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tv   Speed of Light  CSPAN  November 24, 2013 8:45am-9:51am EST

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he gestures he made it back black suffrage and modern day say well, booth at this moment since i'm going to run lincoln through and this is a lashing out against the possibility of black civil rights. all of that's true, but americans at the time is they receive the news of lincoln's assassination didn't know about the details. so what they assumed was the assassination was a response to the surrender. who's had been infuriated by the south's defeat and he was lashing out against lincoln to rob lincoln of the fruits of his victory. what happened here at appomattox is the context for the assassination in the eyes of almost all northerners. if a site of that. the connection between the surrender of the assassination. they believe booth was trying to undo the union victory at that moment. any other questions? comments?
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>> knowing there's talented leaders in the room. would you want to revive that in some way? something that would fit on a billboard? >> i mean, i think again the myth that the gentleman's agreement between grant and lee is a compelling one and not one that doesn't have merit. it was a great achievement for these two men to end the war. i would like to say parent radically, sometimes people these days we'll talk about a long civil war and appomattox didn't win the war. effectively, appomattox ends the civil war. there are surrenders to come. yes armies in the field, but what happened after appomattox is not going to revive hopes were confederate independence. they die here at appomattox. it is the effective end of the civil war and a great achievement to end the war. this notion of a narrative about
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a gentleman's agreement exists from the very start and even some of these editors like really who were arguing about the terms. there's an air self-congratulation that america ended at civil war and away no country is ever done so before. the gentleman's agreement is rooted in american exceptionalism, how remarkable we are able to end our war without massive executions and reprisals. across the spectrum that impulse to self-congratulation says president, even among people who than express will argue about what the terms really meant. my argument here is nothing that will set clearly on a billboard. i don't think one has to throw out the old billboard so much as remember that the surrender was controversial. how could it not be? 700,000 men have lost their lives. the road to true reconciliation was a very, very difficult one.
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i think to appreciate the meaning of the surrender who lived at this time, we have to remember they let j-juliett grant, the most prestigious men in the country aside from lincoln and after lincoln dies, the two most prestigious men. southerners in northerners look to these meant to represent their respective causes from which so many people lay down their lives in pieces they had in war. they didn't expect these meant to be ends in defeat. they sell them as clients and assumed that's what they would continue to be. part of my argument is land-grant our enemies. how could it be otherwise? it doesn't detract from the achievement of having brought the worst we close. but reminds us these terms down to the cause we don't want to be disturbed and if you disturb us come you broken the covenant. these terms are controversial. i think again sometimes some people are trying to debunk the
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myth, they tell you something you thought was of greater importance is not as greater importance he thought. my purpose is opposite to say it's even more important to say what happens here says the terms for an unfolding debate that we have appreciated. yeah. [inaudible] >> yes, yes. [inaudible] >> i think that's right. really for me, the most surprising discovery of all was et al., with web relish the anti-republican democrats, those copperheads just adopted the confederate bob things. it just shows you how the instant impulse to politicize
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this. my argument if there is never a moment in which northerners and not celebrate grants victory and not very moment when confederates en masse are southerners lament please defeat. it's political from the very start. this has to do them part with the price. what did the traces his followers and here come the campaign, meeting of the clean house from promulgation of the farewell address. i show what happens in the news hits the wires and lands in northern cities and communities and lands in southern cities in the impulse to spin the news is instantaneous for political rivals to try to use it to political advantage. it happens instantly and shows divisions within a society, not just between them. [inaudible] what you are saying is a great, robbery between the usct and
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everyone sending -- [inaudible] begin with each other -- >> that is not. and that was a quote from a postwar race history by george washington williams. the context for these -- african-americans clinked the idea that the surrender is a special moment for them. a moment which they are in the thick terser old in which they are dispensing magnanimity. the context for that is a very long-standing charge that goes back as far as we can trace debates about slavery but if you have emancipation come you're going to have chaos and reprisals and for williams to highlight, i think his account there is somewhat wishful. but it served a political purpose to highlight the possibility of racial record deletion and say that appomattox could symbolize racial reconciliation with an answer to all those who sent us this
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freedom in the victory, there's going to be social chaos, resource the one. williams wanted to allow himself with the forces of progress and civilization and to have decided to magnanimity of african-american at that moment was to do that and offer counter narrative to a dystopian discourse about what would happen if you had read in the union to jury. yes. [inaudible] >> yep, that's right. i don't have a figure they are. really, this is a moment at which they're essentially, you know, the way it's described by sherry dan and others is that we and his men thought the might
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have achieved a breakthrough moment by scattering the union calvary. when they see the infantry en masse in en masse in those woods committee realize their hopes were breakthrough failed. so is the presence of the african-american troops in the sight of union reinforcements that causes the way flex to start going out. indeed, it would be in at the grant and an african-american postwar discourse that black troops fired the shot at lee's army. that is technically not true. but again, it served a purpose in it served a purpose to say we are within the thick or circle and we hope to bring to shield this army that symbolized everything, that symbolizes the very regime that slavery and of the elite. again, to get back to john's question, part of what i'm arguing is that literally happened here is fascinating. i talk about the campaign in a
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lot of detail, but i'm trying to argue appomattox is a much richer symbols and we've realize. it wasn't just a symbol of victory and defeat in vindication of restoration and liberation. functioning on office many levels. [inaudible] >> it was 116, the 27, the 145th. it's all in the book. you got it, good. [inaudible] >> yeah, and one of the regiment waited in the waiting. as one of the marchers and discoveries for me is how many of the men in those armies, not the officers and leaders of the army and later became prominent in referred back to the service very proudly. george washington williams is
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the most important african-american intellectual of this postwar period and he he was there and he considered it very, very important, sort of a key moment in his life, as dissidents and others who would become prominent political leaders. so that's the story. in a way, this is what got me to the project. i've been interested in only ingrained for a long time, but i was asked to music or to give a talk in philadelphia on the subject of juneteenth, the emancipation moment taxes for union forces arrived and announced they are free. in the course of doing research, which was something i knew little about, i kept running across references to appomattox is a freedom day for african-americans. references that dated to the 1930s. the symbolic importance of the place for african-americans persist a really, really long time. sometimes it took the form from chris this out maddux, covering
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the spectrum of african-american military service is eventually does lease for the world wars of the one. but it really lingers as a moment of symbolic importance. it goes beyond things that casualties in who in fact fired glass shards. [inaudible] >> thank you very much. >> my pleasure. [applause] [inaudible conversations] [laughter]
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j. craig venter was the first to sequence the human genome talks about bioengineering and the impact to have an human to future. mr. venter spoke at the national museum of history new york city. this is about an hour and 10 minutes. [applause] >> i could listen to him all night. thank you for the very warm introduction. it's a pleasure to be back at the museum again. pick a comeback last 10 years after they're a part of an exhibit. so it shows how science is changing what we can do. as i'm talking about my new book tonight, "life at the speed of
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light," this is based in no small part on his lecture i was invited to give last year in dublin college, following up on what truly jury did in 1943 when he gave a series of lectures as a physicist trained to define life and see if life had to obey physical principles. and i think he largely concluded that it did. he wrote a book based on his lectures. it is a tiny but did i've read several times. it's called what is life. but it has influenced a tremendous amount of modern science. i want to show you why it has if you haven't read the book. the short answer is because it or saw it the discoveries that have been made over the last almost 70 years at a time when
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people had no idea what the genetic code was or where it was going to go. so his fundamental question, and i start the book with it, is how can the events in space and time that the reason the boundaries of living organisms be accounted for by physics and chemistry? he made a tremendous attempt to answer those questions, but he also hedged a little bit by saying that the inability of them present day science could not explain everything, but that was no reason to doubt that they would eventually be accounted for. ..
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the major form of communication electrically at that time as being sufficient to have a tremendous diversity. so 1944, in his book he came up with this definition talking to the leading biologist of the day, and everybody was sure that dna was too simple of a molecule. it was a simple backbone that helps support a more complex protein that everybody was certain was the basis of inheritance. in reality, it was very wrong but it didn't matter based on
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the assumptions that he was putting forth about the code script. it was also 1944 that the first conclusive experiment took place to, in fact, proved that dna was indeed the genetic material. so there was a very famous experiment that was remarkably simple. they just used a sense of different enzymes and ones that destroyed proteins, destroyed rna and destroy dna to prove that dna was this key transforming factor. but it took a long time for recognition to come to dna. people were ringo -- really focus on proteins, and the first protein was sequenced a few years ago later by fred sanger. and this proved in fact that proteins were a very specific linear sequence. people in this timeframe, in the
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'40s actually thought that proteins were just some sort of boost combination of substances, and not distinct linear chemicals. so obviously the work from watson and crick estimating on the double helix advance the thinking quite a bit because it should have dna could be the template for making copies of itself by unwinding. but even in 1953 when his key paper was published in nature, not a lot of attention was paid to this paper. it really took a while and it wasn't until the 1960s, using some of the first uses of synthetic dna molecules worked out what the dna code was an out
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triplet letters coded for different amino acids. at this stage it was really clear that dna was the genetic material, and a lot of other transformation experiments have been done convincing people at the same time. but after 1960 when things started to move forward much more rapidly in our understanding, bob holly worked out the sequence of trna. pee rna is a key molecule that actually brings in each amino acid one at a time for the synthesis of proteins. so these discoveries linked together to things, a huge step forward. the next decade actually brought the first stages of recombinant dna, start to make changes, and the key discovery, one of the key discoveries that enable this
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was one that my friend and colleague at the institute made, discovering the first restriction enzyme. these three gentlemen shared the nobel prize in 1978 for their discovery. but a number of people were able to take these new tools and use them for some pretty dramatic purposes. i described that not only did dna change in the 1970s, but so did dress codes. [laughter] so this was an early photo right after they made their first recombinant dna experiments work. and rapidly developing this to have a human insulin be produced out of a bacteria which was the basis of genentech getting going and the whole biotech industry taking off.
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genomics still advanced pretty slowly and it wasn't until 1976 that the first genome was sequenced, and it was a small rna virus. the first dna genome was again by fred sanger's team, and it was a key genome that we will come back to come a little over 5000 letters of genetic code, and this was considered a major breakthrough and fred sanger kite's second nobel prize for sequencing this genome and developing a new sequencing technology, now refer to as sanger sequencing, that came without. it was another 18 year gap though between we could go from small viruses to the genome of a living organism. that's what my team accomplished at the institute in 1995, and this is -- is to sure how fast
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things are going, so we went from 5000 letters of genetic code to 1.8 million letters, and it was only five years later that, in fact, were able to scale up using this whole genome shotgun technique to do the entire human genome. so we went from 1.8 million to 3 billion letters of genetic code in a massive effort. when we read the genetic code and put that data in a computer, i described as digitizing biology. and, obviously, we've been doing this for quite a while now of taking the four letter code and converting it into ones and zeros in the computer. we been a chelating more and more of this data over time, and an understanding the fundamental basis of heredity, going back to that code script.
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the same time that all these advances were taking place in the dna world we were getting a better and more complete understanding of the protein world. in this history of proteins, they came up with what i thought every apt description of proteins as natures robots. these are the instruments where genetic programs are transferred from the linear dna code to the linear protein code, but contained within the protein code is all the instructions for how they fold, how stable they are and what they did to everybody is i'm sure very similar with the variety, types of proteins that make up our bodies and make up the living world we see around us. and these have wide ranging set of characteristics from very elastic proteins to very strong
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structural proteins to our muscle proteins, transporters, et cetera. but these proteins have those functions built into their linear code and they don't have any master controllers other than that code. and just to show you how recent some of these findings are, so this is from 2005 where the complete high resolution structure of the bacterial ribosome was determined to. this is, if there's a fundamental motor for life as the co-prescribed, our work is change one of the engines or motors, this is probably one of the most important motor in the south, because this is where -- cell, this is where the linear code is converted into proteins. so appreciating these as complex three-dimensional structures i think it's very important. protein folding is an area
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that's taken quite a while to understand, and we're still in the process of doing it. it took the blue gene computer at ibm to actually do a complete energy compilation for the folding of a single protein. so contained within a typical protein of 100 amino acids there somewhere between -- of possible confirmations. so is each protein that we make in a matter of seconds had to try all these combinations, it would take about 10 million years to go through that process. but, in fact, because we have one of the most important physical principles that was discovered early on called brownie in motion, these processes happened within thousands of a second. so brownie in motion was named after robert brown when he noticed that looking at paula
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molecules under the microscope that they had this ability to move around quite randomly. but it took about 75 years until einstein came along to action show that this movement that we see in looking under any microscope is due to the water molecules and in the states and how they are constantly moving. so light is driven by this basic physical robbery of molecules but it's driven by brownian motion. we always see pictures of dna and proteins in the static forms. but they are actually constantly jigging -- jiggling and rotating and spinning and people have described it as the equivalent of magnitude nine earthquake going on constantly inside your cells. when you think about the evolution of processes, and a lot of our biological systems are like simple gears and
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motors, because of this tremendous energy and shaking and movement, you would have to have a dear that goes forward. so to be like i'm trying to ride a bicycle as long as a with the backwards you would never have to battle. so just to show you one example of modeling that has been done of six microseconds, here's an extended period looking at a longer period of a small peptide. this is what the final confirmation is but you will see it going from the linear code, this takes several seconds but when it happens in reality, that's happening in six microseconds. that's what proteins are like in the cell. that's what dna is like. it's constantly moving and shaking, and this energy allows proteins, based on their linear code, to form into the final confirmation that has the lowest energy state and gives them
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their stable function. they are constantly moving. they are not looking like the in state. and so it's very dynamic and if you could look inside each cell you would see this constant shaking and moving, energy transfer. also built into the linear code from the dna to the protein is something that determined the absolute stability of each protein. it's called the in role of degradation. because how fast approaching will be broken down and turn over. proteins turn over in a matter of seconds to minutes. most people don't realize how dynamic each of our 100 early in cells our or 200 trillion bacterial cells are. they are changing from second to second because they are reading the code and giving us information. if you take the dna out of the
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cell, cells will die a very quickly. protein turnover is probably the single most important biological process because of all this shaking and brownie motion, proteins and they've been very unstable. and if you can't constantly making new ones, cells will die. and if you can't degrade proteins, this is not new york city, but new york city has looked this way at times. when the trash stops being hauled away it's aching legs and it causes things to become an operative. our cells and our bodies and our brains work the same way but, in fact, there's a lot of mis- folding diseases where the proteins are not trafficked out normally. cystic fibrosis, one of the most widely genetic disorders, is due to a letter changed in the
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fluoride ion channel but people thought he just affected its function. in fact, what it affects is the finding of one of the chaperones and how it folds. it never gets folded properly so you never get enough produces so there's less protein in the cell. so all our cells work on the process of dynamic renew. if you can't read the genetic code and possibly make proteins, death results frequently. so even looking at human cells, for example, tumor cells, the half-life of all the cells buried from 45 minutes to a little under 24 hours. each of us shed around 500 million skin cells every day. that dust that's in your house, that's you. and you wonder why you keep getting more dust?
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he shared the entire outer layer of your skin every two to four weeks. the same with our intestinal cells. the same with our blood cells. they have to die and be replaced everybody. even during normal development of a child, 50% of the cells died during a normal organ develop and. so every aspect of human life that's going on behind what we see as individuals at the cellular level is a constant dynamic renewal. so we concluded that our cells, all cells on the planet, our dna driven machines. all driven from the linear dna code that code for the linear protein code, and within that code is all the information that determines the function, the folding rate and their breakdown. but we wanted to prove, and
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waller came up with the notion of synthesis of proof. in fact, he was the one credited with disproving vitalism when he synthesized urea in 1828. and urea was not supposed be able to be made chemically because it was determined to be something that could only come from life, and this change was the start of a changing of a lot of thinking with scientific evidence. if you look in the chemical literature, there's thousands of papers published each year where the title is proved by synthesis. so we decided to try this approach with proving that dna was necessary and sufficient for all the information for life and the way we decide to go about this was to start with the binary code in the computer,
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design a dna molecule, naked from four bottles of chemicals and then find a way to boost it. so the middle part of the book describes his journey going from the digital code back to the genetic code and we're trying to answer a multitude of questions, fairly fundamental ones. what are the minimal number of genes required for life? could we actually define life based on a set of genes or gene functions? and could we design and construct a genome our self? at the time we started this, even making dna molecules 1000 letters long was a herculean task. so we weren't sure that chemistry would allow making these incredibly large molecules in the order of 1 million letters of genetic code, and we didn't know even if we could make the chemical dna, could we
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boot it up in a cell, or which is have a large chemical? we started down the road of synthesis, and we started where sanger did by making the 174 genome. so we started with the sequence that tried to have published in 1977. hutchinson who joined her team was actually a visiting scientist in sanger is not at the time, was a co-author on the paper. the reason we chose this come it had a relatively small genome and is known that it would not take a lot of variation in its genetic code and still get a virus. so we designed how to make this by making small pieces of dna and putting them together with unique methods to make the 5000 letter keys of dna. the exciting face connect. we injected this into e. coli
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and the exciting thing is e. coli community started to read this piece of synthetic dna. it started making proteins. the proteins self assemble to form the virus and after millions of copies of virus are made in each cell, the virus showed his gratitude by killing the cells which is how we detected. that is played is e. coli bacteria every place you see those clear spots is whether was a massive amount of virus released killing additional cells. so we called this a situation where the software builds its own hardware or we just put in a piece of dna chemical software into the cell, and what we got out of it was these viral particles that can infect other e. coli cells and make a lot more copies. our goal was not just to make a small virus. we wanted to make an entire
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genome of a self-replicating organism, but we thought if we could at least make a small bible pieces of dna accurately, we might find a way to put them all together to make the entire chromosome so we started down this road. it took more than a few years to do this. each stage having to invent the techniques that didn't exist before. we decided, the genome of a very small bacteria into 101%, all around the size of the virus and was are making these cassettes one at a time. and then tried to put them together to make larger and larger pieces. so action looks like a final four playoff, that sort of how it came about. we put four of the 6000 letter pieces together to get pieces that were 24,000 letters long. and each stage we had to grow these u up and e. coli make a lt of it been a, sequence it to make sure we're not introducing
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new errors, purify it and then go on to a symbol that with its neighbors to get to the next size. you can see why this would be very laborious going to this end we had a whole team doing nothing but this for over a year. so we headed through the space of together, we get pieces that were 72000 letters long. at this stage we more than doubled the world record highs number one team it spent a long time, several years, making a piece that was 30,000 letters long of that was the largest piece of dna that had ever been made. then we went to the next stage. we put two of those together, pieces that were one quarter of the genome into 144,000 base pairs in length. but at this stage when we put these large pieces of synthetic into e. coli, the e. coli didn't like these large pieces we looked around for a new system and we found the -- where we get
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wine and beer and bread from so the staple of the american diet would take these large pieces of dna and actually put them together. so it uses a process where the sequences match up that will put them together. so we put these four quarter genome tomato fuels on their own -- molecules and just a small vector so we could isolate it and yeast automatically put all these pieces together. the resulting chromosome was the first synthetic bacterial chromosome. we reported this in 2008, and at the time this was the largest molecule of define substance ever made before, because it was such a large linear sequence. the team continued to improve our ability to assemble dna.
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we hired a young person who made a major breakthrough by taking these complicated steps that we all did individually, and he found he could do them all together in a single test tube at a constant temperature, 50 degrees centigrade. this one step reaction that makes it very simple just to put small pieces of dna into this tested, incubated for a little bit and then you get the assembled piece of dna out of it. we named the process in his honor and is referred to as the gibson assembly. you can even find youtube songs about it from students that were very grateful to have this new simplified method. and what it means, aside from the simplicity of it, means we can now automate this process which would change the scale that we could produce synthetic dna molecules.
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so while the chemistry was improving, i formed another team to look at the biology. how would we boot up a chromosome? we could do it like we did with the virus. because it infects dna on its own. so we had a team working for quite a while on it and john glass and carol worked together can lead his team in which a major breakthrough in 2007 at in the book i described this in some detail because this set of experiments had more to do with my understanding of how life works, and they think it's affecting other people in the same way. basically, we transplanted a genome from one cell to another species, and in the process of doing that convert the one species into the other. because this is so fundamental to understand how synthetic biology works and synthetic
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genomics, and how your cells work as well, i will walk you through this a little bit. we had two species of mycoplasma. these are small bacterial cells, self-replicating cells, and these two species are about as close to each other as mice and humans are. so a little over 10% different. we isolated the chromosome and we did what avery did 60 years earlier. we treated partially to remove all proteins because we wanted to find out if we just made chemically naked dna that it would work, and there wasn't some proteins required for transplantation. we added to cassettes to. one so we could select for it with an antibiotic and another it would turn cells bright blue if this genome was activated. we came up with all kinds of ways to transplant it into these
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recipient cells tiki can actually -- large chromosomes are very brittle so it actually had to develop techniques for moving these around little gel blocks and at the last minute we is an enzyme to dissolve the gel and move it into the cell. so we have the full movie that i would show you of what we think happened. is a very sophisticated movie. [laughter] so we added the chromosome to the cell and now we have an unusual situation. we have two sets of genetic software in the cell. what we think happened as soon as we put the new chromosome in the cell, like with the file next genome, it's been they started being read, it's are producing proteins right away. some of these proteins included the restriction enzymes that actually recognize the dean as for indian a and chewed it up.
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so now we have the body and the type of one species and the genetic software of another species. so what happened? in a very short put a time we ended up with these bright blue cells, and when we interrogated them they had only the dna that we transplanted, and all the counter mistakes of the other so the we put the dna into work on. this cell by any and all measurements was now -- this is very critical and historical understanding evolution because it helps show that dna software, life is a dna software system, and that if you change the software you change the species. this is put into context, in fact, why restriction enzymes evolve in the first place. because if you're a bacterial
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species and you want to maintain your species lineage, and any old piece of chromosome could come along, enter your cell and take over and convert you to something else, it's like to get a fish dinner tonight come you into changing your cells into efficient cells. evolution would be a really messy process. so restriction enzymes are how cells defend themselves against foreign dna coming in. they chewed it up so they can maintain their own species. but lots of times and evolution there's been a mismatch in what those restriction enzymes recognize. lots of cells that we find when we sequenced genomes out of the ocean for example, have multiple chromosomes and they clearly have different lineages. a lot of people think about evolution happening one little genetic change at a time. but, in fact, it can happen thousands of genes at a time and whole sets of functions come along in a single step.
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so we had a unique problem in that we were, our synthesis program used yeast to do the final assembly of the synthetic dna. so we have to find a way to isolate the synthetic dna out of yeast to do the transplant. and to work this out, our team worked how to clone entire bacterial chromosomes in the eukaryotic cell. this is been successful now with a lot of different microbial species with a remarkably simple step. we just take a east centromere. when you see pictures of chromosome with a why, the centromere is that little junction peace and it helps, is essential for chromosomes being transported probably in the so when they're being replicated. simply adding a small artificial east centromere to bacterial chromosome appears to convert it stably into a eukaryotic chromosome. so when you think about complex
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steps in evolution, it could've been that simple going from a pro-kerry got to eukaryotic. so now we have a system where we have to try to isolate the chromosome out of yeast into a transplant. and when we did this we had a major problem but it didn't work. and this problem took the team over two years to solve and the reason for it is the bacterial systems to protect themselves from their own restriction enzymes, eukaryotic cells like east have different systems so this dna was essentially different. the way we saw this is we isolated the sixth different genes from the cell and if we methylated again after isolate it from east we could do successful genome plant and --
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transplantations again. we ultimately proved it by removing the restriction enzyme genes from the recipient cell. in that case we could make dna out of yeast. but these steps show you that none of these processes in science are just straightforward linear processes. we hit roadblock like this and they set you back sometimes for years. but the techniques that we derive from this are pretty remarkable because they allow us to do things that weren't possible to even consider doing in science before. so simply adding a yeast art official sentiment to a chromosome we can now -- most bacteria systems are not able to be studied because they are not genetic tools to work with them. but as soon as we put the bacterial chromosome in yeast, we had the entire yeast genetics
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including recombination which allows for very rapid changes to occur, to make a lot of changes in that back to chromosome. we can isolate it, methylated if necessary, transplanted into recipient cell and would work our way around the circle making a very rapid changes. if this method already exist we probably wouldn't have gone down the route of trying to make synthetic dna in the first place, but it's a potential very useful tool. so now we decided we had all these new synthetic components. we solve the transplantation to we isolated the chromosome out of yeast and get successful transplants, and we decided, i cover this in the book, it took quite a bit of convincing for me to convince the team to abandon working on a much smaller chromosome, and to make the much larger genome. so this was 1.1 million base pairs. but this went very fast with the
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new gibson assembly and our technology. so we started with pieces that were 1000 letters long. we put 10 of those together to make pieces over 10,000 letters long. they would put 10 of those together to make pieces that were 100,000 letters long. until we had 11 of these major cassettes that we've been putting to yeast to assume the entire chromosome. we have this done. we were already to do the major transplantation experiment. we were sure it was going to work. nothing happened. there were no successful transplants. our controls worked by the synthetic genome out of yeast didn't work. so we knew there was something wrong with our code or with are designed, and so we did what software engineers do. they hav have debugging softwaro find out what errors are in theiin thesoftware code. so we developed a biological debugging system where we could take each of these hundred
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thousand letter pieces one at a time and put them back into the controlled genome to see if they so ported life. and it turns out 10 of them did, the last one didn't. and so we we sequenced once again the last 100 segments. we sequenced it before but we were using new nextgen technology and one of the problems with all the new technologists is they make systematic errors. it looks like a perfect sequence but sometimes it's just perfectly wrong. so we went back and sequenced it with sanger sequencing and we found a single letter dilution in a key gene. so we corrected that sequence, we made the entire chromosome, did the transplantation, and two days later we had the first synthetic sal.
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we knew it was a synthetic cell because we could isolate the dna and sequenced it. and in 2010 this was the cover of science with our synthetic cells on the cover. what we have put in to prove it was we developed a new code to write the entire english language with numbers and punctuation in the dna code. we had watermarked the first genome we made but which is just a single i mean the acid code which doesn't cover the entire alphabet. so in this we have the names of the 46 scientists that took part in this over the several year period it. we have a code in the first watermarked. it looks like it's a little buggy so i'm not sure it shows up, but the first watermarked tell you how to decode the rest. so that was the secret decoder ring to it being the first genome whose parent was a computer, this has a url built into its genetic code.
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you are instructed to you could decode it to send e-mail to the species at that e-mail address. saying that should successively decoded it. once a number of people had worked this out, we posted the entire translation. and in addition to the names of the institutions and the scientists, i decided to add three quotations from the literature that i thought were appropriate for the occasion. the first was from james joyce, to live, to air, default, to triumph, to re-create life out of life. that seemed highly relevant. the second was from oppenheimer's biography. in his case talking about developing the atom bomb, but more forward-looking, see things not as they are but as they might be. trying to be optimistic. and the third was from richard
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heineman, what i cannot build i cannot understand. so we were quite happy with this and with all the press on it. the first response we got was a letter from james joyce attorneys the state, a state attorney, asking if we had permission to use the quotation. james joyce was bid. we weren't -- we could do miracles but we couldn't do that one. and also under u.s. copyright law you can use up to a paragraph with attribution without permission. so we didn't worry about that one too much. then we started getting e-mails from caltech scientist thing we misquoted richard heineman, was also dead and couldn't correct it. and we challenge this because if you look on the internet, this is essential to quote you find over and over again, and were
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asked his guide to validate it and so he sent us a picture from the caltech archives of feynman's blackboard when the original quote was written. and i think it's a much better quotation. what i cannot create i do not understand. it's part of this whole notion of proof by synthesis and if you can't replicate it by building it, you clearly don't understand it. so we acknowledge this, and went back and changed the genetic code in the genome so that richard feynman will rest peacefully with the proper quotation. but what's coming next? you know, this was a proof of principle. we show that we could actually go from the digital world back to the biological were. we could make it. with a transplant it. and so what comes next is now the applications and what of the questions we constantly got, what does the salad you that you made?
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itself replicates, billions of times and it can metabolize sugars and make everything it needs for life from the chemicals. i thought that was pretty good. it didn't have any practical application. so we've been working for a long time now both at the institute and at synthetic genomics giving computer software to design new dna software. this is taking us in lots of different directions. we are close but not there yet on a completely computer designed cell that has about half the jeans of mycoplasma and we been working by knocking out genes trying to understand the biology to design a genome based on first principles of what a cell needs. the problem is even with this
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minimal cell, 50 of the genes in the cell that required for life of unknown function. so by trying to design a jet or an automobile engine with 50 key parts, but all you do is you -- is if you leave out those parts it won't work. so our biology is sort of a limiting step in real design. so there's this integral part of this field that is ongoing, and but as we get further and further down this road we will -- were trying to solve a lot of unique problems and one we decide to focus on early on is finding a way that makes much faster vaccines. with the h1n1 flu pandemic, fortunately it was far lighter than anybody expected, but we
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didn't have a vaccine and joe two months after it had peaked and around 25 -- a total of 250,000 people died, either very young people are very old people because they were in the range that word covered by other vaccines. so we tried synthetically to change this process it and also we were looking for things where we could use the unique properties of the interchange the 20 digital and biological world's. i use this as an example because if we can send dna as an electromagnetic wave as ones and zeros, reconstituted, we could get samples to and from mars in as little as 4.3 minutes the end of the road are martians that are bringing them back on a rocket ship, we can beam them back and reconstitute them in a secure lab instead of having them splashed down in the ocean,
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which ruins all the and dramatists scenarios for people but it's probably still the right way to do it. so we call this new area biological teleportation. and it relies on this rapid interplay between the dna software and the digital world. and so we can actually send a life at the speed of light and we converted at the other end back into biology. so we're doing this in two processes. we were going to be doing it a few weeks ago until government shutdown. we have unit testing with the help of nasa and we're going to test it out their mars test site out in the california desert, and the mahdi desert, where we're going to isolate soil microbes, sequence them and beating them up to the club. -- mojave desert. we been working with help of darpa on the other in which we call it digital biological in order that can convert that
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signal back into proteins, viruses or single bacterial cells. there's lots of applications we can see with this, for example, sending like we did with phi x, through the computer, or sending a flu virus through the computer and making that and using it as a treatment for antibiotic resistant bacteria or in the case of the vaccines of making a new vaccine on the site. we been working for a long time, and we've made the first gene encased vaccine. it's against meningitis b., this vaccine just came out earlier this year. is a 17 year process, mostly the length of clinical trials but the first truly new major vaccine to come along in a long
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time. 17 years is a long time and, obviously, that won't work for flu pandemics. so with the flu we try to change the time course and this is what it's important that the last time there was a major, major pandemic about 3% of the world's population was killed by the 1918 flu virus. this virus has been recovered from people died from the flu in 1918 and were buried in the permafrost, so they were still full of live flu virus. it was sequenced and reconstructed and we can understand some of the differences from it. but now my institute is part of a worldwide surveillance program using dna sequence and essentially sending units like were describing from mars to sequence dna in different outbreaks and send it up to the cloud or on the web for constant tracking. we have sequenced 10,000 or so
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virus isolates. but recently this got a real world test with the outbreak of h. seven in nine in china. the chinese that are part of the surveillance program sequence this virus right away and post it on the internet. we downloaded the digital information in a very short time had a synthetic version of h. seven and nine virus and for quite a while this was the only source of virus that the cdc had an part of the government had to even study this new emerging strain. and novartis is in the process of creating a vaccine for this well in advance in case of, this spreads are rapidly. this has a much higher without a than a flu virus, h1n1. we have the first version and we
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actually have one that requires manual intervention at the site in novartis, and the other advancement novartis made was annually to make the flu virus for all of us that requires in the u.s. alone around 900 million eggs. but novartis just got approved from the fda to use a cell line, to produce the flu vaccine. so at this site in north carolina we have a converter where we can just send an e-mail message with a new flu sequence. it gets me very quickly and starts down the line for making production. but if one site works, why not have more sites? maybe one in each country, maybe one in each city. those of you hav who've seen the movie contagion have sort of seeing a hypothetical version of
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what would happen today with a major flu outbreak, equivalent to the 1918 flu. so if these were distributed around, we could respond very quickly to a new outbreak. and my ultimate version is we'll have a box on our home computers where you can download the vaccine from the internet and not have to leave your home and get contaminated. and these devices will change a little bit how we view the internet, if all of a sudden instead of just getting digital information, you could download biology from the internet. it's pretty straightforward. for example, with our device to download insulin. see you can quickly convert the dna into any direction. so insulin, vaccines are all
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within the realm, at least theoretical potential. it's not clear -- well, it is clear. the fda probably won't like this process, because it kind of democratizes who has access to things, much the way the internet has done. but if some of the potential. from the very beginning we've asked our own ethical questions, asked for our review, is it okay to create new life in the lab that hasn't existed before. lots of studies have now been published, but first one from the university, from penn state, from university of pennsylvania was published in science in 1999, and i discussed some of these things extensively in the book. when we announced in 2010 our first synthetic cell, as it obama asked to take this on an
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issue this report in december of that year and you can download this from the white house website. interesting. i think for a government report, i couldn't have asked for a better job. they talk about the strengths and the potential and some of the dangers with this. should be deregulated, should it not be, and talks about new things in science that should be funded, for example, to put kill switches into synthetic organisms so they can't survive outside the lab. so i think this is government committees -- at best been watched very carefully and you can get the more complete version of this. enjoyed at your leisure. thank you very much. [applause]


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