:05:56.13,Default,,0000,0000,0000,,This got us very excited.
Dialogue: 0,0:05:57.54,0:06:00.13,Default,,0000,0000,0000,,The next step would be to put\Nthis molecule into mice.
Dialogue: 0,0:06:00.15,0:06:03.55,Default,,0000,0000,0000,,The only problem was there's no\Nmouse model of this rare cancer.
Dialogue: 0,0:06:03.57,0:06:06.30,Default,,0000,0000,0000,,And so at the time\Nwe were doing this research,
Dialogue: 0,0:06:06.32,0:06:09.89,Default,,0000,0000,0000,,I was caring for a 29-year-old\Nfirefighter from Connecticut
Dialogue: 0,0:06:09.92,0:06:11.80,Default,,0000,0000,0000,,who was very much at the end of life
Dialogue: 0,0:06:11.82,0:06:13.68,Default,,0000,0000,0000,,with this incurable cancer.
Dialogue: 0,0:06:14.32,0:06:17.77,Default,,0000,0000,0000,,This BRD4-addicted cancer\Nwas growing throughout his left lung.
Dialogue: 0,0:06:17.80,0:06:20.96,Default,,0000,0000,0000,,And he had a chest tube in\Nthat was draining little bits of debris.
Dialogue: 0,0:06:20.98,0:06:23.94,Default,,0000,0000,0000,,And every nursing shift,\Nwe would throw this material out.
Dialogue: 0,0:06:23.97,0:06:25.74,Default,,0000,0000,0000,,And so we approached this patient
Dialogue: 0,0:06:25.76,0:06:27.77,Default,,0000,0000,0000,,and asked if he would collaborate with us.
Dialogue: 0,0:06:28.42,0:06:32.11,Default,,0000,0000,0000,,Could we take this precious\Nand rare cancerous material
Dialogue: 0,0:06:32.14,0:06:33.74,Default,,0000,0000,0000,,from this chest tube
Dialogue: 0,0:06:33.76,0:06:35.98,Default,,0000,0000,0000,,and drive it across town\Nand put it into mice
Dialogue: 0,0:06:36.00,0:06:39.64,Default,,0000,0000,0000,,and try to do a clinical trial\Nat a stage that with a prototype drug,
Dialogue: 0,0:06:39.67,0:06:41.69,Default,,0000,0000,0000,,well, that would be, of course, impossible
Dialogue: 0,0:06:41.72,0:06:43.55,Default,,0000,0000,0000,,and, rightly, illegal to do in humans.
Dialogue: 0,0:06:43.57,0:06:44.83,Default,,0000,0000,0000,,And he obliged us.
Dialogue: 0,0:06:45.71,0:06:49.45,Default,,0000,0000,0000,,At the Lurie Family Center\Nfor Animal Imaging,
Dialogue: 0,0:06:49.52,0:06:53.14,Default,,0000,0000,0000,,our colleague, Andrew Kung,\Ngrew this cancer successfully in mice
Dialogue: 0,0:06:53.16,0:06:54.85,Default,,0000,0000,0000,,without ever touching plastic.
Dialogue: 0,0:06:55.18,0:06:58.59,Default,,0000,0000,0000,,And you can see this PET scan\Nof a mouse -- what we call a pet PET.
Dialogue: 0,0:06:58.62,0:07:00.17,Default,,0000,0000,0000,,The cancer is growing
Dialogue: 0,0:07:00.20,0:07:03.10,Default,,0000,0000,0000,,as this red, huge mass\Nin the hind limb of this animal.
Dialogue: 0,0:07:03.52,0:07:05.74,Default,,0000,0000,0000,,And as we treat it with our compound,
Dialogue: 0,0:07:05.77,0:07:07.38,Default,,0000,0000,0000,,this addiction to sugar,
Dialogue: 0,0:07:07.40,0:07:08.99,Default,,0000,0000,0000,,this rapid growth, faded.
Dialogue: 0,0:07:09.02,0:07:11.06,Default,,0000,0000,0000,,And on the animal on the right,
Dialogue: 0,0:07:11.08,0:07:13.09,Default,,0000,0000,0000,,you see that the cancer was responding.
Dialogue: 0,0:07:14.17,0:07:16.38,Default,,0000,0000,0000,,We've completed, now, clinical trials
Dialogue: 0,0:07:16.40,0:07:18.38,Default,,0000,0000,0000,,in four mouse models of this disease.
Dialogue: 0,0:07:18.40,0:07:20.25,Default,,0000,0000,0000,,And every time, we see the same thing.
Dialogue: 0,0:07:20.27,0:07:22.98,Default,,0000,0000,0000,,The mice with this cancer\Nthat get the drug live,
Dialogue: 0,0:07:23.00,0:07:25.30,Default,,0000,0000,0000,,and the ones that don't rapidly perish.
Dialogue: 0,0:07:27.40,0:07:28.83,Default,,0000,0000,0000,,So we started to wonder,
Dialogue: 0,0:07:28.85,0:07:30.96,Default,,0000,0000,0000,,what would a drug company\Ndo at this point?
Dialogue: 0,0:07:30.98,0:07:33.03,Default,,0000,0000,0000,,Well, they probably\Nwould keep this a secret
Dialogue: 0,0:07:33.05,0:07:34.94,Default,,0000,0000,0000,,until they turn the prototype drug
Dialogue: 0,0:07:34.96,0:07:37.11,Default,,0000,0000,0000,,into an active pharmaceutical substance.
Dialogue: 0,0:07:37.66,0:07:39.10,Default,,0000,0000,0000,,So we did just the opposite.
Dialogue: 0,0:07:39.48,0:07:42.32,Default,,0000,0000,0000,,We published a paper\Nthat described this finding
Dialogue: 0,0:07:42.34,0:07:44.32,Default,,0000,0000,0000,,at the earliest prototype stage.
Dialogue: 0,0:07:45.11,0:07:48.02,Default,,0000,0000,0000,,We gave the world the chemical\Nidentity of this molecule,
Dialogue: 0,0:07:48.04,0:07:49.94,Default,,0000,0000,0000,,typically a secret in our discipline.
Dialogue: 0,0:07:49.97,0:07:51.94,Default,,0000,0000,0000,,We told people exactly how to make it.
Dialogue: 0,0:07:52.64,0:07:54.31,Default,,0000,0000,0000,,We gave them our email address,
Dialogue: 0,0:07:54.33,0:07:55.98,Default,,0000,0000,0000,,suggesting that if they write us,
Dialogue: 0,0:07:56.01,0:07:57.61,Default,,0000,0000,0000,,we'll send them a free molecule.
Dialogue: 0,0:07:57.63,0:07:58.72,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:07:58.74,0:08:01.64,Default,,0000,0000,0000,,We basically tried to create\Nthe most competitive environment
Dialogue: 0,0:08:01.66,0:08:02.82,Default,,0000,0000,0000,,for our lab as possible.
Dialogue: 0,0:08:02.85,0:08:04.79,Default,,0000,0000,0000,,And this was, unfortunately, successful.
Dialogue: 0,0:08:04.82,0:08:05.84,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:08:05.86,0:08:07.87,Default,,0000,0000,0000,,Because now, we've shared this molecule,
Dialogue: 0,0:08:07.89,0:08:10.30,Default,,0000,0000,0000,,just since December of last year,
Dialogue: 0,0:08:10.32,0:08:12.57,Default,,0000,0000,0000,,with 40 laboratories in the United States
Dialogue: 0,0:08:12.60,0:08:14.38,Default,,0000,0000,0000,,and 30 more in Europe --
Dialogue: 0,0:08:14.40,0:08:16.25,Default,,0000,0000,0000,,many of them pharmaceutical companies,
Dialogue: 0,0:08:16.27,0:08:17.87,Default,,0000,0000,0000,,seeking now to enter this space,
Dialogue: 0,0:08:17.89,0:08:20.94,Default,,0000,0000,0000,,to target this rare cancer\Nthat, thankfully right now,
Dialogue: 0,0:08:21.80,0:08:24.41,Default,,0000,0000,0000,,is quite desirable\Nto study in that industry.
Dialogue: 0,0:08:26.66,0:08:29.73,Default,,0000,0000,0000,,But the science that's coming back\Nfrom all of these laboratories
Dialogue: 0,0:08:29.76,0:08:31.59,Default,,0000,0000,0000,,about the use of this molecule
Dialogue: 0,0:08:31.61,0:08:34.78,Default,,0000,0000,0000,,has provided us insights\Nwe might not have had on our own.
Dialogue: 0,0:08:34.81,0:08:36.79,Default,,0000,0000,0000,,Leukemia cells treated with this compound
Dialogue: 0,0:08:36.81,0:08:39.23,Default,,0000,0000,0000,,turn into normal white blood cells.
Dialogue: 0,0:08:39.88,0:08:41.66,Default,,0000,0000,0000,,Mice with multiple myeloma,
Dialogue: 0,0:08:41.68,0:08:44.72,Default,,0000,0000,0000,,an incurable malignancy\Nof the bone marrow,
Dialogue: 0,0:08:45.74,0:08:47.72,Default,,0000,0000,0000,,respond dramatically
Dialogue: 0,0:08:47.74,0:08:49.46,Default,,0000,0000,0000,,to the treatment with this drug.
Dialogue: 0,0:08:50.22,0:08:52.19,Default,,0000,0000,0000,,You might know that fat has memory.
Dialogue: 0,0:08:53.26,0:08:55.24,Default,,0000,0000,0000,,I'll nicely demonstrate that for you.
Dialogue: 0,0:08:55.26,0:08:56.30,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:08:56.32,0:08:57.87,Default,,0000,0000,0000,,In fact, this molecule
Dialogue: 0,0:08:57.90,0:09:01.30,Default,,0000,0000,0000,,prevents this adipocyte,\Nthis fat stem cell,
Dialogue: 0,0:09:01.32,0:09:04.19,Default,,0000,0000,0000,,from remembering how to make fat,
Dialogue: 0,0:09:04.21,0:09:06.58,Default,,0000,0000,0000,,such that mice on a high-fat diet,
Dialogue: 0,0:09:06.60,0:09:08.72,Default,,0000,0000,0000,,like the folks\Nin my hometown of Chicago --
Dialogue: 0,0:09:08.74,0:09:09.75,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:09:09.77,0:09:11.78,Default,,0000,0000,0000,,fail to develop fatty liver,
Dialogue: 0,0:09:11.81,0:09:13.63,Default,,0000,0000,0000,,which is a major medical problem.
Dialogue: 0,0:09:14.82,0:09:16.39,Default,,0000,0000,0000,,What this research taught us --
Dialogue: 0,0:09:16.42,0:09:18.68,Default,,0000,0000,0000,,not just my lab, but our institute,
Dialogue: 0,0:09:18.70,0:09:20.77,Default,,0000,0000,0000,,and Harvard Medical School\Nmore generally --
Dialogue: 0,0:09:20.80,0:09:23.06,Default,,0000,0000,0000,,is that we have unique\Nresources in academia
Dialogue: 0,0:09:23.08,0:09:24.42,Default,,0000,0000,0000,,for drug discovery;
Dialogue: 0,0:09:24.44,0:09:27.62,Default,,0000,0000,0000,,that our center, which has tested\Nperhaps more cancer molecules
Dialogue: 0,0:09:27.65,0:09:28.80,Default,,0000,0000,0000,,in a scientific way
Dialogue: 0,0:09:28.83,0:09:29.98,Default,,0000,0000,0000,,than any other,
Dialogue: 0,0:09:30.00,0:09:31.48,Default,,0000,0000,0000,,never made one of its own.
Dialogue: 0,0:09:32.44,0:09:34.61,Default,,0000,0000,0000,,For all the reasons you see listed here,
Dialogue: 0,0:09:34.64,0:09:37.38,Default,,0000,0000,0000,,we think there's a great\Nopportunity for academic centers
Dialogue: 0,0:09:37.40,0:09:41.22,Default,,0000,0000,0000,,to participate in this earliest,\Nconceptually tricky
Dialogue: 0,0:09:41.25,0:09:43.18,Default,,0000,0000,0000,,and creative discipline
Dialogue: 0,0:09:43.20,0:09:44.98,Default,,0000,0000,0000,,of prototype drug discovery.
Dialogue: 0,0:09:47.77,0:09:48.92,Default,,0000,0000,0000,,So what next?
Dialogue: 0,0:09:49.25,0:09:51.63,Default,,0000,0000,0000,,We have this molecule,\Nbut it's not a pill yet.
Dialogue: 0,0:09:51.65,0:09:54.25,Default,,0000,0000,0000,,It's not orally bioavailable.
Dialogue: 0,0:09:54.27,0:09:57.47,Default,,0000,0000,0000,,We need to fix it so we can\Ndeliver it to our patients.
Dialogue: 0,0:09:57.49,0:09:59.07,Default,,0000,0000,0000,,And everyone in the lab,
Dialogue: 0,0:09:59.10,0:10:01.90,Default,,0000,0000,0000,,especially following the interaction\Nwith these patients,
Dialogue: 0,0:10:01.92,0:10:04.25,Default,,0000,0000,0000,,feels quite compelled\Nto deliver a drug substance
Dialogue: 0,0:10:04.27,0:10:05.47,Default,,0000,0000,0000,,based on this molecule.
Dialogue: 0,0:10:05.99,0:10:07.40,Default,,0000,0000,0000,,It's here where I'd say
Dialogue: 0,0:10:07.43,0:10:09.64,Default,,0000,0000,0000,,that we could use your help\Nand your insights,
Dialogue: 0,0:10:09.67,0:10:11.53,Default,,0000,0000,0000,,your collaborative participation.
Dialogue: 0,0:10:12.48,0:10:16.16,Default,,0000,0000,0000,,Unlike a drug company,\Nwe don't have a pipeline
Dialogue: 0,0:10:16.19,0:10:18.19,Default,,0000,0000,0000,,that we can deposit these molecules into.
Dialogue: 0,0:10:18.22,0:10:20.61,Default,,0000,0000,0000,,We don't have a team\Nof salespeople and marketeers
Dialogue: 0,0:10:20.64,0:10:23.35,Default,,0000,0000,0000,,to tell us how to position\Nthis drug against the other.
Dialogue: 0,0:10:23.37,0:10:26.04,Default,,0000,0000,0000,,What we do have is the flexibility\Nof an academic center
Dialogue: 0,0:10:26.06,0:10:28.00,Default,,0000,0000,0000,,to work with competent, motivated,
Dialogue: 0,0:10:28.04,0:10:30.95,Default,,0000,0000,0000,,enthusiastic, hopefully well-funded people
Dialogue: 0,0:10:30.97,0:10:33.26,Default,,0000,0000,0000,,to carry these molecules\Nforward into the clinic
Dialogue: 0,0:10:33.29,0:10:36.98,Default,,0000,0000,0000,,while preserving our ability\Nto share the prototype drug worldwide.
Dialogue: 0,0:10:38.07,0:10:40.72,Default,,0000,0000,0000,,This molecule will soon leave our benches
Dialogue: 0,0:10:40.74,0:10:43.79,Default,,0000,0000,0000,,and go into a small start-up company\Ncalled Tensha Therapeutics.
Dialogue: 0,0:10:43.81,0:10:46.75,Default,,0000,0000,0000,,And, really, this is the fourth\Nof these molecules
Dialogue: 0,0:10:46.77,0:10:49.02,Default,,0000,0000,0000,,to kind of "graduate"\Nfrom our little pipeline
Dialogue: 0,0:10:49.04,0:10:50.50,Default,,0000,0000,0000,,of drug discovery,
Dialogue: 0,0:10:50.52,0:10:54.88,Default,,0000,0000,0000,,two of which -- a topical drug\Nfor lymphoma of the skin
Dialogue: 0,0:10:55.80,0:10:58.91,Default,,0000,0000,0000,,and an oral substance for the treatment\Nof multiple myeloma --
Dialogue: 0,0:10:58.93,0:11:02.17,Default,,0000,0000,0000,,will actually come to the bedside\Nfor the first clinical trial
Dialogue: 0,0:11:02.19,0:11:05.72,Default,,0000,0000,0000,,in July of this year -- for us,\Na major and exciting milestone.
Dialogue: 0,0:11:07.15,0:11:09.17,Default,,0000,0000,0000,,I want to leave you with just two ideas.
Dialogue: 0,0:11:09.20,0:11:13.53,Default,,0000,0000,0000,,The first is: if anything is unique\Nabout this research,
Dialogue: 0,0:11:13.55,0:11:15.91,Default,,0000,0000,0000,,it's less the science than the strategy.
Dialogue: 0,0:11:15.94,0:11:18.36,Default,,0000,0000,0000,,This, for us, was a social experiment --
Dialogue: 0,0:11:18.38,0:11:23.65,Default,,0000,0000,0000,,an experiment in "What would happen\Nif we were as open and honest
Dialogue: 0,0:11:23.67,0:11:26.19,Default,,0000,0000,0000,,at the earliest phase\Nof discovery chemistry research
Dialogue: 0,0:11:26.21,0:11:27.66,Default,,0000,0000,0000,,as we could be?"
Dialogue: 0,0:11:27.68,0:11:30.02,Default,,0000,0000,0000,,This string of letters and numbers
Dialogue: 0,0:11:30.05,0:11:32.06,Default,,0000,0000,0000,,and symbols and parentheses
Dialogue: 0,0:11:32.08,0:11:33.70,Default,,0000,0000,0000,,that can be texted, I suppose,
Dialogue: 0,0:11:33.73,0:11:35.16,Default,,0000,0000,0000,,or Twittered worldwide,
Dialogue: 0,0:11:36.45,0:11:38.95,Default,,0000,0000,0000,,is the chemical identity\Nof our pro compound.
Dialogue: 0,0:11:38.97,0:11:43.06,Default,,0000,0000,0000,,It's the information that we most need\Nfrom pharmaceutical companies,
Dialogue: 0,0:11:43.08,0:11:47.79,Default,,0000,0000,0000,,the information on how these early\Nprototype drugs might work.
Dialogue: 0,0:11:48.19,0:11:50.31,Default,,0000,0000,0000,,Yet this information is largely a secret.
Dialogue: 0,0:11:50.98,0:11:53.86,Default,,0000,0000,0000,,And so we seek, really, to download
Dialogue: 0,0:11:53.88,0:11:57.00,Default,,0000,0000,0000,,from the amazing successes\Nof the computer-science industry,
Dialogue: 0,0:11:57.03,0:12:01.41,Default,,0000,0000,0000,,two principles -- that of open source\Nand that of crowdsourcing --
Dialogue: 0,0:12:01.43,0:12:07.42,Default,,0000,0000,0000,,to quickly, responsibly accelerate\Nthe delivery of targeted therapeutics
Dialogue: 0,0:12:07.45,0:12:08.96,Default,,0000,0000,0000,,to patients with cancer.
Dialogue: 0,0:12:09.62,0:12:12.74,Default,,0000,0000,0000,,Now, the business model\Ninvolves all of you.
Dialogue: 0,0:12:12.76,0:12:14.74,Default,,0000,0000,0000,,This research is funded by the public.
Dialogue: 0,0:12:15.08,0:12:16.46,Default,,0000,0000,0000,,It's funded by foundations.
Dialogue: 0,0:12:16.49,0:12:18.22,Default,,0000,0000,0000,,And one thing I've learned in Boston
Dialogue: 0,0:12:18.24,0:12:21.32,Default,,0000,0000,0000,,is that you people will do anything\Nfor cancer, and I love that.
Dialogue: 0,0:12:21.34,0:12:24.24,Default,,0000,0000,0000,,You bike across the state,\Nyou walk up and down the river.
Dialogue: 0,0:12:24.26,0:12:25.80,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:12:26.39,0:12:28.72,Default,,0000,0000,0000,,I've never seen, really, anywhere,
Dialogue: 0,0:12:28.74,0:12:31.98,Default,,0000,0000,0000,,this unique support for cancer research.
Dialogue: 0,0:12:32.01,0:12:33.76,Default,,0000,0000,0000,,And so I want to thank you
Dialogue: 0,0:12:33.79,0:12:37.08,Default,,0000,0000,0000,,for your participation, your collaboration
Dialogue: 0,0:12:37.11,0:12:38.27,Default,,0000,0000,0000,,and most of all,
Dialogue: 0,0:12:38.29,0:12:40.23,Default,,0000,0000,0000,,for your confidence in our ideas.
Dialogue: 0,0:12:40.25,0:12:45.75,Default,,0000,0000,0000,,(Applause)