[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.97,0:00:04.26,Default,,0000,0000,0000,,I moved to Boston\N10 years ago from Chicago,
Dialogue: 0,0:00:04.28,0:00:06.88,Default,,0000,0000,0000,,with an interest in cancer\Nand in chemistry.
Dialogue: 0,0:00:07.37,0:00:10.67,Default,,0000,0000,0000,,You might know that chemistry\Nis the science of making molecules
Dialogue: 0,0:00:10.69,0:00:12.01,Default,,0000,0000,0000,,or, to my taste,
Dialogue: 0,0:00:12.03,0:00:13.66,Default,,0000,0000,0000,,new drugs for cancer.
Dialogue: 0,0:00:14.18,0:00:16.98,Default,,0000,0000,0000,,And you might also know that,\Nfor science and medicine,
Dialogue: 0,0:00:17.00,0:00:19.41,Default,,0000,0000,0000,,Boston is a bit of a candy store.
Dialogue: 0,0:00:20.51,0:00:25.13,Default,,0000,0000,0000,,You can't roll a stop sign in Cambridge\Nwithout hitting a graduate student.
Dialogue: 0,0:00:25.15,0:00:27.33,Default,,0000,0000,0000,,The bar is called the Miracle of Science.
Dialogue: 0,0:00:27.73,0:00:30.60,Default,,0000,0000,0000,,The billboards say "Lab Space Available."
Dialogue: 0,0:00:31.40,0:00:33.56,Default,,0000,0000,0000,,And it's fair to say\Nthat in these 10 years,
Dialogue: 0,0:00:33.58,0:00:37.89,Default,,0000,0000,0000,,we've witnessed absolutely the start\Nof a scientific revolution --
Dialogue: 0,0:00:37.91,0:00:39.39,Default,,0000,0000,0000,,that of genome medicine.
Dialogue: 0,0:00:39.78,0:00:42.50,Default,,0000,0000,0000,,We know more about the patients\Nthat enter our clinic now
Dialogue: 0,0:00:42.53,0:00:43.69,Default,,0000,0000,0000,,than ever before.
Dialogue: 0,0:00:43.71,0:00:45.94,Default,,0000,0000,0000,,And we're able, finally,\Nto answer the question
Dialogue: 0,0:00:45.96,0:00:48.32,Default,,0000,0000,0000,,that's been so pressing for so many years:
Dialogue: 0,0:00:48.35,0:00:50.30,Default,,0000,0000,0000,,Why do I have cancer?
Dialogue: 0,0:00:51.42,0:00:53.54,Default,,0000,0000,0000,,This information\Nis also pretty staggering.
Dialogue: 0,0:00:53.96,0:00:57.05,Default,,0000,0000,0000,,You might know that, so far,\Nin just the dawn of this revolution,
Dialogue: 0,0:00:57.07,0:01:00.80,Default,,0000,0000,0000,,we know that there are perhaps\N40,000 unique mutations
Dialogue: 0,0:01:00.82,0:01:03.43,Default,,0000,0000,0000,,affecting more than 10,000 genes,
Dialogue: 0,0:01:03.46,0:01:06.82,Default,,0000,0000,0000,,and that there are 500 of these genes\Nthat are bona-fide drivers,
Dialogue: 0,0:01:06.84,0:01:08.74,Default,,0000,0000,0000,,causes of cancer.
Dialogue: 0,0:01:09.83,0:01:11.03,Default,,0000,0000,0000,,Yet comparatively,
Dialogue: 0,0:01:11.05,0:01:13.82,Default,,0000,0000,0000,,we have about a dozen\Ntargeted medications.
Dialogue: 0,0:01:14.71,0:01:16.97,Default,,0000,0000,0000,,And this inadequacy of cancer medicine
Dialogue: 0,0:01:16.100,0:01:21.11,Default,,0000,0000,0000,,really hit home when my father\Nwas diagnosed with pancreatic cancer.
Dialogue: 0,0:01:22.95,0:01:24.61,Default,,0000,0000,0000,,We didn't fly him to Boston.
Dialogue: 0,0:01:24.64,0:01:26.17,Default,,0000,0000,0000,,We didn't sequence his genome.
Dialogue: 0,0:01:26.55,0:01:29.69,Default,,0000,0000,0000,,It's been known for decades\Nwhat causes this malignancy.
Dialogue: 0,0:01:31.10,0:01:35.15,Default,,0000,0000,0000,,It's three proteins: ras, myc, p53.
Dialogue: 0,0:01:35.68,0:01:38.38,Default,,0000,0000,0000,,This is old information\Nwe've known since about the 80s,
Dialogue: 0,0:01:38.40,0:01:40.32,Default,,0000,0000,0000,,yet there's no medicine I can prescribe
Dialogue: 0,0:01:40.34,0:01:43.91,Default,,0000,0000,0000,,to a patient with this\Nor any of the numerous solid tumors
Dialogue: 0,0:01:43.93,0:01:45.62,Default,,0000,0000,0000,,caused by these three ...
Dialogue: 0,0:01:46.58,0:01:48.89,Default,,0000,0000,0000,,Horsemen of the Apocalypse that is cancer.
Dialogue: 0,0:01:49.28,0:01:51.72,Default,,0000,0000,0000,,There's no ras, no myc, no p53 drug.
Dialogue: 0,0:01:52.10,0:01:54.35,Default,,0000,0000,0000,,And you might fairly ask: Why is that?
Dialogue: 0,0:01:55.05,0:01:57.88,Default,,0000,0000,0000,,And the very unsatisfying\Nyet scientific answer is:
Dialogue: 0,0:01:57.91,0:01:59.06,Default,,0000,0000,0000,,it's too hard.
Dialogue: 0,0:01:59.62,0:02:00.89,Default,,0000,0000,0000,,That for whatever reason,
Dialogue: 0,0:02:00.91,0:02:04.41,Default,,0000,0000,0000,,these three proteins have entered\Na space, in the language of our field,
Dialogue: 0,0:02:04.43,0:02:06.63,Default,,0000,0000,0000,,that's called the undruggable genome --
Dialogue: 0,0:02:06.66,0:02:08.94,Default,,0000,0000,0000,,which is like calling\Na computer unsurfable
Dialogue: 0,0:02:08.97,0:02:10.22,Default,,0000,0000,0000,,or the Moon unwalkable.
Dialogue: 0,0:02:10.25,0:02:12.36,Default,,0000,0000,0000,,It's a horrible term of trade.
Dialogue: 0,0:02:12.38,0:02:13.54,Default,,0000,0000,0000,,But what it means
Dialogue: 0,0:02:13.56,0:02:16.78,Default,,0000,0000,0000,,is that we've failed to identify\Na greasy pocket in these proteins,
Dialogue: 0,0:02:16.81,0:02:19.08,Default,,0000,0000,0000,,into which we, like molecular locksmiths,
Dialogue: 0,0:02:19.10,0:02:24.20,Default,,0000,0000,0000,,can fashion an active, small,\Norganic molecule or drug substance.
Dialogue: 0,0:02:24.77,0:02:27.21,Default,,0000,0000,0000,,Now, as I was training\Nin clinical medicine
Dialogue: 0,0:02:27.23,0:02:30.69,Default,,0000,0000,0000,,and hematology and oncology\Nand stem-cell transplantation,
Dialogue: 0,0:02:30.72,0:02:32.59,Default,,0000,0000,0000,,what we had instead,
Dialogue: 0,0:02:32.61,0:02:36.13,Default,,0000,0000,0000,,cascading through the regulatory\Nnetwork at the FDA,
Dialogue: 0,0:02:36.15,0:02:37.58,Default,,0000,0000,0000,,were these substances:
Dialogue: 0,0:02:37.61,0:02:38.92,Default,,0000,0000,0000,,arsenic,
Dialogue: 0,0:02:38.94,0:02:40.11,Default,,0000,0000,0000,,thalidomide,
Dialogue: 0,0:02:40.13,0:02:43.49,Default,,0000,0000,0000,,and this chemical derivative\Nof nitrogen mustard gas.
Dialogue: 0,0:02:43.51,0:02:46.12,Default,,0000,0000,0000,,And this is the 21st century.
Dialogue: 0,0:02:46.14,0:02:47.39,Default,,0000,0000,0000,,And so, I guess you'd say,
Dialogue: 0,0:02:47.42,0:02:50.55,Default,,0000,0000,0000,,dissatisfied with the performance\Nand quality of these medicines,
Dialogue: 0,0:02:50.58,0:02:52.85,Default,,0000,0000,0000,,I went back to school, in chemistry,
Dialogue: 0,0:02:54.05,0:02:58.71,Default,,0000,0000,0000,,with the idea that perhaps by learning\Nthe trade of discovery chemistry
Dialogue: 0,0:02:58.73,0:03:01.60,Default,,0000,0000,0000,,and approaching it in the context\Nof this brave new world
Dialogue: 0,0:03:01.63,0:03:03.84,Default,,0000,0000,0000,,of the open source,
Dialogue: 0,0:03:03.86,0:03:05.29,Default,,0000,0000,0000,,the crowd source,
Dialogue: 0,0:03:05.32,0:03:08.62,Default,,0000,0000,0000,,the collaborative network\Nthat we have access to within academia,
Dialogue: 0,0:03:08.65,0:03:12.92,Default,,0000,0000,0000,,that we might more quickly bring\Npowerful and targeted therapies
Dialogue: 0,0:03:12.95,0:03:14.31,Default,,0000,0000,0000,,to our patients.
Dialogue: 0,0:03:14.69,0:03:17.79,Default,,0000,0000,0000,,And so, please consider\Nthis a work in progress,
Dialogue: 0,0:03:17.82,0:03:19.83,Default,,0000,0000,0000,,but I'd like to tell you today a story
Dialogue: 0,0:03:19.86,0:03:23.06,Default,,0000,0000,0000,,about a very rare cancer\Ncalled midline carcinoma,
Dialogue: 0,0:03:23.86,0:03:28.07,Default,,0000,0000,0000,,about the undruggable protein target\Nthat causes this cancer,
Dialogue: 0,0:03:28.10,0:03:29.62,Default,,0000,0000,0000,,called BRD4,
Dialogue: 0,0:03:29.65,0:03:33.49,Default,,0000,0000,0000,,and about a molecule developed at my lab\Nat Dana-Farber Cancer Institute,
Dialogue: 0,0:03:33.52,0:03:34.67,Default,,0000,0000,0000,,called JQ1,
Dialogue: 0,0:03:34.69,0:03:36.92,Default,,0000,0000,0000,,which we affectionately named for Jun Qi,
Dialogue: 0,0:03:36.94,0:03:38.98,Default,,0000,0000,0000,,the chemist that made this molecule.
Dialogue: 0,0:03:39.71,0:03:42.40,Default,,0000,0000,0000,,Now, BRD4 is an interesting protein.
Dialogue: 0,0:03:42.43,0:03:46.11,Default,,0000,0000,0000,,You might ask: with all the things\Ncancer's trying to do to kill our patient,
Dialogue: 0,0:03:46.13,0:03:47.72,Default,,0000,0000,0000,,how does it remember it's cancer?
Dialogue: 0,0:03:47.75,0:03:49.18,Default,,0000,0000,0000,,When it winds up its genome,
Dialogue: 0,0:03:49.20,0:03:51.57,Default,,0000,0000,0000,,divides into two cells and unwinds again,
Dialogue: 0,0:03:51.60,0:03:53.83,Default,,0000,0000,0000,,why does it not turn\Ninto an eye, into a liver,
Dialogue: 0,0:03:53.86,0:03:56.24,Default,,0000,0000,0000,,as it has all the genes\Nnecessary to do this?
Dialogue: 0,0:03:56.26,0:03:57.82,Default,,0000,0000,0000,,It remembers that it's cancer.
Dialogue: 0,0:03:58.69,0:04:01.78,Default,,0000,0000,0000,,And the reason is that cancer,\Nlike every cell in the body,
Dialogue: 0,0:04:01.80,0:04:03.78,Default,,0000,0000,0000,,places little molecular bookmarks,
Dialogue: 0,0:04:03.80,0:04:05.18,Default,,0000,0000,0000,,little Post-it notes,
Dialogue: 0,0:04:05.20,0:04:08.18,Default,,0000,0000,0000,,that remind the cell, "I'm cancer;\NI should keep growing."
Dialogue: 0,0:04:08.80,0:04:12.81,Default,,0000,0000,0000,,And those Post-it notes involve this\Nand other proteins of its class --
Dialogue: 0,0:04:12.84,0:04:14.15,Default,,0000,0000,0000,,so-called bromodomains.
Dialogue: 0,0:04:14.73,0:04:17.40,Default,,0000,0000,0000,,So we developed an idea, a rationale,
Dialogue: 0,0:04:17.42,0:04:19.57,Default,,0000,0000,0000,,that perhaps if we made a molecule
Dialogue: 0,0:04:19.60,0:04:21.89,Default,,0000,0000,0000,,that prevented\Nthe Post-it note from sticking
Dialogue: 0,0:04:21.91,0:04:23.57,Default,,0000,0000,0000,,by entering into the little pocket
Dialogue: 0,0:04:23.60,0:04:25.45,Default,,0000,0000,0000,,at the base of this spinning protein,
Dialogue: 0,0:04:25.48,0:04:27.53,Default,,0000,0000,0000,,then maybe we could convince cancer cells,
Dialogue: 0,0:04:27.56,0:04:30.36,Default,,0000,0000,0000,,certainly those addicted\Nto this BRD4 protein,
Dialogue: 0,0:04:30.38,0:04:31.70,Default,,0000,0000,0000,,that they're not cancer.
Dialogue: 0,0:04:32.42,0:04:34.64,Default,,0000,0000,0000,,And so we started to work on this problem.
Dialogue: 0,0:04:34.66,0:04:36.97,Default,,0000,0000,0000,,We developed libraries of compounds
Dialogue: 0,0:04:36.99,0:04:39.78,Default,,0000,0000,0000,,and eventually arrived\Nat this and similar substances
Dialogue: 0,0:04:39.80,0:04:40.98,Default,,0000,0000,0000,,called JQ1.
Dialogue: 0,0:04:41.58,0:04:43.14,Default,,0000,0000,0000,,Now, not being a drug company,
Dialogue: 0,0:04:43.16,0:04:46.26,Default,,0000,0000,0000,,we could do certain things,\Nwe had certain flexibilities,
Dialogue: 0,0:04:46.28,0:04:49.12,Default,,0000,0000,0000,,that I respect that a pharmaceutical\Nindustry doesn't have.
Dialogue: 0,0:04:49.14,0:04:51.39,Default,,0000,0000,0000,,We just started mailing it to our friends.
Dialogue: 0,0:04:51.88,0:04:53.04,Default,,0000,0000,0000,,I have a small lab.
Dialogue: 0,0:04:53.06,0:04:56.46,Default,,0000,0000,0000,,We thought we'd just send it to people\Nand see how the molecule behaves.
Dialogue: 0,0:04:56.49,0:04:57.94,Default,,0000,0000,0000,,We sent it to Oxford, England,
Dialogue: 0,0:04:57.96,0:05:01.18,Default,,0000,0000,0000,,where a group of talented\Ncrystallographers provided this picture,
Dialogue: 0,0:05:01.21,0:05:04.31,Default,,0000,0000,0000,,which helped us understand exactly\Nhow this molecule is so potent
Dialogue: 0,0:05:04.33,0:05:05.50,Default,,0000,0000,0000,,for this protein target.
Dialogue: 0,0:05:05.52,0:05:08.46,Default,,0000,0000,0000,,It's what we call a perfect fit\Nof shape complementarity,
Dialogue: 0,0:05:08.48,0:05:09.63,Default,,0000,0000,0000,,or hand in glove.
Dialogue: 0,0:05:10.33,0:05:11.95,Default,,0000,0000,0000,,Now, this is a very rare cancer,
Dialogue: 0,0:05:11.97,0:05:13.78,Default,,0000,0000,0000,,this BRD4-addicted cancer.
Dialogue: 0,0:05:14.20,0:05:16.43,Default,,0000,0000,0000,,And so we worked with samples of material
Dialogue: 0,0:05:16.46,0:05:20.03,Default,,0000,0000,0000,,that were collected by young pathologists\Nat Brigham and Women's Hospital.
Dialogue: 0,0:05:20.05,0:05:22.43,Default,,0000,0000,0000,,And as we treated these cells\Nwith this molecule,
Dialogue: 0,0:05:22.45,0:05:24.49,Default,,0000,0000,0000,,we observed something really striking.
Dialogue: 0,0:05:24.80,0:05:26.01,Default,,0000,0000,0000,,The cancer cells --
Dialogue: 0,0:05:26.03,0:05:28.10,Default,,0000,0000,0000,,small, round and rapidly dividing,
Dialogue: 0,0:05:28.12,0:05:30.47,Default,,0000,0000,0000,,grew these arms and extensions.
Dialogue: 0,0:05:30.50,0:05:31.86,Default,,0000,0000,0000,,They were changing shape.
Dialogue: 0,0:05:32.32,0:05:33.65,Default,,0000,0000,0000,,In effect,
Dialogue: 0,0:05:33.67,0:05:36.98,Default,,0000,0000,0000,,the cancer cell\Nwas forgetting it was cancer
Dialogue: 0,0:05:37.00,0:05:38.51,Default,,0000,0000,0000,,and becoming a normal cell.
Dialogue: 0,0:05:40.08,0:05:41.43,Default,,0000,0000,0000,,This got us very excited.
Dialogue: 0,0:05:42.84,0:05:45.43,Default,,0000,0000,0000,,The next step would be to put\Nthis molecule into mice.
Dialogue: 0,0:05:45.45,0:05:48.85,Default,,0000,0000,0000,,The only problem was there's no\Nmouse model of this rare cancer.
Dialogue: 0,0:05:48.87,0:05:51.60,Default,,0000,0000,0000,,And so at the time\Nwe were doing this research,
Dialogue: 0,0:05:51.62,0:05:55.19,Default,,0000,0000,0000,,I was caring for a 29-year-old\Nfirefighter from Connecticut
Dialogue: 0,0:05:55.22,0:05:57.10,Default,,0000,0000,0000,,who was very much at the end of life
Dialogue: 0,0:05:57.12,0:05:58.98,Default,,0000,0000,0000,,with this incurable cancer.
Dialogue: 0,0:05:59.62,0:06:03.07,Default,,0000,0000,0000,,This BRD4-addicted cancer\Nwas growing throughout his left lung.
Dialogue: 0,0:06:03.10,0:06:06.26,Default,,0000,0000,0000,,And he had a chest tube in\Nthat was draining little bits of debris.
Dialogue: 0,0:06:06.28,0:06:09.24,Default,,0000,0000,0000,,And every nursing shift,\Nwe would throw this material out.
Dialogue: 0,0:06:09.27,0:06:11.04,Default,,0000,0000,0000,,And so we approached this patient
Dialogue: 0,0:06:11.06,0:06:13.07,Default,,0000,0000,0000,,and asked if he would collaborate with us.
Dialogue: 0,0:06:13.72,0:06:17.41,Default,,0000,0000,0000,,Could we take this precious\Nand rare cancerous material
Dialogue: 0,0:06:17.44,0:06:19.04,Default,,0000,0000,0000,,from this chest tube
Dialogue: 0,0:06:19.06,0:06:21.28,Default,,0000,0000,0000,,and drive it across town\Nand put it into mice
Dialogue: 0,0:06:21.30,0:06:24.94,Default,,0000,0000,0000,,and try to do a clinical trial\Nat a stage that with a prototype drug,
Dialogue: 0,0:06:24.97,0:06:26.99,Default,,0000,0000,0000,,well, that would be, of course, impossible
Dialogue: 0,0:06:27.02,0:06:28.85,Default,,0000,0000,0000,,and, rightly, illegal to do in humans.
Dialogue: 0,0:06:28.87,0:06:30.13,Default,,0000,0000,0000,,And he obliged us.
Dialogue: 0,0:06:31.01,0:06:33.20,Default,,0000,0000,0000,,At the Lurie Family Center\Nfor Animal Imaging,
Dialogue: 0,0:06:33.22,0:06:36.84,Default,,0000,0000,0000,,our colleague, Andrew Kung,\Ngrew this cancer successfully in mice
Dialogue: 0,0:06:36.86,0:06:38.55,Default,,0000,0000,0000,,without ever touching plastic.
Dialogue: 0,0:06:38.58,0:06:41.99,Default,,0000,0000,0000,,And you can see this PET scan\Nof a mouse -- what we call a pet PET.
Dialogue: 0,0:06:42.02,0:06:43.57,Default,,0000,0000,0000,,The cancer is growing
Dialogue: 0,0:06:43.60,0:06:46.50,Default,,0000,0000,0000,,as this red, huge mass\Nin the hind limb of this animal.
Dialogue: 0,0:06:46.92,0:06:49.14,Default,,0000,0000,0000,,And as we treat it with our compound,
Dialogue: 0,0:06:49.17,0:06:50.78,Default,,0000,0000,0000,,this addiction to sugar,
Dialogue: 0,0:06:50.80,0:06:52.39,Default,,0000,0000,0000,,this rapid growth, faded.
Dialogue: 0,0:06:52.42,0:06:54.46,Default,,0000,0000,0000,,And on the animal on the right,
Dialogue: 0,0:06:54.48,0:06:56.49,Default,,0000,0000,0000,,you see that the cancer was responding.
Dialogue: 0,0:06:57.57,0:06:59.78,Default,,0000,0000,0000,,We've completed, now, clinical trials
Dialogue: 0,0:06:59.80,0:07:01.78,Default,,0000,0000,0000,,in four mouse models of this disease.
Dialogue: 0,0:07:01.80,0:07:03.65,Default,,0000,0000,0000,,And every time, we see the same thing.
Dialogue: 0,0:07:03.67,0:07:06.38,Default,,0000,0000,0000,,The mice with this cancer\Nthat get the drug live,
Dialogue: 0,0:07:06.40,0:07:08.70,Default,,0000,0000,0000,,and the ones that don't rapidly perish.
Dialogue: 0,0:07:10.80,0:07:12.23,Default,,0000,0000,0000,,So we started to wonder,
Dialogue: 0,0:07:12.25,0:07:14.36,Default,,0000,0000,0000,,what would a drug company\Ndo at this point?
Dialogue: 0,0:07:14.38,0:07:16.43,Default,,0000,0000,0000,,Well, they probably\Nwould keep this a secret
Dialogue: 0,0:07:16.45,0:07:18.34,Default,,0000,0000,0000,,until they turn the prototype drug
Dialogue: 0,0:07:18.36,0:07:20.51,Default,,0000,0000,0000,,into an active pharmaceutical substance.
Dialogue: 0,0:07:21.06,0:07:22.50,Default,,0000,0000,0000,,So we did just the opposite.
Dialogue: 0,0:07:22.88,0:07:25.72,Default,,0000,0000,0000,,We published a paper\Nthat described this finding
Dialogue: 0,0:07:25.74,0:07:27.72,Default,,0000,0000,0000,,at the earliest prototype stage.
Dialogue: 0,0:07:28.51,0:07:31.42,Default,,0000,0000,0000,,We gave the world the chemical\Nidentity of this molecule,
Dialogue: 0,0:07:31.44,0:07:33.34,Default,,0000,0000,0000,,typically a secret in our discipline.
Dialogue: 0,0:07:33.37,0:07:35.34,Default,,0000,0000,0000,,We told people exactly how to make it.
Dialogue: 0,0:07:36.04,0:07:37.71,Default,,0000,0000,0000,,We gave them our email address,
Dialogue: 0,0:07:37.73,0:07:39.38,Default,,0000,0000,0000,,suggesting that if they write us,
Dialogue: 0,0:07:39.41,0:07:41.01,Default,,0000,0000,0000,,we'll send them a free molecule.
Dialogue: 0,0:07:41.03,0:07:42.12,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:07:42.14,0:07:45.04,Default,,0000,0000,0000,,We basically tried to create\Nthe most competitive environment
Dialogue: 0,0:07:45.06,0:07:46.22,Default,,0000,0000,0000,,for our lab as possible.
Dialogue: 0,0:07:46.25,0:07:48.19,Default,,0000,0000,0000,,And this was, unfortunately, successful.
Dialogue: 0,0:07:48.22,0:07:49.24,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:07:49.26,0:07:51.27,Default,,0000,0000,0000,,Because now, we've shared this molecule,
Dialogue: 0,0:07:51.29,0:07:53.70,Default,,0000,0000,0000,,just since December of last year,
Dialogue: 0,0:07:53.72,0:07:55.97,Default,,0000,0000,0000,,with 40 laboratories in the United States
Dialogue: 0,0:07:55.100,0:07:57.78,Default,,0000,0000,0000,,and 30 more in Europe --
Dialogue: 0,0:07:57.80,0:07:59.65,Default,,0000,0000,0000,,many of them pharmaceutical companies,
Dialogue: 0,0:07:59.67,0:08:01.27,Default,,0000,0000,0000,,seeking now to enter this space,
Dialogue: 0,0:08:01.29,0:08:04.34,Default,,0000,0000,0000,,to target this rare cancer\Nthat, thankfully right now,
Dialogue: 0,0:08:05.20,0:08:07.81,Default,,0000,0000,0000,,is quite desirable\Nto study in that industry.
Dialogue: 0,0:08:10.06,0:08:13.13,Default,,0000,0000,0000,,But the science that's coming back\Nfrom all of these laboratories
Dialogue: 0,0:08:13.16,0:08:14.99,Default,,0000,0000,0000,,about the use of this molecule
Dialogue: 0,0:08:15.01,0:08:18.19,Default,,0000,0000,0000,,has provided us insights\Nwe might not have had on our own.
Dialogue: 0,0:08:18.21,0:08:20.19,Default,,0000,0000,0000,,Leukemia cells treated with this compound
Dialogue: 0,0:08:20.21,0:08:22.63,Default,,0000,0000,0000,,turn into normal white blood cells.
Dialogue: 0,0:08:23.28,0:08:25.06,Default,,0000,0000,0000,,Mice with multiple myeloma,
Dialogue: 0,0:08:25.08,0:08:28.12,Default,,0000,0000,0000,,an incurable malignancy\Nof the bone marrow,
Dialogue: 0,0:08:28.14,0:08:30.12,Default,,0000,0000,0000,,respond dramatically
Dialogue: 0,0:08:30.14,0:08:31.86,Default,,0000,0000,0000,,to the treatment with this drug.
Dialogue: 0,0:08:32.32,0:08:34.29,Default,,0000,0000,0000,,You might know that fat has memory.
Dialogue: 0,0:08:35.36,0:08:37.34,Default,,0000,0000,0000,,I'll nicely demonstrate that for you.
Dialogue: 0,0:08:37.36,0:08:38.40,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:08:38.42,0:08:39.97,Default,,0000,0000,0000,,In fact, this molecule
Dialogue: 0,0:08:39.100,0:08:43.40,Default,,0000,0000,0000,,prevents this adipocyte,\Nthis fat stem cell,
Dialogue: 0,0:08:43.42,0:08:46.29,Default,,0000,0000,0000,,from remembering how to make fat,
Dialogue: 0,0:08:46.31,0:08:48.68,Default,,0000,0000,0000,,such that mice on a high-fat diet,
Dialogue: 0,0:08:48.70,0:08:50.82,Default,,0000,0000,0000,,like the folks\Nin my hometown of Chicago --
Dialogue: 0,0:08:50.84,0:08:51.85,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:08:51.87,0:08:53.88,Default,,0000,0000,0000,,fail to develop fatty liver,
Dialogue: 0,0:08:53.91,0:08:55.73,Default,,0000,0000,0000,,which is a major medical problem.
Dialogue: 0,0:08:56.92,0:08:58.49,Default,,0000,0000,0000,,What this research taught us --
Dialogue: 0,0:08:58.52,0:09:00.78,Default,,0000,0000,0000,,not just my lab, but our institute,
Dialogue: 0,0:09:00.80,0:09:02.87,Default,,0000,0000,0000,,and Harvard Medical School\Nmore generally --
Dialogue: 0,0:09:02.90,0:09:05.16,Default,,0000,0000,0000,,is that we have unique\Nresources in academia
Dialogue: 0,0:09:05.18,0:09:06.52,Default,,0000,0000,0000,,for drug discovery;
Dialogue: 0,0:09:06.54,0:09:09.72,Default,,0000,0000,0000,,that our center, which has tested\Nperhaps more cancer molecules
Dialogue: 0,0:09:09.75,0:09:10.90,Default,,0000,0000,0000,,in a scientific way
Dialogue: 0,0:09:10.93,0:09:12.08,Default,,0000,0000,0000,,than any other,
Dialogue: 0,0:09:12.10,0:09:13.58,Default,,0000,0000,0000,,never made one of its own.
Dialogue: 0,0:09:14.54,0:09:16.71,Default,,0000,0000,0000,,For all the reasons you see listed here,
Dialogue: 0,0:09:16.74,0:09:19.48,Default,,0000,0000,0000,,we think there's a great\Nopportunity for academic centers
Dialogue: 0,0:09:19.50,0:09:23.32,Default,,0000,0000,0000,,to participate in this earliest,\Nconceptually tricky
Dialogue: 0,0:09:23.35,0:09:25.28,Default,,0000,0000,0000,,and creative discipline
Dialogue: 0,0:09:25.30,0:09:27.08,Default,,0000,0000,0000,,of prototype drug discovery.
Dialogue: 0,0:09:29.87,0:09:31.02,Default,,0000,0000,0000,,So what next?
Dialogue: 0,0:09:31.35,0:09:33.73,Default,,0000,0000,0000,,We have this molecule,\Nbut it's not a pill yet.
Dialogue: 0,0:09:33.75,0:09:36.35,Default,,0000,0000,0000,,It's not orally bioavailable.
Dialogue: 0,0:09:36.37,0:09:39.57,Default,,0000,0000,0000,,We need to fix it so we can\Ndeliver it to our patients.
Dialogue: 0,0:09:39.59,0:09:41.17,Default,,0000,0000,0000,,And everyone in the lab,
Dialogue: 0,0:09:41.20,0:09:43.100,Default,,0000,0000,0000,,especially following the interaction\Nwith these patients,
Dialogue: 0,0:09:44.02,0:09:46.35,Default,,0000,0000,0000,,feels quite compelled\Nto deliver a drug substance
Dialogue: 0,0:09:46.37,0:09:47.57,Default,,0000,0000,0000,,based on this molecule.
Dialogue: 0,0:09:47.59,0:09:49.00,Default,,0000,0000,0000,,It's here where I'd say
Dialogue: 0,0:09:49.03,0:09:51.24,Default,,0000,0000,0000,,that we could use your help\Nand your insights,
Dialogue: 0,0:09:51.27,0:09:53.13,Default,,0000,0000,0000,,your collaborative participation.
Dialogue: 0,0:09:53.48,0:09:57.16,Default,,0000,0000,0000,,Unlike a drug company,\Nwe don't have a pipeline
Dialogue: 0,0:09:57.19,0:09:59.19,Default,,0000,0000,0000,,that we can deposit these molecules into.
Dialogue: 0,0:09:59.22,0:10:01.61,Default,,0000,0000,0000,,We don't have a team\Nof salespeople and marketeers
Dialogue: 0,0:10:01.64,0:10:04.35,Default,,0000,0000,0000,,to tell us how to position\Nthis drug against the other.
Dialogue: 0,0:10:04.37,0:10:07.04,Default,,0000,0000,0000,,What we do have is the flexibility\Nof an academic center
Dialogue: 0,0:10:07.06,0:10:09.42,Default,,0000,0000,0000,,to work with competent, motivated,
Dialogue: 0,0:10:09.44,0:10:12.35,Default,,0000,0000,0000,,enthusiastic, hopefully well-funded people
Dialogue: 0,0:10:12.37,0:10:14.66,Default,,0000,0000,0000,,to carry these molecules\Nforward into the clinic
Dialogue: 0,0:10:14.69,0:10:18.38,Default,,0000,0000,0000,,while preserving our ability\Nto share the prototype drug worldwide.
Dialogue: 0,0:10:19.47,0:10:22.12,Default,,0000,0000,0000,,This molecule will soon leave our benches
Dialogue: 0,0:10:22.14,0:10:25.19,Default,,0000,0000,0000,,and go into a small start-up company\Ncalled Tensha Therapeutics.
Dialogue: 0,0:10:25.21,0:10:28.15,Default,,0000,0000,0000,,And, really, this is the fourth\Nof these molecules
Dialogue: 0,0:10:28.17,0:10:30.42,Default,,0000,0000,0000,,to kind of "graduate"\Nfrom our little pipeline
Dialogue: 0,0:10:30.44,0:10:31.90,Default,,0000,0000,0000,,of drug discovery,
Dialogue: 0,0:10:31.92,0:10:36.28,Default,,0000,0000,0000,,two of which -- a topical drug\Nfor lymphoma of the skin
Dialogue: 0,0:10:37.20,0:10:40.31,Default,,0000,0000,0000,,and an oral substance for the treatment\Nof multiple myeloma --
Dialogue: 0,0:10:40.33,0:10:43.57,Default,,0000,0000,0000,,will actually come to the bedside\Nfor the first clinical trial
Dialogue: 0,0:10:43.59,0:10:47.12,Default,,0000,0000,0000,,in July of this year -- for us,\Na major and exciting milestone.
Dialogue: 0,0:10:48.65,0:10:50.67,Default,,0000,0000,0000,,I want to leave you with just two ideas.
Dialogue: 0,0:10:50.70,0:10:55.03,Default,,0000,0000,0000,,The first is: if anything is unique\Nabout this research,
Dialogue: 0,0:10:55.05,0:10:57.41,Default,,0000,0000,0000,,it's less the science than the strategy.
Dialogue: 0,0:10:57.44,0:10:59.86,Default,,0000,0000,0000,,This, for us, was a social experiment --
Dialogue: 0,0:10:59.88,0:11:05.15,Default,,0000,0000,0000,,an experiment in "What would happen\Nif we were as open and honest
Dialogue: 0,0:11:05.17,0:11:07.69,Default,,0000,0000,0000,,at the earliest phase\Nof discovery chemistry research
Dialogue: 0,0:11:07.71,0:11:09.16,Default,,0000,0000,0000,,as we could be?"
Dialogue: 0,0:11:09.18,0:11:11.52,Default,,0000,0000,0000,,This string of letters and numbers
Dialogue: 0,0:11:11.55,0:11:13.56,Default,,0000,0000,0000,,and symbols and parentheses
Dialogue: 0,0:11:13.58,0:11:15.20,Default,,0000,0000,0000,,that can be texted, I suppose,
Dialogue: 0,0:11:15.23,0:11:16.66,Default,,0000,0000,0000,,or Twittered worldwide,
Dialogue: 0,0:11:17.95,0:11:20.45,Default,,0000,0000,0000,,is the chemical identity\Nof our pro compound.
Dialogue: 0,0:11:20.47,0:11:24.56,Default,,0000,0000,0000,,It's the information that we most need\Nfrom pharmaceutical companies,
Dialogue: 0,0:11:24.58,0:11:29.29,Default,,0000,0000,0000,,the information on how these early\Nprototype drugs might work.
Dialogue: 0,0:11:29.69,0:11:31.81,Default,,0000,0000,0000,,Yet this information is largely a secret.
Dialogue: 0,0:11:32.48,0:11:35.36,Default,,0000,0000,0000,,And so we seek, really, to download
Dialogue: 0,0:11:35.38,0:11:38.50,Default,,0000,0000,0000,,from the amazing successes\Nof the computer-science industry,
Dialogue: 0,0:11:38.53,0:11:42.91,Default,,0000,0000,0000,,two principles -- that of open source\Nand that of crowdsourcing --
Dialogue: 0,0:11:42.93,0:11:48.92,Default,,0000,0000,0000,,to quickly, responsibly accelerate\Nthe delivery of targeted therapeutics
Dialogue: 0,0:11:48.95,0:11:50.46,Default,,0000,0000,0000,,to patients with cancer.
Dialogue: 0,0:11:51.12,0:11:54.24,Default,,0000,0000,0000,,Now, the business model\Ninvolves all of you.
Dialogue: 0,0:11:54.26,0:11:56.24,Default,,0000,0000,0000,,This research is funded by the public.
Dialogue: 0,0:11:56.58,0:11:57.96,Default,,0000,0000,0000,,It's funded by foundations.
Dialogue: 0,0:11:57.99,0:11:59.72,Default,,0000,0000,0000,,And one thing I've learned in Boston
Dialogue: 0,0:11:59.74,0:12:02.82,Default,,0000,0000,0000,,is that you people will do anything\Nfor cancer, and I love that.
Dialogue: 0,0:12:02.84,0:12:05.74,Default,,0000,0000,0000,,You bike across the state,\Nyou walk up and down the river.
Dialogue: 0,0:12:05.76,0:12:07.30,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:12:07.89,0:12:10.22,Default,,0000,0000,0000,,I've never seen, really, anywhere,
Dialogue: 0,0:12:10.24,0:12:13.48,Default,,0000,0000,0000,,this unique support for cancer research.
Dialogue: 0,0:12:13.51,0:12:15.26,Default,,0000,0000,0000,,And so I want to thank you
Dialogue: 0,0:12:15.29,0:12:18.58,Default,,0000,0000,0000,,for your participation, your collaboration
Dialogue: 0,0:12:18.61,0:12:19.77,Default,,0000,0000,0000,,and most of all,
Dialogue: 0,0:12:19.79,0:12:21.73,Default,,0000,0000,0000,,for your confidence in our ideas.
Dialogue: 0,0:12:21.75,0:12:27.25,Default,,0000,0000,0000,,(Applause)