[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.76,0:00:02.10,Default,,0000,0000,0000,,All life,
Dialogue: 0,0:00:02.12,0:00:03.86,Default,,0000,0000,0000,,every living thing ever,
Dialogue: 0,0:00:03.88,0:00:06.82,Default,,0000,0000,0000,,has been built according\Nto the information in DNA.
Dialogue: 0,0:00:06.84,0:00:08.22,Default,,0000,0000,0000,,What does that mean?
Dialogue: 0,0:00:08.24,0:00:10.74,Default,,0000,0000,0000,,Well, it means that just\Nas the English language
Dialogue: 0,0:00:10.76,0:00:13.98,Default,,0000,0000,0000,,is made up of alphabetic letters\Nthat, when combined into words,
Dialogue: 0,0:00:14.00,0:00:16.82,Default,,0000,0000,0000,,allow me to tell you the story\NI'm going to tell you today,
Dialogue: 0,0:00:16.84,0:00:20.94,Default,,0000,0000,0000,,DNA is made up of genetic letters\Nthat, when combined into genes,
Dialogue: 0,0:00:20.96,0:00:22.70,Default,,0000,0000,0000,,allow cells to produce proteins,
Dialogue: 0,0:00:22.72,0:00:25.78,Default,,0000,0000,0000,,strings of amino acids\Nthat fold up into complex structures
Dialogue: 0,0:00:25.80,0:00:28.82,Default,,0000,0000,0000,,that perform the functions\Nthat allow a cell to do what it does,
Dialogue: 0,0:00:28.84,0:00:30.58,Default,,0000,0000,0000,,to tell its stories.
Dialogue: 0,0:00:30.60,0:00:34.54,Default,,0000,0000,0000,,The English alphabet has 26 letters,\Nand the genetic alphabet has four.
Dialogue: 0,0:00:34.56,0:00:36.94,Default,,0000,0000,0000,,They're pretty famous.\NMaybe you've heard of them.
Dialogue: 0,0:00:36.96,0:00:39.28,Default,,0000,0000,0000,,They are often just\Nreferred to as G, C, A and T.
Dialogue: 0,0:00:40.52,0:00:43.94,Default,,0000,0000,0000,,But it's remarkable\Nthat all the diversity of life
Dialogue: 0,0:00:43.96,0:00:46.04,Default,,0000,0000,0000,,is the result of four genetic letters.
Dialogue: 0,0:00:47.24,0:00:51.26,Default,,0000,0000,0000,,Imagine what it would be like\Nif the English alphabet had four letters.
Dialogue: 0,0:00:51.28,0:00:53.56,Default,,0000,0000,0000,,What sort of stories\Nwould you be able to tell?
Dialogue: 0,0:00:55.28,0:00:57.44,Default,,0000,0000,0000,,What if the genetic alphabet\Nhad more letters?
Dialogue: 0,0:00:59.44,0:01:02.42,Default,,0000,0000,0000,,Would life with more letters\Nbe able to tell different stories,
Dialogue: 0,0:01:02.44,0:01:04.44,Default,,0000,0000,0000,,maybe even more interesting ones?
Dialogue: 0,0:01:06.48,0:01:10.30,Default,,0000,0000,0000,,In 1999, my lab at the Scripps\NResearch Institute in La Jolla, California
Dialogue: 0,0:01:10.32,0:01:14.02,Default,,0000,0000,0000,,started working on this question\Nwith the goal of creating living organisms
Dialogue: 0,0:01:14.04,0:01:17.06,Default,,0000,0000,0000,,with DNA made up\Nof a six-letter genetic alphabet,
Dialogue: 0,0:01:17.08,0:01:21.56,Default,,0000,0000,0000,,the four natural letters\Nplus two additional new man-made letters.
Dialogue: 0,0:01:23.12,0:01:24.38,Default,,0000,0000,0000,,Such an organism would be
Dialogue: 0,0:01:24.40,0:01:27.26,Default,,0000,0000,0000,,the first radically altered\Nform of life ever created.
Dialogue: 0,0:01:27.28,0:01:29.22,Default,,0000,0000,0000,,It would be a semisynthetic form of life
Dialogue: 0,0:01:29.24,0:01:33.12,Default,,0000,0000,0000,,that stores more information\Nthan life ever has before.
Dialogue: 0,0:01:34.12,0:01:35.98,Default,,0000,0000,0000,,It would be able to make new proteins,
Dialogue: 0,0:01:36.00,0:01:38.74,Default,,0000,0000,0000,,proteins built from more\Nthan the 20 normal amino acids
Dialogue: 0,0:01:38.76,0:01:40.68,Default,,0000,0000,0000,,that are usually used to build proteins.
Dialogue: 0,0:01:41.56,0:01:43.64,Default,,0000,0000,0000,,What sort of stories could that life tell?
Dialogue: 0,0:01:45.40,0:01:48.22,Default,,0000,0000,0000,,With the power of synthetic chemistry\Nand molecular biology
Dialogue: 0,0:01:48.24,0:01:49.82,Default,,0000,0000,0000,,and just under 20 years of work,
Dialogue: 0,0:01:49.84,0:01:52.38,Default,,0000,0000,0000,,we created bacteria with six-letter DNA.
Dialogue: 0,0:01:52.40,0:01:53.83,Default,,0000,0000,0000,,Let me tell you how we did it.
Dialogue: 0,0:01:54.64,0:01:57.18,Default,,0000,0000,0000,,All you have to remember\Nfrom your high school biology
Dialogue: 0,0:01:57.20,0:02:00.70,Default,,0000,0000,0000,,is that the four natural letters\Npair together to form two base pairs.
Dialogue: 0,0:02:00.72,0:02:02.98,Default,,0000,0000,0000,,G pairs with C and A pairs with T,
Dialogue: 0,0:02:03.00,0:02:04.82,Default,,0000,0000,0000,,so to create our new letters,
Dialogue: 0,0:02:04.84,0:02:08.38,Default,,0000,0000,0000,,we synthesized hundreds of new candidates,\Nnew candidate letters,
Dialogue: 0,0:02:08.40,0:02:11.45,Default,,0000,0000,0000,,and examined their abilities\Nto selectively pair with each other.
Dialogue: 0,0:02:11.47,0:02:13.18,Default,,0000,0000,0000,,And after about 15 years of work,
Dialogue: 0,0:02:13.20,0:02:15.78,Default,,0000,0000,0000,,we found two that paired\Ntogether really well,
Dialogue: 0,0:02:15.80,0:02:17.50,Default,,0000,0000,0000,,at least in a test tube.
Dialogue: 0,0:02:17.52,0:02:19.22,Default,,0000,0000,0000,,They have complicated names,
Dialogue: 0,0:02:19.24,0:02:20.86,Default,,0000,0000,0000,,but let's just call them X and Y.
Dialogue: 0,0:02:21.96,0:02:25.38,Default,,0000,0000,0000,,The next thing we needed to do\Nwas find a way to get X and Y into cells,
Dialogue: 0,0:02:25.40,0:02:28.94,Default,,0000,0000,0000,,and eventually we found that a protein\Nthat does something similar in algae
Dialogue: 0,0:02:28.96,0:02:30.34,Default,,0000,0000,0000,,worked in our bacteria.
Dialogue: 0,0:02:30.36,0:02:34.86,Default,,0000,0000,0000,,So the final thing that we needed to do\Nwas to show that with X and Y provided,
Dialogue: 0,0:02:34.88,0:02:38.40,Default,,0000,0000,0000,,cells could grow and divide\Nand hold on to X and Y in their DNA.
Dialogue: 0,0:02:39.88,0:02:42.98,Default,,0000,0000,0000,,Everything we had done up to then\Ntook longer than I had hoped --
Dialogue: 0,0:02:43.00,0:02:45.02,Default,,0000,0000,0000,,I am actually a really impatient person --
Dialogue: 0,0:02:45.04,0:02:48.84,Default,,0000,0000,0000,,but this, the most important step,\Nworked faster than I dreamed,
Dialogue: 0,0:02:49.84,0:02:51.04,Default,,0000,0000,0000,,basically immediately.
Dialogue: 0,0:02:52.64,0:02:54.86,Default,,0000,0000,0000,,On a weekend in 2014,
Dialogue: 0,0:02:54.88,0:02:57.96,Default,,0000,0000,0000,,a graduate student in my lab\Ngrew bacteria with six-letter DNA.
Dialogue: 0,0:02:58.80,0:03:01.78,Default,,0000,0000,0000,,Let me take the opportunity\Nto introduce you to them right now.
Dialogue: 0,0:03:01.80,0:03:03.44,Default,,0000,0000,0000,,This is an actual picture of them.
Dialogue: 0,0:03:04.88,0:03:07.32,Default,,0000,0000,0000,,These are the first\Nsemisynthetic organisms.
Dialogue: 0,0:03:09.48,0:03:12.26,Default,,0000,0000,0000,,So bacteria with six-letter DNA,\Nthat's really cool, right?
Dialogue: 0,0:03:12.28,0:03:14.72,Default,,0000,0000,0000,,Well, maybe some of you\Nare still wondering why.
Dialogue: 0,0:03:15.68,0:03:18.86,Default,,0000,0000,0000,,So let me tell you a little bit more\Nabout some of our motivations,
Dialogue: 0,0:03:18.88,0:03:20.82,Default,,0000,0000,0000,,both conceptual and practical.
Dialogue: 0,0:03:20.84,0:03:23.54,Default,,0000,0000,0000,,Conceptually, people have\Nthought about life, what it is,
Dialogue: 0,0:03:23.56,0:03:26.18,Default,,0000,0000,0000,,what makes it different\Nfrom things that are not alive,
Dialogue: 0,0:03:26.20,0:03:27.86,Default,,0000,0000,0000,,since people have had thoughts.
Dialogue: 0,0:03:27.88,0:03:30.18,Default,,0000,0000,0000,,Many have interpreted\Nlife as being perfect,
Dialogue: 0,0:03:30.20,0:03:32.70,Default,,0000,0000,0000,,and this was taken\Nas evidence of a creator.
Dialogue: 0,0:03:32.72,0:03:36.38,Default,,0000,0000,0000,,Living things are different\Nbecause a god breathed life into them.
Dialogue: 0,0:03:36.40,0:03:38.74,Default,,0000,0000,0000,,Others have sought\Na more scientific explanation,
Dialogue: 0,0:03:38.76,0:03:40.14,Default,,0000,0000,0000,,but I think it's fair to say
Dialogue: 0,0:03:40.16,0:03:43.06,Default,,0000,0000,0000,,that they still consider\Nthe molecules of life to be special.
Dialogue: 0,0:03:43.08,0:03:46.50,Default,,0000,0000,0000,,I mean, evolution has been optimizing them\Nfor billions of years, right?
Dialogue: 0,0:03:46.52,0:03:49.46,Default,,0000,0000,0000,,Whatever perspective you take,\Nit would seem pretty impossible
Dialogue: 0,0:03:49.48,0:03:51.50,Default,,0000,0000,0000,,for chemists to come in\Nand build new parts
Dialogue: 0,0:03:51.52,0:03:54.54,Default,,0000,0000,0000,,that function within and alongside\Nthe natural molecules of life
Dialogue: 0,0:03:54.56,0:03:56.92,Default,,0000,0000,0000,,without somehow\Nreally screwing everything up.
Dialogue: 0,0:03:58.40,0:04:01.46,Default,,0000,0000,0000,,But just how perfectly\Ncreated or evolved are we?
Dialogue: 0,0:04:01.48,0:04:03.72,Default,,0000,0000,0000,,Just how special\Nare the molecules of life?
Dialogue: 0,0:04:04.64,0:04:06.98,Default,,0000,0000,0000,,These questions have been\Nimpossible to even ask,
Dialogue: 0,0:04:07.00,0:04:09.12,Default,,0000,0000,0000,,because we've had nothing\Nto compare life to.
Dialogue: 0,0:04:10.00,0:04:11.98,Default,,0000,0000,0000,,Now for the first time, our work suggests
Dialogue: 0,0:04:12.00,0:04:14.70,Default,,0000,0000,0000,,that maybe the molecules of life\Naren't that special.
Dialogue: 0,0:04:14.72,0:04:17.76,Default,,0000,0000,0000,,Maybe life as we know it\Nisn't the only way it could be.
Dialogue: 0,0:04:18.92,0:04:22.14,Default,,0000,0000,0000,,Maybe we're not the only solution,\Nmaybe not even the best solution,
Dialogue: 0,0:04:22.16,0:04:23.60,Default,,0000,0000,0000,,just a solution.
Dialogue: 0,0:04:25.60,0:04:28.18,Default,,0000,0000,0000,,These questions address\Nfundamental issues about life,
Dialogue: 0,0:04:28.20,0:04:30.06,Default,,0000,0000,0000,,but maybe they seem a little esoteric.
Dialogue: 0,0:04:30.08,0:04:31.82,Default,,0000,0000,0000,,So what about practical motivations?
Dialogue: 0,0:04:31.84,0:04:34.62,Default,,0000,0000,0000,,Well, we want to explore\Nwhat sort of new stories
Dialogue: 0,0:04:34.64,0:04:36.74,Default,,0000,0000,0000,,life with an expanded\Nvocabulary could tell,
Dialogue: 0,0:04:36.76,0:04:39.98,Default,,0000,0000,0000,,and remember, stories here\Nare the proteins that a cell produces
Dialogue: 0,0:04:40.00,0:04:41.38,Default,,0000,0000,0000,,and the functions they have.
Dialogue: 0,0:04:41.40,0:04:44.50,Default,,0000,0000,0000,,So what sort of new proteins\Nwith new types of functions
Dialogue: 0,0:04:44.52,0:04:48.18,Default,,0000,0000,0000,,could our semisynthetic organisms\Nmake and maybe even use?
Dialogue: 0,0:04:48.20,0:04:50.16,Default,,0000,0000,0000,,Well, we have a couple of things in mind.
Dialogue: 0,0:04:51.24,0:04:55.82,Default,,0000,0000,0000,,The first is to get the cells\Nto make proteins for us, for our use.
Dialogue: 0,0:04:55.84,0:04:57.26,Default,,0000,0000,0000,,Proteins are being used today
Dialogue: 0,0:04:57.28,0:05:00.02,Default,,0000,0000,0000,,for an increasingly broad\Nrange of different applications,
Dialogue: 0,0:05:00.04,0:05:02.30,Default,,0000,0000,0000,,from materials that protect\Nsoldiers from injury
Dialogue: 0,0:05:02.32,0:05:04.54,Default,,0000,0000,0000,,to devices that detect\Ndangerous compounds,
Dialogue: 0,0:05:04.56,0:05:05.90,Default,,0000,0000,0000,,but at least to me,
Dialogue: 0,0:05:05.92,0:05:08.32,Default,,0000,0000,0000,,the most exciting application\Nis protein drugs.
Dialogue: 0,0:05:09.16,0:05:10.58,Default,,0000,0000,0000,,Despite being relatively new,
Dialogue: 0,0:05:10.60,0:05:13.02,Default,,0000,0000,0000,,protein drugs have already\Nrevolutionized medicine,
Dialogue: 0,0:05:13.04,0:05:15.74,Default,,0000,0000,0000,,and, for example, insulin is a protein.
Dialogue: 0,0:05:15.76,0:05:18.62,Default,,0000,0000,0000,,You've probably heard of it,\Nand it's manufactured as a drug
Dialogue: 0,0:05:18.64,0:05:21.30,Default,,0000,0000,0000,,that has completely changed\Nhow we treat diabetes.
Dialogue: 0,0:05:21.32,0:05:24.30,Default,,0000,0000,0000,,But the problem is that proteins\Nare really hard to make
Dialogue: 0,0:05:24.32,0:05:27.92,Default,,0000,0000,0000,,and the only practical way to get them\Nis to get cells to make them for you.
Dialogue: 0,0:05:28.88,0:05:30.58,Default,,0000,0000,0000,,So of course, with natural cells,
Dialogue: 0,0:05:30.60,0:05:34.10,Default,,0000,0000,0000,,you can only get them to make\Nproteins with the natural amino acids,
Dialogue: 0,0:05:34.12,0:05:36.34,Default,,0000,0000,0000,,and so the properties\Nthose proteins can have,
Dialogue: 0,0:05:36.36,0:05:38.86,Default,,0000,0000,0000,,the applications\Nthey could be developed for,
Dialogue: 0,0:05:38.88,0:05:41.38,Default,,0000,0000,0000,,must be limited by the nature\Nof those amino acids
Dialogue: 0,0:05:41.40,0:05:42.90,Default,,0000,0000,0000,,that the protein's built from.
Dialogue: 0,0:05:42.92,0:05:44.14,Default,,0000,0000,0000,,So here they are,
Dialogue: 0,0:05:44.16,0:05:47.42,Default,,0000,0000,0000,,the 20 normal amino acids that are\Nstrung together to make a protein,
Dialogue: 0,0:05:47.44,0:05:50.30,Default,,0000,0000,0000,,and I think you can see,\Nthey're not that different-looking.
Dialogue: 0,0:05:50.32,0:05:52.54,Default,,0000,0000,0000,,They don't bring\Nthat many different functions.
Dialogue: 0,0:05:52.56,0:05:55.22,Default,,0000,0000,0000,,They don't make that many\Ndifferent functions available.
Dialogue: 0,0:05:55.24,0:05:58.82,Default,,0000,0000,0000,,Compare that with the small molecules\Nthat synthetic chemists make as drugs.
Dialogue: 0,0:05:58.84,0:06:00.78,Default,,0000,0000,0000,,Now, they're much simpler than proteins,
Dialogue: 0,0:06:00.80,0:06:04.22,Default,,0000,0000,0000,,but they're routinely built from\Na much broader range of diverse things.
Dialogue: 0,0:06:04.24,0:06:06.18,Default,,0000,0000,0000,,Don't worry about the molecular details,
Dialogue: 0,0:06:06.20,0:06:08.42,Default,,0000,0000,0000,,but I think you can see\Nhow different they are.
Dialogue: 0,0:06:08.44,0:06:11.38,Default,,0000,0000,0000,,And in fact, it's their differences\Nthat make them great drugs
Dialogue: 0,0:06:11.40,0:06:12.78,Default,,0000,0000,0000,,to treat different diseases.
Dialogue: 0,0:06:12.80,0:06:16.98,Default,,0000,0000,0000,,So it's really provocative to wonder\Nwhat sort of new protein drugs
Dialogue: 0,0:06:17.00,0:06:20.36,Default,,0000,0000,0000,,you could develop if you could build\Nproteins from more diverse things.
Dialogue: 0,0:06:21.84,0:06:23.78,Default,,0000,0000,0000,,So can we get our semisynthetic organism
Dialogue: 0,0:06:23.80,0:06:27.02,Default,,0000,0000,0000,,to make proteins that include\Nnew and different amino acids,
Dialogue: 0,0:06:27.04,0:06:29.30,Default,,0000,0000,0000,,maybe amino acids\Nselected to confer the protein
Dialogue: 0,0:06:29.32,0:06:31.40,Default,,0000,0000,0000,,with some desired property or function?
Dialogue: 0,0:06:32.64,0:06:33.90,Default,,0000,0000,0000,,For example,
Dialogue: 0,0:06:33.92,0:06:37.06,Default,,0000,0000,0000,,many proteins just aren't stable\Nwhen you inject them into people.
Dialogue: 0,0:06:37.08,0:06:39.26,Default,,0000,0000,0000,,They are rapidly degraded or eliminated,
Dialogue: 0,0:06:39.28,0:06:41.08,Default,,0000,0000,0000,,and this stops them from being drugs.
Dialogue: 0,0:06:42.08,0:06:44.50,Default,,0000,0000,0000,,What if we could make proteins\Nwith new amino acids
Dialogue: 0,0:06:44.52,0:06:46.34,Default,,0000,0000,0000,,with things attached to them
Dialogue: 0,0:06:46.36,0:06:48.34,Default,,0000,0000,0000,,that protect them from their environment,
Dialogue: 0,0:06:48.36,0:06:51.54,Default,,0000,0000,0000,,that protect them\Nfrom being degraded or eliminated,
Dialogue: 0,0:06:51.56,0:06:53.24,Default,,0000,0000,0000,,so that they could be better drugs?
Dialogue: 0,0:06:55.56,0:06:57.98,Default,,0000,0000,0000,,Could we make proteins\Nwith little fingers attached
Dialogue: 0,0:06:58.00,0:07:00.48,Default,,0000,0000,0000,,that specifically\Ngrab on to other molecules?
Dialogue: 0,0:07:01.48,0:07:04.22,Default,,0000,0000,0000,,Many small molecules\Nfailed during development as drugs
Dialogue: 0,0:07:04.24,0:07:07.18,Default,,0000,0000,0000,,because they just weren't\Nspecific enough to find their target
Dialogue: 0,0:07:07.20,0:07:09.34,Default,,0000,0000,0000,,in the complex environment\Nof the human body.
Dialogue: 0,0:07:09.36,0:07:12.98,Default,,0000,0000,0000,,So could we take those molecules\Nand make them parts of new amino acids
Dialogue: 0,0:07:13.00,0:07:15.78,Default,,0000,0000,0000,,that, when incorporated into a protein,
Dialogue: 0,0:07:15.80,0:07:18.16,Default,,0000,0000,0000,,are guided by that protein\Nto their target?
Dialogue: 0,0:07:20.04,0:07:22.22,Default,,0000,0000,0000,,I started a biotech company\Ncalled Synthorx.
Dialogue: 0,0:07:22.24,0:07:24.86,Default,,0000,0000,0000,,Synthorx stands for synthetic organism
Dialogue: 0,0:07:24.88,0:07:28.54,Default,,0000,0000,0000,,with an X added at the end because\Nthat's what you do with biotech companies.
Dialogue: 0,0:07:28.56,0:07:29.98,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:07:30.00,0:07:32.02,Default,,0000,0000,0000,,Synthorx is working closely with my lab,
Dialogue: 0,0:07:32.04,0:07:36.38,Default,,0000,0000,0000,,and they're interested in a protein\Nthat recognizes a certain receptor
Dialogue: 0,0:07:36.40,0:07:38.10,Default,,0000,0000,0000,,on the surface of human cells.
Dialogue: 0,0:07:38.12,0:07:40.58,Default,,0000,0000,0000,,But the problem is that it also recognizes
Dialogue: 0,0:07:40.60,0:07:43.30,Default,,0000,0000,0000,,another receptor on the surface\Nof those same cells,
Dialogue: 0,0:07:43.32,0:07:44.96,Default,,0000,0000,0000,,and that makes it toxic.
Dialogue: 0,0:07:45.80,0:07:47.94,Default,,0000,0000,0000,,So could we produce\Na variant of that protein
Dialogue: 0,0:07:47.96,0:07:52.30,Default,,0000,0000,0000,,where the part that interacts\Nwith that second bad receptor is shielded,
Dialogue: 0,0:07:52.32,0:07:54.26,Default,,0000,0000,0000,,blocked by something like a big umbrella
Dialogue: 0,0:07:54.28,0:07:57.36,Default,,0000,0000,0000,,so that the protein only interacts\Nwith that first good receptor?
Dialogue: 0,0:07:58.52,0:08:00.26,Default,,0000,0000,0000,,Doing that would be really difficult
Dialogue: 0,0:08:00.28,0:08:02.54,Default,,0000,0000,0000,,or impossible to do\Nwith the normal amino acids,
Dialogue: 0,0:08:02.56,0:08:06.00,Default,,0000,0000,0000,,but not with amino acids that are\Nspecifically designed for that purpose.
Dialogue: 0,0:08:08.52,0:08:11.70,Default,,0000,0000,0000,,So getting our semisynthetic cells\Nto act as little factories
Dialogue: 0,0:08:11.72,0:08:13.22,Default,,0000,0000,0000,,to produce better protein drugs
Dialogue: 0,0:08:13.24,0:08:15.98,Default,,0000,0000,0000,,isn't the only potentially\Nreally interesting application,
Dialogue: 0,0:08:16.00,0:08:19.40,Default,,0000,0000,0000,,because remember, it's the proteins\Nthat allow cells to do what they do.
Dialogue: 0,0:08:20.32,0:08:23.62,Default,,0000,0000,0000,,So if we have cells that make\Nnew proteins with new functions,
Dialogue: 0,0:08:23.64,0:08:27.22,Default,,0000,0000,0000,,could we get them to do things\Nthat natural cells can't do?
Dialogue: 0,0:08:27.24,0:08:30.02,Default,,0000,0000,0000,,For example, could we develop\Nsemisynthetic organisms
Dialogue: 0,0:08:30.04,0:08:34.18,Default,,0000,0000,0000,,that when injected into a person,\Nseek out cancer cells
Dialogue: 0,0:08:34.20,0:08:37.52,Default,,0000,0000,0000,,and only when they find them,\Nsecrete a toxic protein that kills them?
Dialogue: 0,0:08:38.40,0:08:41.34,Default,,0000,0000,0000,,Could we create bacteria\Nthat eat different kinds of oil,
Dialogue: 0,0:08:41.36,0:08:43.26,Default,,0000,0000,0000,,maybe to clean up an oil spill?
Dialogue: 0,0:08:43.28,0:08:45.50,Default,,0000,0000,0000,,These are just a couple\Nof the types of stories
Dialogue: 0,0:08:45.52,0:08:48.78,Default,,0000,0000,0000,,that we're going to see if life\Nwith an expanded vocabulary can tell.
Dialogue: 0,0:08:48.80,0:08:50.30,Default,,0000,0000,0000,,So, sounds great, right?
Dialogue: 0,0:08:50.32,0:08:53.22,Default,,0000,0000,0000,,Injecting semisynthetic\Norganisms into people,
Dialogue: 0,0:08:53.24,0:08:56.62,Default,,0000,0000,0000,,dumping millions and millions of gallons\Nof our bacteria into the ocean
Dialogue: 0,0:08:56.64,0:08:58.14,Default,,0000,0000,0000,,or out on your favorite beach?
Dialogue: 0,0:08:58.16,0:09:00.62,Default,,0000,0000,0000,,Oh, wait a minute,\Nactually it sounds really scary.
Dialogue: 0,0:09:00.64,0:09:02.64,Default,,0000,0000,0000,,This dinosaur is really scary.
Dialogue: 0,0:09:04.48,0:09:06.26,Default,,0000,0000,0000,,But here's the catch:
Dialogue: 0,0:09:06.28,0:09:09.86,Default,,0000,0000,0000,,our semisynthetic organisms\Nin order to survive,
Dialogue: 0,0:09:09.88,0:09:12.80,Default,,0000,0000,0000,,need to be fed the chemical\Nprecursors of X and Y.
Dialogue: 0,0:09:13.80,0:09:17.28,Default,,0000,0000,0000,,X and Y are completely different\Nthan anything that exists in nature.
Dialogue: 0,0:09:18.16,0:09:20.76,Default,,0000,0000,0000,,Cells just don't have them\Nor the ability to make them.
Dialogue: 0,0:09:21.60,0:09:22.86,Default,,0000,0000,0000,,So when we prepare them,
Dialogue: 0,0:09:22.88,0:09:25.82,Default,,0000,0000,0000,,when we grow them up\Nin the controlled environment of the lab,
Dialogue: 0,0:09:25.84,0:09:27.94,Default,,0000,0000,0000,,we can feed them\Nlots of the unnatural food.
Dialogue: 0,0:09:27.96,0:09:31.30,Default,,0000,0000,0000,,Then, when we deploy them\Nin a person or out on a beach
Dialogue: 0,0:09:31.32,0:09:34.02,Default,,0000,0000,0000,,where they no longer\Nhave access that special food,
Dialogue: 0,0:09:34.04,0:09:37.14,Default,,0000,0000,0000,,they can grow for a little bit,\Nthey can survive for a little,
Dialogue: 0,0:09:37.16,0:09:40.66,Default,,0000,0000,0000,,maybe just long enough\Nto perform some intended function,
Dialogue: 0,0:09:40.68,0:09:42.82,Default,,0000,0000,0000,,but then they start\Nto run out of the food.
Dialogue: 0,0:09:42.84,0:09:44.18,Default,,0000,0000,0000,,They start to starve.
Dialogue: 0,0:09:44.20,0:09:46.32,Default,,0000,0000,0000,,They starve to death\Nand they just disappear.
Dialogue: 0,0:09:47.48,0:09:49.90,Default,,0000,0000,0000,,So not only could we get life\Nto tell new stories,
Dialogue: 0,0:09:49.92,0:09:52.92,Default,,0000,0000,0000,,we get to tell life when and where\Nto tell those stories.
Dialogue: 0,0:09:55.08,0:09:58.62,Default,,0000,0000,0000,,At the beginning of this talk\NI told you that we reported in 2014
Dialogue: 0,0:09:58.64,0:10:01.86,Default,,0000,0000,0000,,the creation of semisynthetic organisms\Nthat store more information,
Dialogue: 0,0:10:01.88,0:10:03.98,Default,,0000,0000,0000,,X and Y, in their DNA.
Dialogue: 0,0:10:04.00,0:10:06.46,Default,,0000,0000,0000,,But all the motivations\Nthat we just talked about
Dialogue: 0,0:10:06.48,0:10:08.94,Default,,0000,0000,0000,,require cells to use X and Y\Nto make proteins,
Dialogue: 0,0:10:08.96,0:10:10.64,Default,,0000,0000,0000,,so we started working on that.
Dialogue: 0,0:10:11.60,0:10:15.30,Default,,0000,0000,0000,,Within a couple years, we showed\Nthat the cells could take DNA with X and Y
Dialogue: 0,0:10:15.32,0:10:18.16,Default,,0000,0000,0000,,and copy it into RNA,\Nthe working copy of DNA.
Dialogue: 0,0:10:19.56,0:10:21.38,Default,,0000,0000,0000,,And late last year,
Dialogue: 0,0:10:21.40,0:10:24.54,Default,,0000,0000,0000,,we showed that they could then\Nuse X and Y to make proteins.
Dialogue: 0,0:10:24.56,0:10:27.22,Default,,0000,0000,0000,,Here they are, the stars of the show,
Dialogue: 0,0:10:27.24,0:10:30.72,Default,,0000,0000,0000,,the first fully-functional\Nsemisynthetic organisms.
Dialogue: 0,0:10:31.56,0:10:36.20,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:10:38.04,0:10:41.54,Default,,0000,0000,0000,,These cells are green because\Nthey're making a protein that glows green.
Dialogue: 0,0:10:41.56,0:10:44.10,Default,,0000,0000,0000,,It's a pretty famous protein,\Nactually, from jellyfish
Dialogue: 0,0:10:44.12,0:10:46.22,Default,,0000,0000,0000,,that a lot of people use\Nin its natural form
Dialogue: 0,0:10:46.24,0:10:48.28,Default,,0000,0000,0000,,because it's easy to see that you made it.
Dialogue: 0,0:10:49.28,0:10:51.18,Default,,0000,0000,0000,,But within every one of these proteins,
Dialogue: 0,0:10:51.20,0:10:54.96,Default,,0000,0000,0000,,there's a new amino acid that\Nnatural life can't build proteins with.
Dialogue: 0,0:10:57.16,0:11:01.00,Default,,0000,0000,0000,,Every living cell, every living cell ever,
Dialogue: 0,0:11:02.16,0:11:04.54,Default,,0000,0000,0000,,has made every one of its proteins
Dialogue: 0,0:11:04.56,0:11:06.60,Default,,0000,0000,0000,,using a four-letter genetic alphabet.
Dialogue: 0,0:11:07.72,0:11:11.86,Default,,0000,0000,0000,,These cells are living and growing\Nand making protein
Dialogue: 0,0:11:11.88,0:11:13.78,Default,,0000,0000,0000,,with a six-letter alphabet.
Dialogue: 0,0:11:13.80,0:11:15.20,Default,,0000,0000,0000,,These are a new form of life.
Dialogue: 0,0:11:16.36,0:11:18.52,Default,,0000,0000,0000,,This is a semisynthetic form of life.
Dialogue: 0,0:11:19.84,0:11:21.62,Default,,0000,0000,0000,,So what about the future?
Dialogue: 0,0:11:21.64,0:11:25.22,Default,,0000,0000,0000,,My lab is already working on expanding\Nthe genetic alphabet of other cells,
Dialogue: 0,0:11:25.24,0:11:26.46,Default,,0000,0000,0000,,including human cells,
Dialogue: 0,0:11:26.48,0:11:30.14,Default,,0000,0000,0000,,and we're getting ready to start working\Non more complex organisms.
Dialogue: 0,0:11:30.16,0:11:31.96,Default,,0000,0000,0000,,Think semisynthetic worms.
Dialogue: 0,0:11:33.36,0:11:35.10,Default,,0000,0000,0000,,The last thing I want to say to you,
Dialogue: 0,0:11:35.12,0:11:37.54,Default,,0000,0000,0000,,the most important thing\Nthat I want to say to you,
Dialogue: 0,0:11:37.56,0:11:39.92,Default,,0000,0000,0000,,is that the time\Nof semisynthetic life is here.
Dialogue: 0,0:11:40.76,0:11:42.02,Default,,0000,0000,0000,,Thank you.
Dialogue: 0,0:11:42.04,0:11:46.72,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:11:53.48,0:11:55.98,Default,,0000,0000,0000,,Chris Anderson: I mean,\NFloyd, this is so remarkable.
Dialogue: 0,0:11:56.00,0:11:58.74,Default,,0000,0000,0000,,I just wanted to ask you,
Dialogue: 0,0:11:58.76,0:12:01.26,Default,,0000,0000,0000,,what are the implications of your work
Dialogue: 0,0:12:01.28,0:12:05.14,Default,,0000,0000,0000,,for how we should think\Nabout the possibilities for life,
Dialogue: 0,0:12:05.16,0:12:07.42,Default,,0000,0000,0000,,like, in the universe, elsewhere?
Dialogue: 0,0:12:07.44,0:12:11.58,Default,,0000,0000,0000,,It just seems like so much of life,\Nor so much of our assumptions are based
Dialogue: 0,0:12:11.60,0:12:14.46,Default,,0000,0000,0000,,on the fact that of course,\Nit's got to be DNA,
Dialogue: 0,0:12:14.48,0:12:18.74,Default,,0000,0000,0000,,but is the possibility space\Nof self-replicating molecules
Dialogue: 0,0:12:18.76,0:12:21.86,Default,,0000,0000,0000,,much bigger than DNA,\Neven just DNA with six letters?
Dialogue: 0,0:12:21.88,0:12:24.26,Default,,0000,0000,0000,,Floyd Romesberg:\NAbsolutely, I think that's right,
Dialogue: 0,0:12:24.28,0:12:26.02,Default,,0000,0000,0000,,and I think what our work has shown,
Dialogue: 0,0:12:26.04,0:12:29.74,Default,,0000,0000,0000,,as I mentioned, is that\Nthere's been always this prejudice
Dialogue: 0,0:12:29.76,0:12:31.14,Default,,0000,0000,0000,,that sort of we're perfect,
Dialogue: 0,0:12:31.16,0:12:33.74,Default,,0000,0000,0000,,we're optimal, God created us this way,
Dialogue: 0,0:12:33.76,0:12:35.86,Default,,0000,0000,0000,,evolution perfected us this way.
Dialogue: 0,0:12:35.88,0:12:39.16,Default,,0000,0000,0000,,We've made molecules that work\Nright alongside the natural ones,
Dialogue: 0,0:12:40.44,0:12:43.66,Default,,0000,0000,0000,,and I think that suggests\Nthat any molecules
Dialogue: 0,0:12:43.68,0:12:46.34,Default,,0000,0000,0000,,that obey the fundamental laws\Nof chemistry and physics
Dialogue: 0,0:12:46.36,0:12:47.62,Default,,0000,0000,0000,,and you can optimize them
Dialogue: 0,0:12:47.64,0:12:50.38,Default,,0000,0000,0000,,could do the things that\Nthe natural molecules of life do.
Dialogue: 0,0:12:50.40,0:12:52.14,Default,,0000,0000,0000,,There's nothing magic there.
Dialogue: 0,0:12:52.16,0:12:53.54,Default,,0000,0000,0000,,And I think that it suggests
Dialogue: 0,0:12:53.56,0:12:55.62,Default,,0000,0000,0000,,that life could evolve\Nmany different ways,
Dialogue: 0,0:12:55.64,0:12:58.50,Default,,0000,0000,0000,,maybe similar to us\Nwith other types of DNA,
Dialogue: 0,0:12:58.52,0:13:00.24,Default,,0000,0000,0000,,maybe things without DNA at all.
Dialogue: 0,0:13:01.12,0:13:02.38,Default,,0000,0000,0000,,CA: I mean, in your mind,
Dialogue: 0,0:13:02.40,0:13:05.74,Default,,0000,0000,0000,,how big might that possibility space be?
Dialogue: 0,0:13:05.76,0:13:09.42,Default,,0000,0000,0000,,Do we even know? Are most things going\Nto look something like a DNA molecule,
Dialogue: 0,0:13:09.44,0:13:12.38,Default,,0000,0000,0000,,or something radically different\Nthat can still self-reproduce
Dialogue: 0,0:13:12.40,0:13:14.34,Default,,0000,0000,0000,,and potentially create living organisms?
Dialogue: 0,0:13:14.36,0:13:16.86,Default,,0000,0000,0000,,FR: My personal opinion\Nis that if we found new life,
Dialogue: 0,0:13:16.88,0:13:19.10,Default,,0000,0000,0000,,we might not even recognize it.
Dialogue: 0,0:13:19.12,0:13:22.06,Default,,0000,0000,0000,,CA: So this obsession\Nwith the search for Goldilocks planets
Dialogue: 0,0:13:22.08,0:13:24.50,Default,,0000,0000,0000,,in exactly the right place\Nwith water and whatever,
Dialogue: 0,0:13:24.52,0:13:26.82,Default,,0000,0000,0000,,that's a very parochial\Nassumption, perhaps.
Dialogue: 0,0:13:26.84,0:13:30.26,Default,,0000,0000,0000,,FR: Well, if you want to find someone\Nyou can talk to, then maybe not,
Dialogue: 0,0:13:30.28,0:13:33.18,Default,,0000,0000,0000,,but I think that if you're just\Nlooking for any form of life,
Dialogue: 0,0:13:33.20,0:13:37.10,Default,,0000,0000,0000,,I think that's right, I think that you're\Nlooking for life under the light post.
Dialogue: 0,0:13:37.12,0:13:40.46,Default,,0000,0000,0000,,CA: Thank you for boggling all our minds.\NThank so much, Floyd.
Dialogue: 0,0:13:40.48,0:13:43.12,Default,,0000,0000,0000,,(Applause)