 This afternoon we've got a great opportunity to engage one of our country's most disruptive thinkers, Craig Venter. Craig Venter is what I call a 4s. It's a rare combination. Swimmer, sailor, surfer, scientist. And you sort of put those four things together and you take enough California stuff and you push it inside him and you give him the experience that he had in the Navy and the experience he's had as an academic, the experience he's had at NIH, the experience he's had as an entrepreneur and you can get a differentiated set of ways in which you think the world might move forward scientifically. So most of you know that Craig was one of the two teams racing to get the genome mapped and won that race, won the National Medal of Science for that effort, has since been advancing whole new ways of conceptualizing synthetic biology. Can we build the organism that we need to create to help us solve our energy issues? A different approach than what Nathan's talking about back there. He's also been involved in with his crews searching for what nature may have given us in the gene pool and he'll probably talk a little bit about that because there's a lot out there, but there certainly isn't the silver bullet that's going to take us to move forward in synthetic ways. And so in Craig what you've got is a disruptor scientist. We've heard this morning from different folks about what it takes for breakthroughs, what it takes for fantastic things to happen. Well, it takes finding mechanisms and places for scientists like Craig Venter to be able to move forward and really make things happen. So it's a great pleasure and honor to introduce Craig Venter. Hello again, everybody. For those of you who were here this morning, I'm Steve Kahl and it's my honor to lead our conversation with Craig. I'm going to move this down a little bit. We'll talk up here for a little while and then we'll invite you to join the conversation when that happens. Please remember to wait for the microphone, identify yourself and remember that we're on the record and we're on the air. So speak appropriately. Craig, well that was a uplifting introduction, the sort we'd all like. If you're a disruptor in the way you think about energy, whether it's power generation or transportation fuels, there's been a lot of conversation here today about where disruptive technologies that are scalable, that could really change the way we produce and consume energy in this country, in this world, are going to come from. So where are they going to come from? Thank Michael for the very kind introduction. I sort of feel like the comedian who just got up here now say something funny. So I'm supposed to say something disruptive, I guess. But biology is one of the areas that's been really overlooked and it's been overlooked in part because people have tried all kinds of experiments over the last 50, 60 years, for example, with algae. And looking for naturally occurring algae to make oils, to make fuels, etc. And it's pretty obvious there's nothing that's going to be in the natural world that produces the kind of levels that are needed to have an impact. Explain why that is. So if, so the best sort of state-of-the-art of a naturally occurring algae facility can produce the equivalent of roughly 2,000 gallons per acre per year, which is far better than any agriculture system. Corn, for example, produces 18 gallons of oil per acre per year. So 2,000 is far better than 18. The best plant is palm oil, oil palm, producing roughly 800 gallons of palm oil per year per acre. But the numbers, yeah. I can stop you for one second for those of us who are not in your field or downstream engineers. Is all of this oil potentially by its nature usable as transportation fueled? So the, well, palm oil is obviously, it's a much better market for food than for fuel and, but people have tried to use it for fuel. So yes, it's all usable in some form or another. The numbers for algae that are theoretically possible are somewhere between 10,000 and 20,000 gallons a year per an acre equivalent. But the thinking has been very linear in this area. And you can find the same kind of algae ponds with raceways, a little paddle wheel moving algae around that people were building as long ago as 100 years ago, without much difference in the technology. People have tried to use various types of cells to produce different chemicals. The biggest change came when DuPont spent 10 years and over a hundred million dollars modifying E. Coli, the bacteria E. Coli to take sugar to propane dial. So sugar is six carbon propane dials, a three carbon unit. And now the bacteria can make it much faster and cheaper than the best chemist can. But at the scale and the time it took them to do that. What years were those roughly? They just put it into production, I think, two and a half years ago in Tennessee with these giant silo fermenters. Right. So without that kind of investment for a single project, we're not going to get very far. So the only way to change things in what's new in biology, well, we spent the last several years getting to the announcement we had last spring of the first synthetic cell. So this cell is the first living organism on this planet to have a parent being a computer. And we designed the DNA based largely on a living system, went from the digital code in the computer to making the DNA software. We made the entire 1.1 million base pair chromosome that we put in a cell and booted it up replacing the chromosome that was in the cell, creating a whole new cell powered totally by this synthetic chemical, the chemically made DNA. So that's the proof of concept for this new field that we're calling synthetic genomics. Where the notion is we can take all this information we've been collecting over the last 20 years in the computer, what I call digitizing biology. So when we sequence your genome or anybody's genome, that converts the four letter A, C, G's and T's into the ones and zeros in the computer. And from our expedition that Michael mentioned, over 95 percent of all the genes known to science have been discovered from the deck of my sailboat, simply by doing a shotgun sequence into the oceans. And we've done complete circumnavigations and have been checking extensively where we are. We're up to about 80 million genes. There were less than a million known when we started. And I call these 80 million genes soon probably to be 200 million. We don't know where discovery on this planet's going to plateau out are the design components of the future. So the same way the electronics industry had resistors and capacitors and transistors for almost everything we have in the electronic world, we have orders of magnitude more design components when you think of gene components as such. So let's take that very well articulated context and bring it into the energy economy, which you've done. And so I want to follow you on. We haven't done it yet. All right, so so just to make this as at the risk of dumbing it down, but I want to make sure everyone understands exactly what the implications of your monologue are for the transportation fuels economy. You're looking for a scalable break breakthrough based in insights from synthetic biology that could replace with perhaps algae derived or synthetic algae derived fuels, a significant part of the gasoline consumption in the United States, if not all of it, that's essentially what you're up to. Now, now take me back to the beginning of your thought process. You obviously have studied some of the past efforts to find a breakthrough with similar oils derived from from plants or food. How did you find your way toward the hypothesis that you're pursuing now with with algae? In other words, where did you begin and then what made you develop confidence about the possibility of the path you're working on? Well, the entire synthetic life program started just by asking very simple basic science questions. So my team in 1995 sequenced the first two genomes in history of relatively small bacteria. You may remember in 1996, some NASA astronauts claim that they found nanobacteria fossils in a Martian meteor. And that started a lot of people. I was one of them thinking about what minimal life was or could be. Turns out these tiny little bubbles were so small you couldn't even have a single molecule of RNA or DNA in them and ultimately NASA retracted the claim. But at this time, we started thinking about minimal life. We had the first two genomes in history. Could we actually get down to understanding what is a core biological operating system that once we had that core operating system, we could add components to it to make virtually anything replacing all potentially of the petrochemical industry and farming. Neither are really in a very efficient way of going about things. People argue that all science that you need today is to overcome the science of the past. Well, 100 years ago, we thought it was such a great idea to take oil out of the ground and use it for things like transportation, not foreseeing what's shown in the Keeling curve of this constant increase of CO2 in the atmosphere since it was first measured. And that increases at an increasing rate now from not just burning oil as fuel, but everything we make of plastics and chemicals. So, also the third organism we discovered came from very deep on a high temperature vent in the ocean. And its metabolism is converting carbon dioxide into methane, and that's how it generates its cellular energy. And it does this at 85 degrees centigrade under extreme pressure. So we started to see the extremes of biology and what was possible. We now have organisms that work in such caustic conditions. If you put your finger in it, your finger would dissolve. But these cells reproduce, live very happily in those. We have organisms that can take high doses of radiation, high temperatures. We have cells that grow at zero degrees. So basically the realm of biology is different than what we thought from this human-centric view of biology. It has to be at 37 degrees or it's not going to work. So by putting all these things together and being able to now start in the computer and take all these components and design something new, my view is if we do that, we can replace the entire system of manufacturing. All right, so then take that forward to the particular problem of algae as a potential transportation fuel or substitute for oil in that respect and others including manufacturer plastics. As you said before, natural algae typically yields 10 to 20,000 gallons an acre. Did I hear that correctly? No, they're maximum around 2,000 gallons an acre. Most of them do a whole lot less. And so in order to compete, what kind of increase by order of magnitude in that productivity would your synthetic algae need to achieve? We need to go from the 2,000 to the 10 to 20,000, so a 5 to 10 fold increase. So that's the goal. But 5 to 10 fold in biology is pretty trivial. We've seen million fold changes in biological reactions from direct alteration of them. So there's about 100 different components we've measured that go into converting CO2 and sunlight into these large change hydrocarbons that could affect things. You might even say why algae? Well, there's a number of cells. We can just take yeast cells and enter those. But you have to feed them sugar. And the way to make this really scalable, if you do the math, sugar becomes very expensive at a certain crossover point. Right now you could use sugar and produce a whole lot of stuff very cheaply, but it won't get us to where we need to go. So sunlight, despite what Nathan pointed out that goes away at night, is actually part of the biological process. And what algae cells do, the same thing we do, after you eat a meal, like most of you have just done, you convert a lot of that sugar into fat. Well, that's what algae cells do. They take the energy they get from the sun and the carbon dioxide and they make fat so they can get through the night or they can get through starvation conditions. And there's about 100 different genetic components we think we can manipulate and each. And eat natural algae cells. Well, we're in the chain of events that produces that conversion. The ultimate way to do it would be, and we're starting to do, is actually synthesize an entire eukaryotic algae genome so we can systematically make all these changes in an engineering type fashion versus random biology. The problem with existing molecular biology, people change one or two genes at a time and you'll never get there with that. I see. I mean, we need a fundamental change of how we approach all this. And now we have the technology to start to do that. Right. And so when you visualize the end state, if it succeeds, if you are able through running that genome and then starting to manufacture a synthetic algae that has this rate of productivity that would yield 10 to 20,000 gallons an acre if it were farmed, when you get, if you got that far, what would the manufacturing system be that would allow you to produce this in a realistic, sustainable, acreage available way? So in part, we just need sunlight and mostly seawater or brackish water. And the goal is not to produce an end fuel itself. I think this notion of biofuels is not a very well thought out notion. The program we have with ExxonMobil is to actually make a bio crude going from CO2 and just making these large chain fatty acids that can actually go into a refinery and make gasoline and diesel and jet A fuel. So it's not an endpoint of getting fuel, it's just getting large chain hydrocarbons, which these cells do very readily, just adding on more carbon from CO2. So we can recycle the CO2 and make it a sustainable program. This notion of doing things in these large algae arrays that people see huge pictures of, it uses, in my view, way too much water. It opens it outside contamination. It's just not going to get us where we need to go. But you don't need anything like agricultural land. I've argued, not in Michael's presence, it's probably a great use of Arizona. Having all the sunlight, they have their desert land and depending on how the things are done, I think they need to be done in a closed system. You can recycle the water. And we have some great microbial ways of recycling the water. Microbial fuel cells, we can take now at our institute in La Jolla, we can take human waste right from the sewage plant. And just by having a microbial fuel cell where the different microbes self-select on the anode and cathode, they generate electricity and they completely clarify the water within about 24 hours. No energy input, we actually get energy out of them. So we can take that, we can just recycle the water and reuse it in a closed system. So it'll be some type of a closed system. We need, obviously, facilities the size of San Francisco to produce the billions of gallons that are needed. I mean, it's not a trivial investment. So it'd be a massive industrial plant, the output of which would be bio crude, which would then be shipped to refinery. So you'd build it near a refinery, so you could just pump it in and in fact, you get all the CO2 out of the refinery because refineries are pretty heavy sources of CO2 production or a power plant or just places, you know, people keep talking about carbon sequestration like that's an answer. Trying to capture CO2 and bury it is just dumb. It's going to be the main renewable for the future. We can take all that carbon and convert it into anything we want to convert it to. NASA is thinking about this because I'm thinking about going to Mars instead of carrying everything up there. It's a 95% CO2 atmosphere. Make everything from CO2 on the spot. So everything in our body is carbon-based. All the biology is carbon-based. People have just, they're not sort of too willing to go this direction because people have tried these simplistic biology experiments in the past and they haven't worked out. Right, so thinking about this as a disruptive technology, certainly in the liquid sphere, we've described an end state where you've got very large-scale bio-crude plants next to refineries recycling carbon dioxide, recycling water, and therefore replacing, you know, some huge amount of fossil fuel liquids that we now either produce or import. That's a disruptive outcome and you've explained how you're thinking started to lead you towards visualizing that. So where are we on the engineering chain? How far along are we? Well, so keep in mind that, you know, I have this equation. I'm just going to put food equals water equals fuel. So it doesn't matter where you're going from food to energy, energy to water, to fuel, they're all interrelated. We have to solve all the things simultaneously. And if you look at the production of the corn at 18 gallons per acre per year, I mean this is a corn-based economy largely. It's probably one of the dumbest things the U.S. does. So if you're going to try and do this from corn just to replace transportation fuels in the U.S., it would take a facility three times the size of continental U.S. If you're going to try and do it with algae, it would take a facility maybe using a third of the state of Arizona. It's a pretty big difference in what could be done. But the same exact things that can be used to make these hydrocarbons for fuel can replace what we do for food. So look what's happening with the palm oil industry. One of the biggest contributors right now to CO2 in the atmosphere is clearing all this rainforest and clearing land for planting more plantations. So easily algae could get in the next decade to producing 10 times of efficiency of what oil palm does. So why not just make palm oil if that's such a great commodity? Let's just make it in a facility one tenth the size of Malaysian Indonesia. So when you say algae, you really mean synthetic algae that comes out of your innovation? Or other people using this technology. Absolutely. This is not going to come as much as I would like it to. It won't come out of one institute. We need a thousand groups using this. And that's the fundamental problem. We're not funding a thousand groups. Well, but your project is one of the most visible and I'm just trying to get a feel for how you think you're going, where are you in the discovery of whether it'll work. You mentioned sequencing the algae so that you could manipulate multiple genes instead of trying to fiddle with natural sequences. Have you actually sequenced the... Most of the 80 million genes that we have in the database are from algae cells in the ocean. So we have tremendous diversity of biology, tremendous diversity in the computational space of genes that affect all these processes. People had simplistic and therefore usually wrong notions about how to increase oil production in algae cells. And the thought was, well, you have to have photoreceptors on the surface of the cell. They capture the light. Therefore, if you have more photoreceptors, you'll capture more light and therefore make more fuel. It's just the opposite. In fact, anybody who's ever taken a sample in the ocean, out in the ocean, knows that algae cells sort of move up and down on the water column to develop the exact level they want for filtering out light to get the energy they want. Quite often, it's over 100 feet deep. So we found by just engineering the photoreceptors to make less of them, efficiency goes way up. So some of this stuff is counterintuitive of just more is better of everything. You take 100 different parameters like that, and you can engineer those by making substitutions in this synthetic cell. 20,000 may not be the limit in terms of gallons per equivalent of acre. It's hard to know what an acre is going to mean if we can go vertical, but it's sort of a useful comparison of what we do with agriculture right now. And so today in October 2011, what do you think is a realistic timeline for discovery of the potential of that kind of re-engineering of synthetic algae to start to get towards 5,000 or 10,000 potential? Well, fundamentally, the only funding we have right now for making a synthetic algae cell is our investor funding at Synthetic Genomics and funding work at the Venture Institute. The huge program we have with ExxonMobil doesn't go so far as starting with a synthetic cell. In fact, it's starting at the other end. We're doing what everybody else did of looking for naturally occurring algae to see if there's any super algae out there that might do this. That's what their investment is about? That's what the first couple of years have been about. So we sort of found what everybody else found is no, there aren't any super algae out there that do this. Edgar, are you going to be able to persuade them to back your more sort of synthetic approach? I'm hopeful, but I'm an optimist, right? I wouldn't be in science. Well, we'll take some questions in a minute, but I have to ask the question that I'm sure my cranky great-uncle would ask if you came to Thanksgiving or we had this conversation, which is, is there any danger realistic or put it this way? Why is there not any danger of manufacturing a form of algae that escapes from your closed system and sucks up all of the fresh water that we have left? Well, there is actually a, well, it would be if algae produced the equivalent of 20,000 gallons of oil per acre per year, the oceans would be a sea of lipid, not of water. It would not be a good outcome and 30 or 40% of the oxygen we breathe comes from algae, so we don't want that to happen. So it is a theoretical danger. So a key part of, and that's one of the best parts about synthetic life is we can engineer in all kinds of self-destruction safety mechanisms. Why haven't there been any accidents from the tens of millions of experiments done in labs throughout the world with laboratory E. coli putting genes from every species? It's because that E. coli has got a chemical dependency in the lab and if it gets spilled down the drain or gets outside it can't survive. So that's the simplest mechanism but we can actually build in self-destruction gene cassettes. In fact, President Obama on our announcement last year asked for his new bioethics commission to take this on as their number one issue and they issued a report last December and part of that report said there needs to be a really developed effort to build in more safety mechanisms to discover these so that that doesn't happen. So that anything that's in a facility can't survive outside of that facility. The other thing we do is we built in this notion of water marking the DNA. So this first synthetic species that's gone through billions of replications has a URL built in. It's got the names of 46 scientists, has quotations from the literature, has the names of the institutions, has a whole new code for writing the English language all built into the genome. So we can sue them if it goes wrong? What is the balance of that? No, but you can certainly track them and if this becomes part of the ethos of this new field I mean just think how could screw up the study of evolution of we just made this synthetic organism that looked like it was halfway between monkeys and man or something. So we need to carefully control this in a thoughtful fashion. It's perhaps one of the most powerful technologies that humans have ever had because you don't need the kind of teams that Nathan would need to build new nuclear reactors. This is a handful of people working in the lab that can actually use these engineering skill sets. We're actually building a robot to make a million chromosomes a day. And we're trying to build a robot that will be self-learning so it can learn biology 10,000 times faster than any scientist can because we don't know what most of these 80 million genes do right now. So the limitation is our knowledge of biology. Well so just a couple more questions before we open it up. I think we're doing all right. To this question of the investment that would be required to see this hypothesis all the way through to on the synthetic algae and the potential pathway to a disruptive bio crude or bio fuel. If I were an investor and as a non biologist I guess from what you've been saying one of my questions would be given the novelty of the synthetic cell itself having first been demonstrated at least as proof of concept in a pretty unambitious way in terms of the functionality of the cell as recently as just this year what is the evidence that a soup to nuts synthetically engineered cell could actually perform the ambitious functions that you're seeking. That's a great question. So you're trying to look at what exists in this incredible range that we find in the oceans and in algae cells. Every one of the components that we feel necessary to get to this 20,000 number exist in nature in one cell or another. Just they don't exist all together in one cell. So nothing new has to be invented. We just have to combine them in a way that nature has not done before. Think of the synthesis methods and doing the computer that it's just a new very rapid way speeding up evolution by billions of years. And then just lastly before we turn to the audience Michael introduced you with reference to your sailing and now we can see what you've been doing on your boat, studying algae as well as I guess when the fish don't come in is that what you So then it becomes apparent how your depth of thinking about this has evolved from your engagements with some of these natural genomes. But obviously you've been thinking about biology from a much wider perspective than that associated with algae and liquid fuels. Can we just step out of our conversation about disruptive transportation fuels? If you were to forecast if you came back at the end of the century and looked around at the way the world was organized. Yeah, okay. Well, you're probably as good a master of the answer to that question as any of the rest of us. If you can figure that out we'll all be with you on that too. But at the end of that century if you think about the much broader array of the energy economy including power generation and the way people live in their homes and the way industry works and the way computers are powered and so forth. Apart from the insights about biofuels are there other insights that biology you might think will ultimately provide about the way we organize our lives and our energy? If these things are taken to logical conclusion we're at the stage of totally taking over evolution in a very dramatic way. And so when you look across the board this it's hard to envision a part of humanity that would not be substantially impacted. Food and agriculture they're related to the amount of fuel and energy needed. If we can make that far more efficient like a thousand times more efficient which is what we need to do to make the fuel side economical that would have a huge impact on food. But we will start to design food in a totally different fashion. We'll change how it's produced and algae may not even be the right thing because we're taking those because they're naturally synthetic photosynthetic. Why not just design a new cell that you add the photosynthetic properties to if you really want to use sunlight or you make a heterotrophic like some algae are they can use sugar at night and sunlight during the day make a yeast cell that will do all this with 10 times the efficiency of metabolism. But we're trying to scale up protein production for food purposes and what we see happening now in the leading parts of the food industry like Nestle and Tenral Mills are trying to use what we did with the human genome. The discoveries we did with the microbiome your 200 trillion microbes that live on and in you that determine a lot of your life outcomes putting this together with these new synthetic capabilities to design foods that work specifically for humans in a far more nutritious efficient fashion than what we get by our historical consumption of things like maize. All right. Well that's an appealing thought. May not taste it. The woman there and then the gentleman next door please wait for the microphone and please if you can identify yourself. Listen Morgan Taylor-Jones Craig algae require five times as much phosphorus as land-based plants do they're five to ten acts more productive but the question will be where will you get the phosphorus because the world is starting to run short. And innovation of Lisa is a major producer of algae and working on that herself. So one of the big discoveries in the oceans was there's a totally different phosphate requirement in consumption in the Atlantic versus the Pacific Ocean. And so these cells in the Atlantic Ocean seem to thrive with a whole lot less orders of magnitude less phosphate. So there's a lot of biology that the kind of conventional terms that people use in this may not actually be true but some of these things could end up being limitations depending on how they're done. The raw materials are a key part of the future. General with the microphone. Let's talk about location Andrew Patterson by the way. Let's talk about location price and how we get this thing deployed. You mentioned two interesting concepts and one was scale and the second was capturing CO2. We've got a thousand coal plants maybe 500 of those have enough sunlight to do what you need to do. There's 500 locations probably some gas plants fit that category as well. It might be easier to take that CO2 and move the fuel than try to move the CO2. Are those 500 locations where we could build the kind of plants you're talking about? So it really depends on a few things and this is sort of where all the different sciences come together. So there's a lot of ways to concentrate sunlight in different environments and there's some pretty exciting ways to do that. People haven't used it before because it generated heat. But now we're just simple filters. You can get just the visible light coming through that the cells need to leave and bouncing back the UV and infrared. So basically you can have a closed system in any environment. It becomes what the cost of these facilities are and what's the cost of manufacturing. If it's a really cheap renewable plastic that we make these big bags in the size of this room that after you use it just recycle and make another one that's going to be pretty cheap and it can be highly distributed. Moving CO2 around is not going to be so difficult. That pipes pretty nicely. But there's no reason not to have these in different environments. Algae grow almost anywhere. Photosynthesis obviously works in a range of environments. But there's lots of ways to concentrate this on light and distribute it. In theory you could have these facilities underground. My name is Martin Appel from the Council of Scientific Society Presidents. The nexus of water, land, energy and many times force has become the source of our agricultural systems. How effectively do you think we could replace them over the next couple of decades if we were to shift into the kind of things you're thinking about can you conceive of in fact replacing a lot of our agricultural systems with real food production this way and do you have any other product ideas that would be equally high impact? So when you look at one of the worst culprits and I had a nice steak last night so I'm not casting stones anybody it's beef production. So it takes roughly 10 kilograms of grain to produce a kilogram of beef. It takes 15,000 liters of water to get one kilogram of beef and those cows produce a lot of methane at 30 times the impact of CO2. So why not get rid of the cow? You know meat is a complex of a series of proteins. We know what they all are we can synthetically make them in these same kind of systems and reconstitute. So that we're going to have a big problem with defining what a vegetarian is in the future if we don't kill animals to make meat. We grow these same things a plant producing a chicken big nuggets. But all you know if you open your mind to what this technology actually brings to the table anything is possible. I mean there's no reason to start with these existing systems that cause all this problems just eliminate them. I think Paul had a question here in front. Paul Roberts. So it sounds like you're still very early in the sort of economics sort of modeling this but what's your thought about the range of time that you're going to need to get this to the point where it competes with say $100 oil $100 barrel oil and once you're at that point how fast can this be scaled up? You talked a little bit about sort of modularity and sort of small scale but what are your sort of ranges sort of best and worst? Yes. So there's two components one is the very tiny engineering the molecular engineering we're doing on these cells that are essentially invisible to the naked eye and the other scale is the macro engineering for building giant plants to grow a whole lot of these cells. The best estimates out of the program we had with Exxon they have with Exxon is if we can get to the levels needed economically would be 10 years before you could buy gasoline made from CO2 through this process but it's not a 50 or 100 year process and if there was a lot more investment it could go a whole lot faster. So scalability should be very easy to duplicate these facilities once one works there's nothing better the nice thing about biology is we have exponential growth If we can do anything in 10 years it should start to happen in 10 years. I mean facilities have to be able to produce a billion gallons a year to be effective. So that's 10% for one facility basically. So Craig we talked a little bit earlier might be interesting to have you talk a little bit about why we don't have a thousand groups working on this kind of problem one of the barriers to that and what is it about how science and technology investment in the United States is structured that keeps these activities down to so few teams. So it's a great conversation we've been having because this has been a real issue throughout my scientific career and as Michael said in the introduction I've been at universities I've been at the NIH I've been briefly out of Solera which was a New York Stock Exchange company so I've kind of experienced the range of things. All the breakthroughs that I've made in science or my teams have made not one of them came from standard government research funding. In fact the breakthrough that's heard of all this was developing this new method for sequencing genomes in 1995 when we did the first one Ham Smith the Nobel Laureate and I wrote a grant that submitted to NIH for this new method and it was turned down with sort of extreme prejudice Francis Collins wrote this letter to say they were absolutely sure it would not work and they weren't going to fund it and it's only because we had a little bit of money in the bank that we funded it ourselves. That funding if you calculate the return on investment has been worth three quarters a billion dollars in funding to my not-for-profit institute since that time. All the work that we're doing with the first synthetic cell what we did with the human genome all this has come from private capital because the government wouldn't fund this and but what does happen as soon as we sequenced that first genome in 1995 and proved that the method worked we had so much federal funding to do a lot more genomes that it was ridiculous but you can't get funding in this country generally for breakthrough things it's you can get lots of funding to do me too things and do more once the breakthrough takes place so I think as we're talking DARPA as one of the few agencies will give you money for a high risk but the risk is the antithesis of risk capital they won't take any risk with it whatsoever and I argue that we should be as a public frustrated we don't have a hundred to a thousand times as many breakthroughs and discoveries for all the money we spend on science because very little of it goes to new things that could make a difference right so if I were the president and I or the dictator and I reorganized all of our federal funding taxpayer funding and scientific research and put you in charge of it how would you assure me and the taxpayers that your method for supporting breakthroughs would withstand audit in 20 or 30 years or should you or would your message be just forget about it trust us if the audits not for 20 to 30 years I think it's a no-brainer to do it that the trouble is our political system wants to audit this you know immediately we talked about the proxmire golden fleece awards that would ridicule government funding for things that the public didn't understand what the title meant and so I think that helped contribute to the government employees being afraid to take any risk to fund anything that's the right time for measurement if you measure it even 10 years out there's no question it would be a huge benefit yet you measure it on what's accomplished when you take all the money we put into the research budget and you measure the breakthroughs on that you know they're touting very few things that really came from all this funding so if you just even conservatively made 30 or 40 percent of it risk capital sort of like DARPA funding is where if you're not taking risk you get fired I'm certain we would have at least 10 times as many really fundamental breakthroughs and science very quickly so it's as much cultural it would be your leadership message to the people making the decisions on the front lines about what you expect of them is anything else your notion of having a dictator really helps for this kind of process and on the one last question in this string you mentioned that the capital you are occasionally able to attract to risky breakthrough projects comes from the private market I would imagine there might be a risk of market failure there in the sense that on the one hand private investors might be willing to shoot the moon because that's what private investors do but on the other hand the kinds of breakthroughs that they may even succeed in funding are often so far from commercialization that they really are performing more of a basic research than a commercial research function well that's the challenge and that's the challenge companies like synthetic genomic have of getting to things some things in the relatively short time that actually prove the concept is correct and I think the time to market with new medical foods the vaccine that you and the rest of us might get next year or the year after for flu will very likely come from our synthetic DNA process so in fact it's a place where the government is working in great cooperation with my organization and with Novartis so Bartis funding us actually to make this entire process of we now have it down to where they email us a hypothetical flu vaccine sequence of a new pandemic strain and our goal was over several years to get it under seven days for making that new vaccine ready to go into scale up production our part with the DNA synthesis now we have down to less than 24 hours and so we have the entire process down to less than seven days and at least one of those days is just the transportation of we make the virus in Rockville, Maryland we have to get the DNA fragments from the local company and then we have to get that synthesized virus up to Boston where Novartis then rescues and gets it ready to go into their new multi-billion dollar facility in North Carolina largely paid for with government money that this one facility with our new synthetic process if there's a new pandemic strain could make enough for the entire world very quickly so that's a place you know there are parts of the government that work very efficiently to funding new ideas it doesn't translate to most of the government though so flu vaccines will be the fastest thing on the market why don't we call it time and we are in fact right on time it's an honor to have you with us it was a pleasure to listen to you and so please give Dr. Bender a round of applause