[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:01.01,0:00:02.42,Default,,0000,0000,0000,,All life,
Dialogue: 0,0:00:02.42,0:00:04.12,Default,,0000,0000,0000,,every living thing ever,
Dialogue: 0,0:00:04.12,0:00:07.44,Default,,0000,0000,0000,,has been built according\Nto the information in DNA.
Dialogue: 0,0:00:07.44,0:00:08.60,Default,,0000,0000,0000,,What does that mean?
Dialogue: 0,0:00:08.60,0:00:10.99,Default,,0000,0000,0000,,Well, it means that just\Nas the English language
Dialogue: 0,0:00:10.99,0:00:14.25,Default,,0000,0000,0000,,is made up of alphabetic letters\Nthat, when combined into words,
Dialogue: 0,0:00:14.25,0:00:16.93,Default,,0000,0000,0000,,allow me to tell you the story\NI'm going to tell you today,
Dialogue: 0,0:00:16.93,0:00:21.15,Default,,0000,0000,0000,,DNA is made up of genetic letters\Nthat, when combined into genes,
Dialogue: 0,0:00:21.15,0:00:23.38,Default,,0000,0000,0000,,allow cells to produce proteins,
Dialogue: 0,0:00:23.38,0:00:26.42,Default,,0000,0000,0000,,strings of amino acids that fold up\Ninto complex structures
Dialogue: 0,0:00:26.42,0:00:29.57,Default,,0000,0000,0000,,that perform the functions\Nthat allow a cell to do what it does,
Dialogue: 0,0:00:29.57,0:00:31.31,Default,,0000,0000,0000,,to tell its stories.
Dialogue: 0,0:00:31.31,0:00:35.06,Default,,0000,0000,0000,,The English alphabet has 26 letters,\Nand the genetic alphabet has four.
Dialogue: 0,0:00:35.06,0:00:36.67,Default,,0000,0000,0000,,They're pretty famous.\NMaybe you've heard of them.
Dialogue: 0,0:00:36.67,0:00:40.98,Default,,0000,0000,0000,,They are often just referred to\Nas G, C, A and T.
Dialogue: 0,0:00:40.98,0:00:44.27,Default,,0000,0000,0000,,But it's remarkable that all\Nthe diversity of life
Dialogue: 0,0:00:44.27,0:00:47.57,Default,,0000,0000,0000,,is the result of four genetic letters.
Dialogue: 0,0:00:47.57,0:00:51.59,Default,,0000,0000,0000,,Imagine what it would be like\Nif the English alphabet had four letters.
Dialogue: 0,0:00:51.59,0:00:55.56,Default,,0000,0000,0000,,What sort of stories\Nwould you be able to tell?
Dialogue: 0,0:00:55.56,0:00:58.72,Default,,0000,0000,0000,,What if the genetic alphabet\Nhad more letters?
Dialogue: 0,0:00:58.72,0:01:02.70,Default,,0000,0000,0000,,Would life with more letters\Nbe able to tell different stories,
Dialogue: 0,0:01:02.70,0:01:06.91,Default,,0000,0000,0000,,maybe even more interesting ones?
Dialogue: 0,0:01:06.91,0:01:10.70,Default,,0000,0000,0000,,In 1999, my lab at the Scripps\NResearch Institute in La Jolla, California
Dialogue: 0,0:01:10.70,0:01:14.22,Default,,0000,0000,0000,,started working on this question\Nwith the goal of creating living organisms
Dialogue: 0,0:01:14.22,0:01:17.56,Default,,0000,0000,0000,,with DNA made up of\Na six-letter genetic alphabet,
Dialogue: 0,0:01:17.56,0:01:23.50,Default,,0000,0000,0000,,the four natural letters plus two\Nadditional new man-made letters.
Dialogue: 0,0:01:23.72,0:01:27.22,Default,,0000,0000,0000,,Such an organism would be the first\Nradically altered form of life
Dialogue: 0,0:01:27.22,0:01:27.65,Default,,0000,0000,0000,,ever created.
Dialogue: 0,0:01:27.65,0:01:31.74,Default,,0000,0000,0000,,It would be a semi-synthetic form of life\Nthat stores more information
Dialogue: 0,0:01:31.74,0:01:34.43,Default,,0000,0000,0000,,than life ever has before.
Dialogue: 0,0:01:34.43,0:01:36.32,Default,,0000,0000,0000,,It would be able to make new proteins,
Dialogue: 0,0:01:36.32,0:01:38.91,Default,,0000,0000,0000,,proteins built from more\Nthan the 20 normal amino acids
Dialogue: 0,0:01:38.91,0:01:41.77,Default,,0000,0000,0000,,that are usually used to build proteins.
Dialogue: 0,0:01:41.77,0:01:44.79,Default,,0000,0000,0000,,What sort of stories could that life tell?
Dialogue: 0,0:01:44.79,0:01:48.89,Default,,0000,0000,0000,,With the power of synthetic chemistry\Nand molecular biology
Dialogue: 0,0:01:48.89,0:01:50.30,Default,,0000,0000,0000,,and just under 20 years of work,
Dialogue: 0,0:01:50.30,0:01:52.67,Default,,0000,0000,0000,,we created bacteria with six-letter DNA.
Dialogue: 0,0:01:52.67,0:01:54.87,Default,,0000,0000,0000,,Let me tell you how we did it.
Dialogue: 0,0:01:54.87,0:01:57.02,Default,,0000,0000,0000,,All you have to remember\Nfrom your high school biology
Dialogue: 0,0:01:57.02,0:01:59.33,Default,,0000,0000,0000,,is that the four natural letters\Npair together to form two base pairs.
Dialogue: 0,0:01:59.33,0:02:03.33,Default,,0000,0000,0000,,G pairs with C and A pairs with T,
Dialogue: 0,0:02:03.33,0:02:05.88,Default,,0000,0000,0000,,so to create our new letters,
Dialogue: 0,0:02:05.88,0:02:08.83,Default,,0000,0000,0000,,we synthesize hundreds of new candidates,\Nnew candidate letters,
Dialogue: 0,0:02:08.83,0:02:11.80,Default,,0000,0000,0000,,and examined their abilities\Nto selectively pair with each other.
Dialogue: 0,0:02:11.80,0:02:16.02,Default,,0000,0000,0000,,And after about 15 years of work, we found\Ntwo that paired together really well,
Dialogue: 0,0:02:16.02,0:02:17.84,Default,,0000,0000,0000,,at least in a test tube.
Dialogue: 0,0:02:17.84,0:02:20.54,Default,,0000,0000,0000,,They have complicated names,
Dialogue: 0,0:02:20.54,0:02:22.31,Default,,0000,0000,0000,,but let's just called X and Y.
Dialogue: 0,0:02:22.31,0:02:25.58,Default,,0000,0000,0000,,The next thing we needed to do\Nwas find a way to get X and Y into cells,
Dialogue: 0,0:02:25.58,0:02:28.87,Default,,0000,0000,0000,,and eventually we found that a protein\Nthat does something similar in algae
Dialogue: 0,0:02:28.87,0:02:30.69,Default,,0000,0000,0000,,worked in our bacteria.
Dialogue: 0,0:02:30.69,0:02:32.85,Default,,0000,0000,0000,,So the final thing that we needed to do\Nwas to show that with X and Y provided,
Dialogue: 0,0:02:32.85,0:02:34.99,Default,,0000,0000,0000,,cells could grow and divide\Nand hold on to X and Y in their DNA.
Dialogue: 0,0:02:34.99,0:02:37.47,Default,,0000,0000,0000,,Everything we had done up to then\Ntook longer than I had hoped --
Dialogue: 0,0:02:37.47,0:02:44.93,Default,,0000,0000,0000,,I am actually a really impatient person --
Dialogue: 0,0:02:44.93,0:02:46.59,Default,,0000,0000,0000,,but this, the most important step,\Nworked faster than I dreamed,
Dialogue: 0,0:02:46.59,0:02:51.65,Default,,0000,0000,0000,,basically immediately.
Dialogue: 0,0:02:51.65,0:02:55.20,Default,,0000,0000,0000,,On a weekend in 2014,
Dialogue: 0,0:02:55.20,0:02:58.99,Default,,0000,0000,0000,,a graduate student in my lab\Ngrew bacteria with six-letter DNA.
Dialogue: 0,0:02:58.99,0:03:01.62,Default,,0000,0000,0000,,Let me take the opportunity\Nto introduce you to them right now.,
Dialogue: 0,0:03:01.62,0:03:04.21,Default,,0000,0000,0000,,This is an actual picture of them.
Dialogue: 0,0:03:04.21,0:03:09.06,Default,,0000,0000,0000,,These are the first\Nsemi-synthetic organisms.
Dialogue: 0,0:03:09.06,0:03:12.63,Default,,0000,0000,0000,,So bacteria with six-letter DNA,\Nthat's really cool, right?
Dialogue: 0,0:03:12.63,0:03:15.74,Default,,0000,0000,0000,,Well, maybe some of you\Nare still wondering why.
Dialogue: 0,0:03:15.74,0:03:18.32,Default,,0000,0000,0000,,So let me tell you a little bit more\Nabout some of our motivations,
Dialogue: 0,0:03:18.32,0:03:21.07,Default,,0000,0000,0000,,both conceptual and practical.
Dialogue: 0,0:03:21.07,0:03:23.86,Default,,0000,0000,0000,,Conceptually, people have\Nthought about life, what it is,
Dialogue: 0,0:03:23.86,0:03:25.94,Default,,0000,0000,0000,,what makes it different\Nfrom things that are not alive,
Dialogue: 0,0:03:25.94,0:03:28.19,Default,,0000,0000,0000,,since people have had thoughts.
Dialogue: 0,0:03:28.19,0:03:31.01,Default,,0000,0000,0000,,Many have interpreted\Nlife as being perfect,
Dialogue: 0,0:03:31.01,0:03:33.04,Default,,0000,0000,0000,,and this was taken\Nas evidence of a creator.
Dialogue: 0,0:03:33.04,0:03:36.46,Default,,0000,0000,0000,,Living things are different\Nbecause a god breathed life into them.
Dialogue: 0,0:03:36.46,0:03:38.77,Default,,0000,0000,0000,,Others have sought\Na more scientific explanation,
Dialogue: 0,0:03:38.77,0:03:42.72,Default,,0000,0000,0000,,but I think it's fair to say
Dialogue: 0,0:03:42.72,0:03:43.39,Default,,0000,0000,0000,,that they still consider\Nthe molecules of life to be special.
Dialogue: 0,0:03:43.39,0:03:46.58,Default,,0000,0000,0000,,I mean, evolution has been optimizing them\Nfor billions of years, right?
Dialogue: 0,0:03:46.58,0:03:48.89,Default,,0000,0000,0000,,Whatever perspective you take,\Nit would seem pretty impossible
Dialogue: 0,0:03:48.89,0:03:51.05,Default,,0000,0000,0000,,for chemists to come in\Nand build new parts
Dialogue: 0,0:03:51.05,0:03:54.10,Default,,0000,0000,0000,,that function within and alongside\Nthe natural molecules of life
Dialogue: 0,0:03:54.10,0:03:58.12,Default,,0000,0000,0000,,without somehow really\Nscrewing everything up.
Dialogue: 0,0:03:58.12,0:04:01.76,Default,,0000,0000,0000,,But just how perfectly\Ncreated or evolved are we?
Dialogue: 0,0:04:01.76,0:04:04.90,Default,,0000,0000,0000,,Just how special\Nare the molecules of life?
Dialogue: 0,0:04:04.90,0:04:06.99,Default,,0000,0000,0000,,These questions have been\Nimpossible to even ask,
Dialogue: 0,0:04:06.99,0:04:10.33,Default,,0000,0000,0000,,because we've had nothing\Nto compare life to.
Dialogue: 0,0:04:10.33,0:04:13.25,Default,,0000,0000,0000,,Now for the first time, our work suggests\Nthat maybe the molecules of life
Dialogue: 0,0:04:13.25,0:04:15.01,Default,,0000,0000,0000,,aren't that special.
Dialogue: 0,0:04:15.01,0:04:19.31,Default,,0000,0000,0000,,Maybe life as we know it\Nisn't the only way it could be.
Dialogue: 0,0:04:19.31,0:04:22.17,Default,,0000,0000,0000,,Maybe we're not the only solution,\Nmaybe not even the best solution,
Dialogue: 0,0:04:22.17,0:04:25.22,Default,,0000,0000,0000,,just a solution.
Dialogue: 0,0:04:25.22,0:04:28.55,Default,,0000,0000,0000,,These questions address\Nfundamental issues about life,
Dialogue: 0,0:04:28.55,0:04:30.08,Default,,0000,0000,0000,,but maybe they seem a little esoteric.
Dialogue: 0,0:04:30.08,0:04:31.62,Default,,0000,0000,0000,,So what about practical motivations?
Dialogue: 0,0:04:31.62,0:04:34.59,Default,,0000,0000,0000,,Well, we want to explore\Nwhat sort of new stories
Dialogue: 0,0:04:34.59,0:04:36.93,Default,,0000,0000,0000,,life with an expanded\Nvocabulary could tell,
Dialogue: 0,0:04:36.93,0:04:40.29,Default,,0000,0000,0000,,and remember, stories here\Nare the proteins that a cell produces
Dialogue: 0,0:04:40.29,0:04:41.71,Default,,0000,0000,0000,,and the functions they have.
Dialogue: 0,0:04:41.71,0:04:44.41,Default,,0000,0000,0000,,So what sort of new proteins\Nwith new types of functions
Dialogue: 0,0:04:44.41,0:04:48.47,Default,,0000,0000,0000,,could our semi-synthetic organisms\Nmake and maybe even use?
Dialogue: 0,0:04:48.47,0:04:51.48,Default,,0000,0000,0000,,Well, we have a couple of things in mind.
Dialogue: 0,0:04:51.48,0:04:56.15,Default,,0000,0000,0000,,The first is to get the cells\Nto make proteins for us, for our use.
Dialogue: 0,0:04:56.15,0:04:58.32,Default,,0000,0000,0000,,Proteins are being used today
Dialogue: 0,0:04:58.32,0:05:00.05,Default,,0000,0000,0000,,for an increasingly broad\Nrange of different applications,
Dialogue: 0,0:05:00.05,0:05:02.48,Default,,0000,0000,0000,,from materials that protect\Nsoldiers from injury
Dialogue: 0,0:05:02.48,0:05:04.83,Default,,0000,0000,0000,,to devices that detect\Ndangerous compounds,
Dialogue: 0,0:05:04.83,0:05:06.01,Default,,0000,0000,0000,,but at least to me,
Dialogue: 0,0:05:06.01,0:05:09.00,Default,,0000,0000,0000,,the most exciting application\Nis protein drugs.
Dialogue: 0,0:05:09.42,0:05:10.85,Default,,0000,0000,0000,,Despite being relatively new,
Dialogue: 0,0:05:10.85,0:05:13.08,Default,,0000,0000,0000,,protein drugs have already\Nrevolutionized medicine,
Dialogue: 0,0:05:13.08,0:05:15.97,Default,,0000,0000,0000,,and for example insulin is a protein.
Dialogue: 0,0:05:15.97,0:05:18.57,Default,,0000,0000,0000,,You've probably heard of it,\Nand it's manufactured as a drug
Dialogue: 0,0:05:18.57,0:05:21.41,Default,,0000,0000,0000,,that has completely changed\Nhow we treat diabetes.
Dialogue: 0,0:05:21.41,0:05:24.53,Default,,0000,0000,0000,,But the problem is is that proteins\Nare really hard to make,
Dialogue: 0,0:05:24.53,0:05:28.50,Default,,0000,0000,0000,,and the only practical way to get them\Nis to get cells to make them for you.
Dialogue: 0,0:05:28.50,0:05:32.48,Default,,0000,0000,0000,,So of course, with natural cells,\Nyou can only get them to make
Dialogue: 0,0:05:32.48,0:05:34.52,Default,,0000,0000,0000,,proteins with the natural amino acids,
Dialogue: 0,0:05:34.52,0:05:36.54,Default,,0000,0000,0000,,and so the properties\Nthose proteins can have,
Dialogue: 0,0:05:36.54,0:05:38.68,Default,,0000,0000,0000,,the applications they\Ncould be developed for,
Dialogue: 0,0:05:38.68,0:05:41.52,Default,,0000,0000,0000,,must be limited by the nature\Nof those amino acids
Dialogue: 0,0:05:41.52,0:05:43.19,Default,,0000,0000,0000,,that the protein's built from.
Dialogue: 0,0:05:43.19,0:05:44.36,Default,,0000,0000,0000,,So here they are,
Dialogue: 0,0:05:44.36,0:05:47.17,Default,,0000,0000,0000,,the 20 normal amino acids that are\Nstrung together to make a protein,
Dialogue: 0,0:05:47.17,0:05:50.07,Default,,0000,0000,0000,,and I think you can see, they're\Nnot that different-looking.
Dialogue: 0,0:05:50.07,0:05:51.85,Default,,0000,0000,0000,,They don't bring\Nthat many different functions.
Dialogue: 0,0:05:51.85,0:05:53.92,Default,,0000,0000,0000,,They don't make that many\Ndifferent functions available.
Dialogue: 0,0:05:53.92,0:05:58.16,Default,,0000,0000,0000,,Compare that with the small molecules\Nthat synthetic chemists make as drugs.
Dialogue: 0,0:05:58.16,0:06:00.87,Default,,0000,0000,0000,,Now, they're much simpler than proteins,
Dialogue: 0,0:06:00.87,0:06:03.83,Default,,0000,0000,0000,,but they're routinely built from\Na much broader range of diverse things.
Dialogue: 0,0:06:03.83,0:06:05.49,Default,,0000,0000,0000,,Don't worry about the molecular details,
Dialogue: 0,0:06:05.49,0:06:07.54,Default,,0000,0000,0000,,but I think you can see\Nhow different they are.
Dialogue: 0,0:06:07.54,0:06:10.82,Default,,0000,0000,0000,,And in fact, it's their differences\Nthat make them great drugs
Dialogue: 0,0:06:10.82,0:06:12.96,Default,,0000,0000,0000,,to treat different diseases.
Dialogue: 0,0:06:12.96,0:06:17.17,Default,,0000,0000,0000,,So it's really provocative to wonder\Nwhat sort of new protein drugs
Dialogue: 0,0:06:17.17,0:06:21.33,Default,,0000,0000,0000,,you could develop if you could build\Nproteins from more diverse things.
Dialogue: 0,0:06:21.33,0:06:23.99,Default,,0000,0000,0000,,So can we get our semi-synthetic organism
Dialogue: 0,0:06:23.99,0:06:27.34,Default,,0000,0000,0000,,to make proteins that include\Nnew and different amino acids,
Dialogue: 0,0:06:27.34,0:06:29.44,Default,,0000,0000,0000,,maybe amino acids selected\Nto confer the protein
Dialogue: 0,0:06:29.44,0:06:31.88,Default,,0000,0000,0000,,with some desired property or function?
Dialogue: 0,0:06:31.88,0:06:34.23,Default,,0000,0000,0000,,For example,
Dialogue: 0,0:06:34.23,0:06:37.32,Default,,0000,0000,0000,,many proteins just aren't stable\Nwhen you inject them into people.
Dialogue: 0,0:06:37.32,0:06:40.46,Default,,0000,0000,0000,,They are rapidly degraded or eliminated,
Dialogue: 0,0:06:40.46,0:06:42.02,Default,,0000,0000,0000,,and this stops them from being drugs.
Dialogue: 0,0:06:42.02,0:06:44.36,Default,,0000,0000,0000,,What if we could make proteins\Nwith new amino acids
Dialogue: 0,0:06:44.36,0:06:45.99,Default,,0000,0000,0000,,with things attached to them
Dialogue: 0,0:06:45.99,0:06:48.54,Default,,0000,0000,0000,,that protect them from their environment,
Dialogue: 0,0:06:48.54,0:06:51.62,Default,,0000,0000,0000,,that protect them from\Nbeing degraded or eliminated,
Dialogue: 0,0:06:51.62,0:06:54.06,Default,,0000,0000,0000,,so that they could be better drugs?
Dialogue: 0,0:06:54.06,0:06:58.02,Default,,0000,0000,0000,,Could we make proteins\Nwith little fingers attached
Dialogue: 0,0:06:58.02,0:07:01.07,Default,,0000,0000,0000,,that specifically grab on\Nto other molecules?
Dialogue: 0,0:07:01.07,0:07:04.24,Default,,0000,0000,0000,,Many small molecules fail\Nduring development as drugs
Dialogue: 0,0:07:04.24,0:07:07.01,Default,,0000,0000,0000,,because they just weren't\Nspecific enough to find their target
Dialogue: 0,0:07:07.01,0:07:09.53,Default,,0000,0000,0000,,in the complex environment\Nof the human body.
Dialogue: 0,0:07:09.53,0:07:13.18,Default,,0000,0000,0000,,So could we take those molecules\Nand make them parts of new amino acids
Dialogue: 0,0:07:13.18,0:07:15.41,Default,,0000,0000,0000,,that, when incorporated into a protein,
Dialogue: 0,0:07:15.41,0:07:18.89,Default,,0000,0000,0000,,are guided by that protein\Nto their target?
Dialogue: 0,0:07:20.14,0:07:22.58,Default,,0000,0000,0000,,I started a biotech company\Ncalled Synthorx.
Dialogue: 0,0:07:22.58,0:07:25.09,Default,,0000,0000,0000,,Synthorx stands for synthetic organism
Dialogue: 0,0:07:25.09,0:07:28.80,Default,,0000,0000,0000,,with an X added at the end because\Nthat's what you do with biotech companies.
Dialogue: 0,0:07:28.80,0:07:30.24,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:07:30.24,0:07:32.55,Default,,0000,0000,0000,,Synthorx is working closely with my lab,
Dialogue: 0,0:07:32.55,0:07:36.63,Default,,0000,0000,0000,,and they're interested in a protein\Nthat recognizes a certain receptor
Dialogue: 0,0:07:36.63,0:07:38.40,Default,,0000,0000,0000,,on the surface of human cells.
Dialogue: 0,0:07:38.40,0:07:40.80,Default,,0000,0000,0000,,But the problem is that it also recognizes
Dialogue: 0,0:07:40.80,0:07:43.64,Default,,0000,0000,0000,,another receptor on the surface\Nof those same cells,
Dialogue: 0,0:07:43.64,0:07:46.06,Default,,0000,0000,0000,,and that makes it toxic.
Dialogue: 0,0:07:46.06,0:07:48.07,Default,,0000,0000,0000,,So could we produce\Na variant of that protein
Dialogue: 0,0:07:48.07,0:07:52.21,Default,,0000,0000,0000,,where the part that interacts\Nwith that second bad receptor is shielded,
Dialogue: 0,0:07:52.21,0:07:55.57,Default,,0000,0000,0000,,blocked by something like a big umbrella\Nso that the protein only interacts
Dialogue: 0,0:07:55.57,0:07:57.75,Default,,0000,0000,0000,,with that first good receptor?
Dialogue: 0,0:07:57.75,0:07:59.94,Default,,0000,0000,0000,,Doing that would be really difficult
Dialogue: 0,0:07:59.94,0:08:02.19,Default,,0000,0000,0000,,or impossible to do\Nwith the normal amino acids,
Dialogue: 0,0:08:02.19,0:08:06.22,Default,,0000,0000,0000,,but not with amino acids that are\Nspecifically designed for that purpose.
Dialogue: 0,0:08:06.22,0:08:11.82,Default,,0000,0000,0000,,So getting our semi-synthetic cells\Nto act as little factories
Dialogue: 0,0:08:11.82,0:08:13.28,Default,,0000,0000,0000,,to produce better protein drugs
Dialogue: 0,0:08:13.28,0:08:15.94,Default,,0000,0000,0000,,isn't the only potentially\Nreally interesting application,
Dialogue: 0,0:08:15.94,0:08:19.95,Default,,0000,0000,0000,,because remember, it's the proteins\Nthat allow cells to do what they do.
Dialogue: 0,0:08:19.95,0:08:23.80,Default,,0000,0000,0000,,So if we have cells that make\Nnew proteins with new functions,
Dialogue: 0,0:08:23.80,0:08:27.49,Default,,0000,0000,0000,,could we get them to do things\Nthat natural cells can't do?
Dialogue: 0,0:08:27.49,0:08:30.35,Default,,0000,0000,0000,,For example, could we develop\Nsemi-synthetic organisms
Dialogue: 0,0:08:31.22,0:08:33.09,Default,,0000,0000,0000,,that when injected into a person
Dialogue: 0,0:08:33.09,0:08:35.61,Default,,0000,0000,0000,,seek out cancer cells\Nand only when they find them
Dialogue: 0,0:08:35.61,0:08:38.50,Default,,0000,0000,0000,,secrete a toxic protein that kills them?
Dialogue: 0,0:08:38.50,0:08:41.63,Default,,0000,0000,0000,,Could we create bacteria\Nthat eat different kinds of oil,
Dialogue: 0,0:08:41.63,0:08:43.58,Default,,0000,0000,0000,,maybe to clean up an oil spill?
Dialogue: 0,0:08:43.58,0:08:45.91,Default,,0000,0000,0000,,These are just a couple\Nof the types of stories
Dialogue: 0,0:08:45.91,0:08:48.75,Default,,0000,0000,0000,,that we're going to see if life\Nwith an expanded vocabulary can tell.
Dialogue: 0,0:08:48.75,0:08:50.28,Default,,0000,0000,0000,,So, sounds great, right?
Dialogue: 0,0:08:50.28,0:08:53.49,Default,,0000,0000,0000,,Injecting semi-synthetic\Norganisms into people,
Dialogue: 0,0:08:53.49,0:08:56.71,Default,,0000,0000,0000,,dumping millions and millions of gallons\Nof our bacteria into the ocean
Dialogue: 0,0:08:56.71,0:08:58.39,Default,,0000,0000,0000,,or out on your favorite beach?
Dialogue: 0,0:08:58.39,0:09:00.78,Default,,0000,0000,0000,,Oh, wait a minute,\Nactually it sounds really scary.
Dialogue: 0,0:09:00.78,0:09:04.34,Default,,0000,0000,0000,,This dinosaur is really scary.
Dialogue: 0,0:09:04.75,0:09:06.49,Default,,0000,0000,0000,,But here's the catch:
Dialogue: 0,0:09:06.49,0:09:10.10,Default,,0000,0000,0000,,our semi-synthetic organisms\Nin order to survive
Dialogue: 0,0:09:10.10,0:09:14.10,Default,,0000,0000,0000,,need to be fed the chemical\Nprecursors of X and Y.
Dialogue: 0,0:09:14.10,0:09:17.76,Default,,0000,0000,0000,,X and Y are completely different\Nthan anything that exists in nature.
Dialogue: 0,0:09:17.76,0:09:21.75,Default,,0000,0000,0000,,Cells just don't have them\Nor the ability to make them.
Dialogue: 0,0:09:21.75,0:09:23.22,Default,,0000,0000,0000,,So when we prepare them,
Dialogue: 0,0:09:23.22,0:09:24.95,Default,,0000,0000,0000,,when we grow them up in\Nthe controlled environment of the lab,
Dialogue: 0,0:09:24.95,0:09:27.61,Default,,0000,0000,0000,,we can feed them lots\Nof the unnatural food.
Dialogue: 0,0:09:27.61,0:09:31.60,Default,,0000,0000,0000,,Then, when we deploy them\Nin a person or out on a beach
Dialogue: 0,0:09:31.60,0:09:34.32,Default,,0000,0000,0000,,where they no longer\Nhave access that special food,
Dialogue: 0,0:09:34.32,0:09:36.38,Default,,0000,0000,0000,,they can grow for a little bit,
Dialogue: 0,0:09:36.38,0:09:37.67,Default,,0000,0000,0000,,they can survive for a little,
Dialogue: 0,0:09:37.67,0:09:41.03,Default,,0000,0000,0000,,maybe just long enough to perform\Nsome intended function,
Dialogue: 0,0:09:41.03,0:09:43.15,Default,,0000,0000,0000,,but then they start\Nto run out of the food.
Dialogue: 0,0:09:43.15,0:09:44.56,Default,,0000,0000,0000,,They start to starve.
Dialogue: 0,0:09:44.56,0:09:47.78,Default,,0000,0000,0000,,They starve to death,\Nand they just disappear.
Dialogue: 0,0:09:47.78,0:09:50.23,Default,,0000,0000,0000,,So not only could we get life\Nto tell new stories,
Dialogue: 0,0:09:50.23,0:09:54.12,Default,,0000,0000,0000,,we get to tell life when and where\Nto tell those stories.
Dialogue: 0,0:09:54.12,0:09:58.71,Default,,0000,0000,0000,,At the beginning of this talk\NI told you that we reported in 2014
Dialogue: 0,0:09:58.71,0:10:02.22,Default,,0000,0000,0000,,the creation of semi-synthetic organisms\Nthat store more information,
Dialogue: 0,0:10:02.22,0:10:04.08,Default,,0000,0000,0000,,X and Y, in their DNA.
Dialogue: 0,0:10:04.08,0:10:06.40,Default,,0000,0000,0000,,But all the motivations\Nthat we just talked about
Dialogue: 0,0:10:06.40,0:10:09.34,Default,,0000,0000,0000,,require cells to use X and Y\Nto make proteins,
Dialogue: 0,0:10:09.34,0:10:11.96,Default,,0000,0000,0000,,so we started working on that.
Dialogue: 0,0:10:11.96,0:10:15.64,Default,,0000,0000,0000,,Within a couple years, we showed\Nthat the cells could take DNA with X and Y
Dialogue: 0,0:10:15.64,0:10:17.29,Default,,0000,0000,0000,,and copy it into RNA,\Nthe working copy of DNA.
Dialogue: 0,0:10:17.29,0:10:20.97,Default,,0000,0000,0000,,And late last year,
Dialogue: 0,0:10:20.97,0:10:24.71,Default,,0000,0000,0000,,we showed that they could then\Nuse X and Y to make proteins.
Dialogue: 0,0:10:24.71,0:10:27.14,Default,,0000,0000,0000,,Here they are, the stars of the show,
Dialogue: 0,0:10:27.14,0:10:31.63,Default,,0000,0000,0000,,the first fully-functional\Nsemi-synthetic organisms.
Dialogue: 0,0:10:31.63,0:10:35.07,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:10:37.15,0:10:41.17,Default,,0000,0000,0000,,These cells are green because\Nthey're making a protein that glows green.
Dialogue: 0,0:10:41.17,0:10:43.91,Default,,0000,0000,0000,,It's a pretty famous protein\Nactually from jellyfish
Dialogue: 0,0:10:43.91,0:10:46.07,Default,,0000,0000,0000,,that a lot of people use\Nin its natural form
Dialogue: 0,0:10:46.07,0:10:49.03,Default,,0000,0000,0000,,because it's easy to see that you made it.
Dialogue: 0,0:10:49.03,0:10:51.41,Default,,0000,0000,0000,,But within every one of these proteins,
Dialogue: 0,0:10:51.41,0:10:56.95,Default,,0000,0000,0000,,there's a new amino acid that\Nnatural life can't build proteins with.
Dialogue: 0,0:10:56.95,0:11:02.17,Default,,0000,0000,0000,,Every living cell, every living cell ever,
Dialogue: 0,0:11:02.17,0:11:04.82,Default,,0000,0000,0000,,has made every one of its proteins
Dialogue: 0,0:11:04.82,0:11:07.97,Default,,0000,0000,0000,,using a four-letter genetic alphabet.
Dialogue: 0,0:11:07.97,0:11:12.12,Default,,0000,0000,0000,,These cells are living and growing\Nand making protein
Dialogue: 0,0:11:12.12,0:11:14.09,Default,,0000,0000,0000,,with a six-letter alphabet.
Dialogue: 0,0:11:14.09,0:11:16.54,Default,,0000,0000,0000,,These are a new form of life.
Dialogue: 0,0:11:16.54,0:11:20.07,Default,,0000,0000,0000,,This is a semi-synthetic form of life.
Dialogue: 0,0:11:20.07,0:11:21.93,Default,,0000,0000,0000,,So what about the future?
Dialogue: 0,0:11:21.93,0:11:24.86,Default,,0000,0000,0000,,My lab is already working on expanding \Nthe genetic alphabet of other cells,
Dialogue: 0,0:11:24.86,0:11:26.38,Default,,0000,0000,0000,,including human cells,
Dialogue: 0,0:11:26.38,0:11:29.84,Default,,0000,0000,0000,,and we're getting ready to start working\Non more complex organisms.
Dialogue: 0,0:11:29.84,0:11:33.51,Default,,0000,0000,0000,,Think semi-synthetic worms.
Dialogue: 0,0:11:33.51,0:11:35.52,Default,,0000,0000,0000,,The last thing I want to say to you,
Dialogue: 0,0:11:35.52,0:11:37.80,Default,,0000,0000,0000,,the most important thing\Nthat I want to say to you,
Dialogue: 0,0:11:37.80,0:11:40.86,Default,,0000,0000,0000,,is that the time\Nof semi-synthetic life is here.
Dialogue: 0,0:11:40.86,0:11:42.38,Default,,0000,0000,0000,,Thank you.
Dialogue: 0,0:11:42.38,0:11:44.91,Default,,0000,0000,0000,,(Applause)
Dialogue: 0,0:11:50.44,0:11:55.90,Default,,0000,0000,0000,,Chris Anderson: I mean, Floyd,\Nthis is so remarkable.
Dialogue: 0,0:11:55.90,0:11:57.82,Default,,0000,0000,0000,,I just wanted to ask you,
Dialogue: 0,0:11:57.82,0:12:01.14,Default,,0000,0000,0000,,what are the implications of your work
Dialogue: 0,0:12:01.14,0:12:03.54,Default,,0000,0000,0000,,for how we should think about
Dialogue: 0,0:12:03.54,0:12:05.93,Default,,0000,0000,0000,,the possibilities for life,
Dialogue: 0,0:12:05.93,0:12:07.87,Default,,0000,0000,0000,,like, in the universe, elsewhere?
Dialogue: 0,0:12:07.87,0:12:10.03,Default,,0000,0000,0000,,It just seems like so much of life,\Nor so much of our assumptions are based
Dialogue: 0,0:12:10.03,0:12:14.60,Default,,0000,0000,0000,,on the fact that of course\Nit's got to be DNA,
Dialogue: 0,0:12:14.60,0:12:19.05,Default,,0000,0000,0000,,but is the possibility space\Nof self-replicating molecules
Dialogue: 0,0:12:19.05,0:12:22.19,Default,,0000,0000,0000,,much bigger than DNA,\Neven just DNA with six letters?
Dialogue: 0,0:12:22.19,0:12:24.09,Default,,0000,0000,0000,,Floyd Romesberg: Absolutely,\NI think that's right,
Dialogue: 0,0:12:24.09,0:12:26.76,Default,,0000,0000,0000,,and I think what our work has shown,\Nas I mentioned, is that I think that
Dialogue: 0,0:12:26.76,0:12:30.77,Default,,0000,0000,0000,,there's been always this prejudice\Nthat sort of we're perfect,
Dialogue: 0,0:12:30.77,0:12:33.69,Default,,0000,0000,0000,,and we're optimal,\NGod created us this way,
Dialogue: 0,0:12:33.69,0:12:36.17,Default,,0000,0000,0000,,evolution perfected us this way.
Dialogue: 0,0:12:36.17,0:12:39.86,Default,,0000,0000,0000,,We've made molecules that work\Nright alongside the natural ones,
Dialogue: 0,0:12:39.86,0:12:43.82,Default,,0000,0000,0000,,and I think that suggests\Nthat any molecules
Dialogue: 0,0:12:43.82,0:12:46.76,Default,,0000,0000,0000,,that obey the fundamental laws\Nof chemistry and physics
Dialogue: 0,0:12:46.76,0:12:48.58,Default,,0000,0000,0000,,and you can optimize them
Dialogue: 0,0:12:48.58,0:12:50.38,Default,,0000,0000,0000,,could do the things that\Nthe natural molecules of life do.
Dialogue: 0,0:12:50.38,0:12:52.44,Default,,0000,0000,0000,,There's nothing magic there.
Dialogue: 0,0:12:52.44,0:12:54.08,Default,,0000,0000,0000,,And I think that it suggests
Dialogue: 0,0:12:54.08,0:12:55.78,Default,,0000,0000,0000,,that life could evolve\Nmany different ways,
Dialogue: 0,0:12:55.78,0:12:58.80,Default,,0000,0000,0000,,maybe similar to us\Nwith other types of DNA,
Dialogue: 0,0:12:58.80,0:13:00.94,Default,,0000,0000,0000,,maybe things without DNA at all.
Dialogue: 0,0:13:00.94,0:13:02.64,Default,,0000,0000,0000,,CA: I mean, in your mind,
Dialogue: 0,0:13:02.64,0:13:06.06,Default,,0000,0000,0000,,how big might that possibility space be?
Dialogue: 0,0:13:06.06,0:13:08.100,Default,,0000,0000,0000,,Do we even know? Are most things going\Nto look something like a DNA molecule,
Dialogue: 0,0:13:08.100,0:13:12.79,Default,,0000,0000,0000,,or something radically different\Nthat can still potentially self-reproduce
Dialogue: 0,0:13:12.79,0:13:14.28,Default,,0000,0000,0000,,and potentially create living organisms?
Dialogue: 0,0:13:14.28,0:13:16.87,Default,,0000,0000,0000,,FR: My personal opinion\Nis that if we found new life,
Dialogue: 0,0:13:16.87,0:13:18.70,Default,,0000,0000,0000,,we might not even recognize it.
Dialogue: 0,0:13:18.70,0:13:22.05,Default,,0000,0000,0000,,CA: So this obsession with the search\Nfor Goldilocks planets
Dialogue: 0,0:13:22.05,0:13:24.65,Default,,0000,0000,0000,,in exactly the right place\Nwith water and whatever,
Dialogue: 0,0:13:24.65,0:13:27.13,Default,,0000,0000,0000,,that's a very parochial\Nassumption, perhaps.
Dialogue: 0,0:13:27.13,0:13:29.47,Default,,0000,0000,0000,,FR: Well, if you want to find something\Nyou can talk to, then maybe not,
Dialogue: 0,0:13:29.47,0:13:33.30,Default,,0000,0000,0000,,but I think that if you're just\Nlooking for any form of life,
Dialogue: 0,0:13:33.30,0:13:37.30,Default,,0000,0000,0000,,I think that's right, I think that you're\Nlooking for life under the light post.
Dialogue: 0,0:13:37.30,0:13:40.88,Default,,0000,0000,0000,,CA: Thank you for boggling\Nall our minds. Thank so much, Floyd.
Dialogue: 0,0:13:40.88,0:13:43.13,Default,,0000,0000,0000,,(Applause)