• Home
• Blog
• Podcasts/RSS
• Store
• Help
• About
• Advertise
• Contact
• Pressroom
• Speaker Directory
• Partner Directory

Stewart Brand: Good evening. I’m Stewart Brand from Long Now Foundation and welcome to, I guess it’s our third or fourth sort of debate. Most of you are familiar with the introduction cards so I don’t have to say much about the speakers. On the back is where you write very legible versions of question you might have because Kevin Kelly will be up here looking at the questions and trying to read them in the dark. He’ll pass the good ones up to me and I’ll hit these guys with some of the best. I was at Stanford fifty years ago and the Biology Department, we did not have a Department of Bioengineering and it would have been unimaginable even though molecular biology was just getting cranked up at that point. This is a technology that’s growing about as fast as microbes do. That is with greater exponential speed than information technology has. We’re now at the point similar to when microcomputers began to replace the mainframes and the minicomputers; and the making of the technology left the universities and the government labs, and went into garages. So, we’re now getting garage biotechnology. And one assumes, “Well, what does that mean?” There must be some good news and some bad news and then, how do we tell the difference? Tonight, we’ll use our debate format which doesn’t have winners and losers; it has probers in both directions. Previously, we’ve asked the audience to suggest who goes first but tonight, we really need a grounding of what synthetic biology is. So, we’re going to ask Drew Endy to go first. And the format is he speaks and shows slides for fifteen minutes, then the three of us sit down up here and Jim Thomas interviews Drew to draw out more background, field data, all the stuff a good interviewer does. And to show that he’s paying attention, when he finishes that ten-minute interview, he has to summarize Drew’s argument to Drew’s satisfaction or Drew says, “That’s it. You got it!” Then they reverse roles. And Jim Thomas from the ETC group comes up and does his fifteen minutes and then sits down in is probed for ten minutes by Drew, and then Drew has to give his position up to the point that Jim agrees, “That’s right. You got it!” And then, we’re into more free form interaction, your questions, and so on. Let’s start with Drew Endy.

Drew Endy: So, my remarks will start with what I want to do; second, why I want to do it; third, what’s happening with respect to the wet technology, some of the issues that come up, a proposal, and that’ll be it. What I want to do? I’d like to develop tools that make biology easy to engineer. By biology, I mean the stuff of life, so a little bacteria that swim around, make chemicals, perhaps someday go into your body and fix stuff up. I also mean the stuff of life like this; larger objects, mammals, what have you, bring them back, change them. And then once we get all that working, maybe other things too although that might be more than ten or twenty years from now; so, spaceships that self-assemble, ecosystems, or Trey Parker’s polygluteal monkeys. In other words, how do we take this material, the one part of nature for which engineering as Stewart mentioned has not really yet been well developed and turn it into an engineerable substrate such that were it ever possible to make gigantic programmable gourds that differentiate into four bedroom, two bath houses; we could do that. These are ideas obviously, and it’s not clear that the substrate of biology is a physical material, chemical material to support all of these but one can imagine. What do I want to do? Part 2; tools that enable humanity. It seems to be irresponsible to set out to rebuild the living world if it were without also understanding who we are and what we intend to do with that capability. So, for example tools that support conversation. This is a slide of a website from Paul Rabinow's group at Berkeley trying to bring people together to talk about some of the issues of making biology easier to engineer. Tools that enable the sharing of wisdom, so if we have tens of thousands of years with biology as a tool for us as a source of food, how do we take advantage of that or at least continue to recognize and celebrate that. Tools for building a community, so if this is a photograph of students from Lincoln High School here in San Francisco working at UCSF, “I was a teenage genetic engineer last summer,” they say. Is that good or bad? And how do we give these students a future that they can build for themselves where they can take responsibility for the direct manipulation of genetic material? Tools for safety; if this is The Subway Newspaper from thirty years ago in Boston where they were publishing recipes for how to clone a toxin in your kitchen, is that a good or bad thing to do? How come people didn’t come forward doing this or did they kill themselves trying so we didn’t hear about them? Tools for security; if this is a publicly accessible sequence for a genome that happens to encode a hemorrhagic fever like Ebola and you can each download it from the internet and purchase the DNA encoding it for $20,000; do we secure a world based on biology on which that’s possible or not? Tools that enable beauty; beauty both human constructed and inspired by what we see in nature. So, those are the two things that I’m arguing for. Tools that make biology easier to engineer and tools that enable humanity. Why do I want to do this? One, to understand. You can take apart a car in order to understand a car and that gives you some sort of understanding. But then if you take the pieces as they’re scattered about your driveway and attempt to put them back together, you might have a couple pieces left over, you’ll have an “A-ha!” moment when you turn the key. It might work or it might not. Basically in biology, in its modern era over the last seventy years, we’ve inherited a reductionist approach driven by a physicist starting around 1930 and that’s became molecular biology and genetics. We’ve gotten really, really good at taking natural biological systems, pulling them apart, studying their individual components, reading out their DNA. But we don’t actually understand how all those components yet go back together. So, one of the real reasons I’d like to do this is to understand, learning by building. And just as an example of how bad we are in terms of understanding natural biological systems, I’ll show you this little movie that’s a research project that’ll published from my lab. This is a movie of bacteria E-coli growing and dividing and all the cells have been infected…excuse me, two of the cells have been infected with the virus and they’ll turn green, the two infected cells. And you’ll see one of the cells popped, the virus is so tiny you can’t see it but you can see it as it destroys the cell. And the other cell just keeps growing and dividing. This is for a virus that was first isolated from nature around the 1950s. Its genome was read out 48,502 base pairs in the 1980s. So, if you’ve heard of the company 23andMe for studying human DNA, you could head a company for this virus back in the Reagan years. We have no idea why one cell will pop and the other cell will continue to survive. We have some stories but no biophysical models. So, by learning how to put these things back together, by taking the pieces as the biologists have described them as these little entities and trying to reassemble them, we might learn that our models of how these things are actually parts, still they’re not quite parts like we think they are. Another reason I’m excited and I’m arguing for getting better at engineering biology, developing tools and support that, and tools that support humanity is to enable what I’ll call sustainable agility as well as artistry and that might not be the right word. I might mean just simply beauty. In terms of sustainable agility, you folks might have seen this before; this is a comparison of before and after corn or maize. On the left, you see corn prior to domestication. And then on the right, something that’s more familiar. If you look at the foods that we eat, we eat very few of the things that are edible as far as plants are concerned. So, one thing I might hope for the future is agility with respect to domesticating or whatever the equivalent is to different crops, both as the environment exists today and perhaps in a changing environment. Tool kit, so what are some of the technologies that exist today? Well, to put this in context, we’ve lived in a world where for the last human generation, the last thirty- five years, there’s been since the invention of recombinant DNA, the birth of the modern biotechnology industry, companies like Genentech here in the San Francisco area. And these are the tools, if you will, of genetic engineering, some of the most basic tools; recombinant DNA, lets you take two existing pieces of DNA and cut and paste them making a new molecule that might do something useful such as produce insulin in bacteria so you get that drug more reliably and serve as for treating diabetes. Polymerase chain reaction, the second old tool that you take a single molecule of DNA and make many, many copies of it so it’s more easy to do stuff. And then sequencing of DNA lets you take a molecule and then read it out, getting access to the information. These are not the only tools that can power the engineering of biology and much of what I view synthetic biology to be about is the invention and implementation of new tools. So, for example construction of DNA. Rather than manually manipulating DNA with enzymes, let me just have it constructed to order. Biology is often times very complex, maybe I can abstract it and simplify it. I’ll give you examples of four and five. And then, this turns out to be a very radical idea, maybe we could standardize biology so that the component tree can be reused more easily. Here are some specific examples. So, DNA construction. It turns out that back in 1982, a chemist working in Colorado more or less perfected at that time a chemistry called phosphoramidite chemistry and what this means is you can buy in jars chemicals today which are derived from sugar cane, and these chemicals end up being the four basis of DNA or phosphoramidites in form that can be readily assembled. So, four of these bottles up on the top here, one will be a bottle of A, T, C, and G and so one. And you hook these bottles up to a machine. Into the machine comes information from a computer, a sequence of DNA, T-A-A-T-A whatever you’d like to build, and that machine will stitch the genetic material together from scratch. So, if you’ve ever seen Star Trek where they have the food replicating system and you know, “I’d like a pumpkin-spiced mocha or latte or something…” you can compile that from warp energy drive, I don’t know exactly how it works. DNA synthesis is the equivalent technology. You take information and material, and you compile. You take information and the raw chemicals, you compile genetic material. It’s practically speaking, the coolest, most impressive/scary technology I’ve encountered. DNA is complicated. So, if we were to do all our genetic engineering at this level of resolution, T-A-A-T-A-C-G-A-C-T-C-A-C-T-A-T-A-G-G-A-G-A, it would become tedious, if not unreliable, it would be akin perhaps. The analogy is not perfect, perhaps like programming a computer in machine language. At some point, it might be good to know how to do that but often times, people would like to program at a higher level. And so, some of these ideas like obstruction of genetic componentry involves the idea of taking these different layers or function, the DNA layer and putting on top of that a parts layer, we could call genetic objects that just do something and you don’t have to know all of the sequence information, and then we might be able to build still higher level functional objects like a device that could receive or send information or smell like bananas or make a balloon, and then maybe we could have a system; makes a drug, swims around, finds a tumor, and attacks it, who knows? If we could pull this off, what we’d end up with is a future in which some people could become expert systems engineers in biology that could start to design and build organisms. And they wouldn’t actually need to know down at the bottom that DNA was made up of four bases. Let alone anything about phosphoramidite chemistry. They would compile down via tools to the sequence level, ship that information over, somebody would print the DNA to get their DNA program back, and then run it. It turns out we’re working on this. There’s a registry of standard biological parts at this website. Today, you can get thirty-five hundred BioBrick DNA parts. They’re freely available if you work in a research university, and simply because the legal system requires we distribute these parts under what’s known as the research exemption. This collection of parts is growing geometrically. So, two months ago, it was 2,000 parts. We just had students come in with 1,500 more. Students do things like these; showing up in the lab dissatisfied with the bouquet of E-coli, how it smells; they decide to reprogram its stench. If the cell is growing, it smells like winter green; otherwise, print banana smell. You could find the part that they made J45-200, there’s a DNA sequence. When you put that sequence of DNA into the bacteria, it smells like bananas. They were sufficiently accomplished as teenagers, first and second year undergraduates but they went live after a couple months with a smell-test demo. Now, along with these set of tools like parts and standardization, we’re seeing if I come back to the construction business of DNA also a geometric increase in the pace or capability of DNA synthesis, says the paper published within the last year where folks are building from these raw chemicals, from scratch a piece of DNA almost 600,000 base pairs long; the length of a small bacterial genome. In fact, the biggest projects I’ve seen today have assembled pieces of DNA that are almost ten million base pairs long, almost the size of the genome of baker’s yeast. Limits; there’s going to be some interesting limits. One, to look ahead to Saul Griffith’s talk from January, probably comes from energy. Saul, here is very concerned about human civilization and where we produce our energy, and whether or not we’ll be able to transition to something that’s sustainable and renewable. It turns out that biology has a thing on our planet. It doesn’t have access to that much energy. He estimates it might be half a terawatt out of a civilization, our civilization that’s running on 15 or 18 terawatts. Maybe he’s wrong by a factor of ten, and biology really can get access to five terawatts. It’s still not going to be an excess of energy via biology. So, if you hear about bio-fuels right now, bio-fuels won’t solve our entire energy problem. And because there’s a limitation there, it’s going to put tremendous pressure as I hope we hear about on our land use and so on. Security as I alluded to via the Ebola sequence on the screen is a huge issue. And since the anthrax attacks on our country back in 2001, we’ve spent over $60 billion in the name of biosecurity. This has largely resulted in a reestablishment of classified biosafety level 4 facilities. BL4 facilities are facilities working on the most dangerous pathogens. Ironically, the FBI claimed to have traced the anthrax attacks back to the very facility as shown here. Then, we again come back to the issues of communities and can our generation going forward and beyond bring together what might seem like polar opposites? On the left, you see the IGEM community. This is the Genetic Engineering Olympic students doubling in number practically every year. On the right, are people who are dissatisfied or actively against the deployment of genetic engineering. I have some proposals to consider and I’ll quickly show them here. Should teenagers practice genetic engineering? Yes. Should military force include biotech? No. Will biohackers be good or bad? They’ll be good if we encourage them and celebrate them. Should the parts be patented or shared? They should be free but maybe we have some interesting terms and conditions to discuss. And should genetic engineer sign their work? Yes. Last slide, I’m arguing for the development of tools that make biology easy to engineer. In parallel, I’m arguing that we also develop tools that enable our humanity as we take biotechnology forward. Thanks very much!

Stewart Brand: Outstanding! Alright, so everybody’s light’s working?

Jim Thomas: Thank you very much, Drew. Thank you everyone for coming out on a Monday evening. We really appreciate it. And as always it’s great to hear a very reflective technologist and may there many more like him. You began your list of questions at the end there and I’ll start by saying, should teenagers practice genetic engineering? You think they should. Who should and shouldn’t. Who else? If there was a limit, who should use these tools? What would that be?

Drew Endy: I think so long as somebody is disposed to be constructive, right, and I might even go further than that and say, so long as somebody is not disposed to be destructive, that would be the initial set. Then, I’d open that up for wiser consideration but I don’t know that I would want to preclude access to these technologies. It seems my gut tells me that many of the technologies around biology have been not officially locked up but hard to get access to, and I think it’s ironic that some of the difficulty in getting access to the technology comes out of the conversations of three decades ago where issues of safety drove a very, very strong institutional oversight framework to come into existence. Many of those safety concerns were well founded. But as the cost associated with that, we now live in a world where most people don’t feel comfortable talking about DNA or genetic engineering. Most people presume that all of the work is dangerous and that’s what we inherit. If I look forward, there are much more serious dangers I’d get freaked out about with respect to a future where a small number of people have access to matter compilers for genetic material. Imagine if only one or two organizations in the world have access to that technology. It’s much more exciting for me to imagine a world where anybody who might usefully deploy biotechnology for a local situation has access to the tools, has access to the know-how, and can do it. Now, that might be a fantasy for many numbers of perspectives but that’s my starting response.

Jim Thomas: And specifically then, you go on to say that your concern, if I got this right, that the military has access to this technology, and what would you do about that?

Drew Endy: Matt Meselson from Cambridge, Massachusetts, a generation before was part of a group who argued successfully that the military, the US government should stand down its offensive biological weapons program. As I understand it, having inherited literally, not being alive at the time that world. And so, the arguments as I remember having learned them that they made were, geez, we already have weapons; two, we can’t really control biological weapons; and three, other people can develop them and there’s not limited access to say, nuclear material with biology. Biology is everywhere, so we can’t sort of lock up the raw materials. So, they have no strategic value for us. And those rational, reasoned arguments carry the day during the Nixon administration. I wonder to what extent we’re seeing today perhaps are relaxing on some of those reasons, maybe we’re getting better at controlling biology. And so, we’d want to be vigilant if you will, to pay attention to the debasement of any of those reasons. But another thing, at least in the United States, there’s been a very, very strong immune response around biosecurity from the anthrax attacks in the fall of ’01. So, I’d like to just at least hold the line around some of Meselson’s arguments. Go back and read Scientific American from that point in time, you’ll see, “Hey, we should not have classified biosafety level 4 facilities. Let’s do this in the open if we’re going to do anything.”

Jim Thomas: So, a lot of the argumentation for developing, for example the 1918 flu virus was synthesized a few years ago using synthetic biology. That’s a virus that called 50 million people in the last century.

Drew Endy: Yeah.

Jim Thomas: And the argumentation was that it was in order to defend against pandemics, the flu that is still to come. Do you accept that? If that’s non-military or would you consider that military?

Drew Endy: That work was done at the CDC. It was done in public. There was debate within the research community as to whether or not the sequence information for that 1918 flu should be made public. Not all the researchers agreed. It was made public. It was reviewed by the National Science Advisory Board for Biosecurity before it was published. The scientific community rallied behind that. The arguments basically being made were of the form no disease has been cured in secret, and we have to keep this stuff in the open. Others, notable around this part of the world, Bill Joy and Ray Kurzweil had a nice editorial in The New York Times saying this is the most irresponsible thing they’ve encountered. I think the scientific community would point to the subsequent work and say, it was good to have that information out there, we’ve understood a little bit more about the evolution of the flu, and it’s not something that should be done without concern for safety issues but it was the right thing to do.

Jim Thomas: You talked about agility, you talked about understanding nature. I mean, another reason that you appear to be involved with synthetic biology is that you’re actually a founder on the board of commercial company using synthetic biology. What’s the role of commerce in understanding nature and building agility?

Drew Endy: That’s a great question. I was attracted to being involved with the company because one of the core technologies of synthetic biology, DNA synthesis has little or no public support. And so, if you wanted to get better at that technology, when the commercial sector, the investment sources came up and said, “We’re willing to help with this,” that was an eye-opener for me. I’ve seen the strengths and weaknesses of what you can do in a commercial sector. It’s surprising to me that there is not public recognition of the importance of DNA synthesis technology and how the public probably wants to consider having an active voice and seeing this technology develop, to have a say, and how it’s deployed.

Jim Thomas: And I was really taken by one of your last slides later on when you're talking about agility and creating agility. What you showed was teosinte, the original ancestor of maize and then you show us the maize plant. We'll, there's a plant that was developed through our consoles means without genetic engineering, and so that seems to be an argument for agility without biotech, isn’t it?

Drew Endy: Well, I'd argue that maze is a biotechnology. It's a biotechnology developed by particular methods over a particular period of time. By agility I mean, to the extent that is possible, and I'm perfectly happy to recognize what’s research and what’s ready to be commercialized to the extent that is possible if we needed that to do that faster not waiting for many, many, many generations. I'd like to have that capability.

Jim Thomas: You're very closely identified with open-source biotechnology trying to make sure that as this move ahead, it shed. But there have been people on this stage I think who are pushing for patents in this area, how do you defend against that?

Drew Endy: How do you defend against patents? I'd rather avoid that question and answer a related question just to be honest which is how do you develop an open technology platform. And you develop an open technology platform, so far as I can figure it, by doing two things. One, you build a community; and two, you protect against encumbrance of reuse and combination meaning; when you take any two things and give them away, somebody else could take these two things, put them together and say, oh this is mine. So how do you do those two things? In biotechnology, patents are the dominant form of protecting against encumbrance of reusing combination. We can't afford it with another fifteen hundred parts coming in to the collection that’s $30 million in patent fees; and if you were to give thirty million bucks, I'd go make more parts. And practically then, what that means is, we have to build a community that grows faster and can now innovate (indiscernible) who inevitably come around the periphery. There are some other things we can do. We can talk about that more in detail. So, I'm not for or against patents, but I think patents per se have a cost associated them and they have a time constant associated with them. They have a lag, and that makes them exclusive. And so, I think a lot of the innovation and pacing of innovation in biotech and the good that can come from it would be better realized by having complimentary frameworks that might operate on shorter time scales or have lower transaction cost.

Jim Thomas: So patents have a cost, but those have a very clear opportunity which is why people take them out. A number of the parts in the BioBricks are actually patented. So, this situation, this is just going to get subversive.

Drew Endy: Most pieces of DNA on the planet have not been patented. The uses of fragments of DNA, there a great number of patents in United States and in Japan and fewer elsewhere, so with respect to the BioBricks collection; our challenge right now is to take something which is openly distributed within a research community. So, researchers at universities can use stuff under what’s called the research exemption. How do we make that accessible to people within the commercial space or outside the research community. So we're doing okay now, but we need to basically extend our community and figure out how to do that. So, we're working on an agreement with lawyers and hope to have that ready for public comment. But it is a tricky problem for us.

Stewart Brand: Great. Time up ahead.

Jim Thomas: So, what I heard very clearly, you said a number of times were, you're interested in making biology easier to engineer. And it sounds like you don’t really want to put any limits on who uses it, who can engineer it. You want them to be a generally available platform, and you want to supplement that with tools that would allow humanity to behave more wisely or something like that; tools for humanity I think it’s how you put it. And your reasons for this, is by rebuilding nature from this fundamental place that you want to understand how nature works better, it's building by understanding. And you have an argument around where you called agility, that having more technological tools in our toolbox means that we can deal with some of the pressures that are coming down the pike whether that’s climate change or hunger in the case of food. And then, you talked about some of the limits that you do see on this field and some of the challenges. And those challenges included that we have limits on energy use. But neither of this is probably isn’t the appropriate way to go about in answering energy concerns with biofuels. But your concern is certainly about the military use of this technology, and you had other questions about should teenagers use this and equally shared in. And you had some concerns about the intellectual property framework, and you feel it should be as free and open as possible. Is that kind of everything?

Stewart Brand: What did he leave out?

Drew Endy: That’s 93% correct! That’s terrific, actually. I would not like to enable people who actively seek to cause harm with the technology. So whether it’s a nation, call up the military of the nation; whether it's an organization; or an individual criminal, not a hacker but a criminal. I guess, I would emphasize just complimenting what you said that it's very hard to look ahead on some of this technology given the geometric increase in some of the capabilities. So sequencing and synthesis both, but synthesis in particular has a technology. It's getting better year after year after year, much like computers are if you're familiar with Moore's Law. And so, little bits of uncertainty projecting along those exponentials lead to interesting futures. But I think no matter what, things are likely to happen pretty quickly, so maybe just to compliment what you said at the…

Jim Thomas: About the speed.

Drew Endy: Yeah.

Jim Thomas: Great.

Drew Endy: Thank you.

Stewart Brand: Jim, you're on. Great! Thank you!

Drew Endy: Thanks, Jim.

Jim Thomas: Thank you, Drew and to Stewart. My colleague, Pat Mooney, who’s lived a much longer now than I have, reckons that it takes roughly a human generation to understand the impacts of our technology, and I think he’s probably being a bit short on that. I think it's something more like a human lifetime. So, I'm not really expecting to get a very clear reading on synthetic biology tonight or anytime soon. But I’m going to argue that that lag between deploying our technologies and understanding our technologies is a good reason why we should be supplementing the art of the long view with that policy of the long path by which I mean the deliberate careful part of precaution. And I know I made that I've been build as an historian tonight, and that’s a big shoes to fill in especially if I bumped off my history degree doing direct action. But I'm going to try and not disappoint to bring at least a few lessons from history, and particularly lessons from the closest parallel that I can find which is the synthetic chemical industry. And apart from the name and the fact that DNA synthesis is a chemistry technique, what this two fields share is that both of our building synthesizing nature from standard molecular parts. And indeed the early chemists believed that they could understand nature better by building it just as Drew does. But I think the parallel that we're looking at right now with Synthetic Biology is the mid-19th century when the synthetic chemists begun to commercialize that field. I just want to quickly show you how parallel these two moments are. So if you got it 1856, this was the time when a teenager in East London called William Henry Perkin, who was supposed to be synthesizing an antimalarial drug quinine, ended up synthesizing a synthetic dye mauveine. And realizing this was a red-hot commercial prospect, he commercialized it. And a bunch of French, German and Swiss entrepreneurs, in sort of mid-19th century equivalent of Craig Venter or Vinod Khosla copied his business model, and they also started producing synthetic dyes. And on the back of the synthetic dye industry, the modern chemical industry was born. When you zip forward a hundred and fifty years and just across the bay, Jay Keasling is also trying to synthesize an antimalarial compound this time Artemisinin using biology. And he finds out that he can synthesize gasoline, he sets up a biofuels business and people like Vinod Khosla and Craig Venter copied the idea; and before you know it, you have a booming synthetic life industry. And what’s interesting is that this new synthetic life industry is following some of the same questions that the synthetic chemists faced a hundred and fifty years ago. So Drew dealing with questions about monopoly, and I hope you don’t mind, but I think they're very 19th century view of monopoly that you have. In the middle of the 19th century, you had a booming open-source movement and a rolled back of the patent movement of the patent laws. But they're really allowed the industry to take off. Within a very short time however, that itself have been rolled back. In the mid-1970s, a bunch of German companies lobbied for a strong patent law. They used that to build a very strong monopoly which by 1925 was I.G. Farben, the fourth largest monopoly in the world. And since that time, the chemical industry has been a highly-concentrated and highly-powerful industry right through to now. And if you look at BASF, which is one of those original companies, it's now the largest chemical company. It's also got a one-half billion dollar agreement with Monsanto in GMO seeds; position itself with the head of the pact on nanotechnologies. We're moved in that case, from monopoly to oligopoly. And I think we're going to see this, exactly this was synthetic biology. And while there's an attempt to build the commons we're already seeing patents being placed, being written by people like Craig Venter and DuPont which are being set to crowd out the commons and established a monopoly position. There is going to be Microsoft for synthetic biology. I salute the attempts to kick against that, but I think history is on the side of Craig Venter on this one. And Drew is concerned about militarization and rightly so. And you go back to the history of synthetic chemistry back in the 1850s. You have people like Lyon Playfair, a British chemist, saying that you could use chemistry in the Crimean warfare for chemical weapons. This caused a real stir, if we had at least two treaties trying to ban chemical weapons. But by the time the First World War came around, both the Allies and the Germans are really seeing synthetic chlorine into the wind to try and gas their opponents. Two decades later, I.G. Farben, BASF again, was supplying Zyklon B into the gas chambers at Auschwitz. It is said to the founders of BASF in the 1860s, that their facilities would be used to carry out mass murder by their own government; they would have said that was an extreme and improbable thing. But the balance of probability changed very quickly across one human lifetime. And I really do think that it's a mistake to think that with synthetic biology where we already have had agents built that can kill 50 million people as it did last century in the case of 1918 flu virus that you can, on the one hand, restrain the hostile uses of this technology; and on the other hand have a booming industry. And that really is a fairytale that the high-tech companies and high-tech industries tell their population to try and make them sleep better at night. I think if Drew is serious about disarming the future, he has to realize that the existence of an industry, an industrial capacity means that that they will be commandeered in wartime by states. Even states that you think you trust. And the way to disarm the future is to disarm the large-scale commercial production of anything using synthetic biology. And I think thirdly, looking back to the chemical industry, there's a clear lesson on economic destruction. It didn’t have to wait for soldiers to be killed on the battlefield before they're already economic deaths on the agricultural fields of Turkey, of Mexico, and of India. But in fact, those who grew the natural dyes, the dyestuffs industry, saw the emergence of the synthetic dyestuffs industry back in the 1860s as an attack on first their livelihoods and later their lives. So 1897, BASF and Bayer had a synthetic indigo dye, blue, which led to the collapse of indigo growing in Bengal. Seventy-five percent of the area planted to indigo collapsed within a decade, and then when famine came along, millions of unemployed growers ended up dead. And those are just sort of first canaries in the coal mine we've seen wave after wave of synthetic products made by chemistry putting out of work rubber tappers and cotton producers and so forth. But I think synthetic biology is probably going to outdo all of that. I mentioned already Jay Keasling, which is one of Drew’s colleagues. He has a project to working with some of the Sanofi-Aventis to replace Artemisia which is usually grown by thousands of small farmers in East Africa and Southeast Asia. And basically, to under cut them and put them out of business. But it gets further; when I spoke with Jay Keasling recently, he told me that as far as he was concerned, Synthetic Biology meant that ‘anything that can be made from a plant can now be made by a microbe in a vat.’ Think about that. “Anything that can be made from a plant can now be made by a microbe in a vat,” a statement like that if it's true, is the death knell for economies that depend on plant-derived commodities; whether that’s tropical oils or fibers or rubber or plant extracts to pharmaceuticals and flavorings and so forth. What Jay Keasling’s statement means is that, for the customers of those commodity-dependent countries which is usually the poorest countries in the world, they can now dangle the carrots on their concern of synthetic biology and then renegotiate costs. They can renegotiate trade deals. They can switch to microbial synthesis and leave whole nations up in the air, essentially to let them spiral into hunger, violence, and unrest. So, monopoly, militarization, massive economic destruction; three things that we can already see from the beginning of this in the last synthetic industry, but the real doozy with synthetic chemistry, came a full century later. And that’s in 1962 when Rachel Carson published “Silent Spring” and drew back the curtain on a host of unexpected toxicities of what was thought to be the good side of synthetic chemistry. The pesticides, the paints, the fertilizers, the refrigerants, and so forth; the whole better living through chemistry package. And for showing that tremendous cost that those benefits were paid for, she was called emotional, unscientific, she was called a fear monger, all sort of labels that today get put on people who are critical of biotechnology. But she really didn’t even have a part of it. Some years after Rachel Carson’s death, Drew and I are now part of a generation with the lowest sperm counts in history, under a depleted ozone layer, and every night my wife feeds my child breast milk with persistent organic pollutants in it. And we are the privileged ones. For communities of color and poor communities in the shadow of chemical facilities, the attack for the synthetic chemical industry on their lives and their health is something more like a slow genocide, which is not to say synthetic biology is going to be toxic, but it is to say we need to properly weigh that which we do not know. And we need to take it extremely serious. That’s being discussed on this stage before; it's the Black Swan that Nassim Taleb talks about or Paul Saffo's cone of uncertainty. In the case of Synthetic Biology, we already have significant questions over some of the assumptions underlying the notion that DNA is a code that can be programmed and is heritable and so forth. But if you have those questions we shouldn’t be moving into commercial use. And that’s why civil society generally calls for a very strong use of the precautionary principles in this and maybe we can discuss that more. I want to end with three mistakes that I see looming in the longer term for synthetic biology to open up questions. First, the discussion so far is just about microbes and we’re soon going to see synthesis of plants, of animals, and certainly of human beings and we should think what that means. Secondly, we absolutely mustn’t try and treat synthetic biology with the same set of regulatory and governance tools that we use for genetically modified organism. They are different quantitatively and qualitatively. Qualitatively, you’re not talking about a small piece of DNA taken from somewhere in nature and then put in to a genome that mostly already had existed in nature. To try to understand the bio safety of that, countries use something called substantial equivalence that is kind of pseudoscientific biosafety tool. It doesn’t work with genome, absolutely won’t work with synthetic biology where you’re going to be designing entirely novel sequence of DNA and increasingly putting it into a entirely novel genome so we don’t yet have any models, predictive models, for working out the bio safety of these synthetic organisms. And I think that’s going to be a black hole into which this, the whole field is going to get sucked. Quantitatively, it’s different too. If Drew is successful in making biology easier to engineer such as anybody, teenagers or whatever can do this, we’re going to see a massive increase in the number of engineered organisms entering the biosphere. I discovered that there’s an amazing job that somebody has here in the Bay Area which is from NASA and that’s the Planetary Protection Officer. It's got to be the coolest job there is and apparently her job is to make sure that no alien life forms get into the biosphere but I think she is looking at the wrong place. I think she should be checking out the synthetic biology labs and particularly the synthetic labs of J. Craig Venter who claims in his patents and his public pronouncement that he has a method of making millions of new species everyday. Think that up, millions of new species everyday. I mean, what does that mean? It means probably that Kevin Kelly’s all species directory is going to go find a whole lot of storage and it means that the taxonomists aren’t going to sleep for the next hundred years but what does that mean for the biosphere which is already under stress from climate change and chemicals and so forth. We know the alien species introduce to the biosphere or in to different parts of the biosphere are the second worst cause of species extinction. Which finally brings me to the third and I think the biggest mistake that this field is committing and that is that it’s adapting an extremely destructive business plan. Actually, Drew has touched on this. So far, as far as I can see, the synthetic biology business plan is making microbe to turn sugar in to something, usually biofuels or maybe chemicals. And this is often expressed as the so called the bioeconomy which is going to replace petroleum with sugar. Whether it is food sugars such as corn or cane but we know that’s a bad idea from ethanol. That if you use food sugars, you’re going to be displacing food and that pushes up prices and pushes people into hunger or more if the suggestion is long term, it’s going to be cellulose. That’s to say the woody part of our plants and I think accessing that woody part of our plants is a very dangerous move. We’re going to see a massive corporate grab on plant biomass in the coming years facilitated by synthetic biology and Drew has told you how significant that is. So here’s the difference between Drew and I, we actually share a lot of values and we do talk from time to time but Drew basically advocates for the fastest possible diffusion of the synthetic biology tools and I basically favor of a deliberate containment policy. To offer a basket of mix metaphors, I think we should be slamming on the breaks, certainly on commercialization, that we should be locking this up in the lab until we really understand it; that we should be divorcing the science from the commercial world, that’s a disaster; and that we should be very carefully looking before we leap. I mean, if we are doing all of these things right now because of the very powerful, commercial synthetic life industry is coming into being right now and that window for polite debates like this is rapidly closing. Thank you.

Stewart Brand: Great.

Drew Endy: Thank you. Well, that’s terrific. Many questions, to start, I’m not sure if this is the right question so it's, as a preface, the first one, is there some way you think practically to protect nature? So you talk about the use of these tools by commercial agents to get access to the remaining three quarters of the biomass that is not a commodity if you will. Is there some practical way from your perspective to protect what’s still not a commodity and is it only linked to decoupling the technology development from the industry and commercialization?

Jim Thomas: Well, that’s part of it. I mean I think it is as you say 24% of plant biomass is currently used by civilization that leaves about 76% or so ready to be commercialized once we have a way of commercializing it and commodifying it. And so a very straightforward way is just not to develop those tools, not develop the tools that turn cellulose into usable sugar to make plastics and biofuels, that stays with the technologists, for the world governments to enact very strong treaties. We have the Convention on Biological Diversity which exists for the sustainable use and conservation of biodiversity. That’s the place that should be making a very clear statement. I think the key point here is that those synthetic biologist and others who say that we have this available cellulose whether it is a leftover corn stalks or it’s wood in forests gives a sense, and it’s a lie, that this is somehow available. The corn stalks that are left behind the field are exactly what you need to build the soil so that you can grow the food for the next generation. That’s not available at all. It’s not available and it shouldn’t be made available. And to steal it is to destroy the soil and if we destroy the soil as Franklin Roosevelt says “The nation that destroys the soil destroy itself.” He’s absolutely right. In the forest, the idea here is that forests are somehow storehouses of carbon and sugar that we can just access when we want. It's not true their vast, vast ecosystem that clean our water and clean our air, and we need to absolutely protect and defend those.

Drew Endy: And the means for doing that are at the level of the tools development and their commercialization?

Jim Thomas: If you want to create social change, there are two things. One is that you have to have social organizing and that’s legal and political organizing and social organizing. The other is you need to prevent encroaching threats and what I see is developing synthetic biology are encroaching threats, threats to the cellulose locked up in all those forest and I want to disable those threats.

Drew Endy: You mentioned that Jay Keasling’s project on the East Bay involved taking a microbe in a vat and making Artemisinin for treating malaria. Is it ever okay to make something in a vat filled with microbes and how would you decided if it’s okay?

Jim Thomas: Yeah. Beer is a great thing to make in a vat and if that I believe Amyris started by making beer and I think should have stopped at that point, with that recent plant over Emeryville. I think the question here is and it’s a general question for technology, if you’re going to develop a technology that impacts people on the other side of the world, they have to have a say in the development of that technology. What this means is we need to have much more reflective and participative method of assessing our technologies very, very early on so we can identify who’s going to be impacted and we can bring them into the discussion. The problem is the justice problem that Amyris Biotechnology and whoever invested in them is about to make a killing, maybe literally, offer something that’s going to undercut the livelihood of thousands of people in East Africa and we need a process. And this is a bigger technology question. We need a process by which that can be flagged up and there can be some sort of intervention.

Drew Endy: Given that work that was sponsored by the Gates Foundation, do you find that surprising or ironic?

Jim Thomas: Yeah. It’s not entirely surprising but the large monopoly that tries to move in to the area of development also ends up replicating its problems in the area of development but I think it’s definitely worrying. My understanding from talking with Jay was that they were actually told that they should move on to make another business and so that’s what made them to move in to biofuels which is the second problem. We have lack of governance over large and powerful foundations as well. And we need to control that.

Drew Endy: Some of the modern computers where first built by von Neumann and his team in the 1950s. Those were commissioned to design hydrogen bombs and so on. And today, we live in a world where going through transition about a generation ago. People got basically fed up with limited access to computers and started making their own. Do you see any possible path around a biotechnology that might not be in to militarization even if nation states go bad or rogue or what have you?

Jim Thomas: Yeah.

Drew Endy: Or is that really inevitable?

Jim Thomas: I think it’s a technology which a state can use for its own interest or a powerful entity whether it’s a corporation or whatever can use. There’s a pretty good chance that it’s going to get use so I’m reasonable pessimistic I think. If this technology is going to be developed in a way that is very deliberate then that deliberateness has to try and reduce the ability for it to get into the hands of overly powerful players. We live in an unjust world. And if we’re introducing a powerful technology into unjust world we’re going to probably exacerbate that injustice unless we’re very, very deliberate in trying to attack that injustice. I don’t see that happening now. I don’t see that happening and I’m not quite sure how it would happen.

Drew Endy: If you could draft part of the BioBrick public license, is there a term or a clause or a condition beyond just you’re free to use it, that you’d like to see hard coded in there?

Jim Thomas: Yeah. Plenty.

Drew Endy: What would be your top three?

Jim Thomas: My top three, I would put two lines that shouldn’t be cross and if they are crossed, they have a further one. The first line is that there should be no release into the biosphere if anything produced using these parts and that would keep it locked up in the lab. And if it ends up release into the biosphere, there needs to be a legal mechanism to come back on that.

Drew Endy: That needs to be a crime?

Jim Thomas: Civil law maybe. The ability to try and get some sort of liability. And the second would be that these parts shouldn’t be commercialized. This is truly for understanding how nature works which I think is a genuinely good reason to do synthetic biology. There’s no need to release into the biosphere as a sort of uncontrolled experiment. So that would be a second one. And I think there’s a question if there is an overwhelming need, maybe. This has come to your question earlier if there’s an overwhelming need to cross one of those lines to release into the environment to commercialize this technology. Then it needs to be a very transparent and participative process for assessing the technology where communities beyond the synthetic biologists particularly in marginalized communities will be affected, get to have a over say whether if this moves ahead. I'm not ruling out there might be some use somewhere in the future which everybody agrees to but I think has to be done deliberately and with vigilance.

Drew Endy: Do you think there’s any role for civil society organizations to play in the development of the technologies so that they can better constrain or guide their deployment or lack thereof?

Jim Thomas: Yeah. Civil society organizations tend to…it’s a wide basket of groups but they network across many different communities and can bring different types of knowledge to assessing things over these. And I think it is a very powerful role for, not just civil communities and social movements but also the indigenous peoples communities and other groups to bring perspectives and knowledge on which technologies we feel more comfortable with and to have some kind of participative assessment, so in the role of assessment certainly.

Drew Endy: One last question, a lot of times as technologies have been developed and it becomes easier to make stuff you can see an increase in diversity could you foresee a future where humans by their ability to make or change living organisms contribute to biological diversity in a way that’s constructive or could be celebrated?

Jim Thomas: We brought Drew to the Convention on Biological Diversity and I think part of your argument there was we’ll make biological diversity. Isn’t it a great idea? I think I find that unlikely that the experiences are mentioned of introducing new species in to an environment is usually that they reduced biological diversity and my worry is that’s what’s going to happen. I’m not only person to say this. Freeman Dyson has written a really interesting essay in which he suggested that if we stop producing large quantities of new engineered organisms by amateurs, we’re probably going to lose a lot of the species that we already have. He seems fine with that. I’m pretty uncomfortable with it.

Drew Endy: Okay. Thank you very much. To summarize, Jim notes that there is a lag to the understanding that humans sort of consequences of developing new technologies and you mentioned that Pat Mooney said it might be a human generation thirty years or so but you actually thought it was longer, seventy years or hundred years. And so from that opening, you submitted for our consideration and argued that the policy of the long path leading to a precaution in considering and bringing forward new technologies as paramount, you use synthetic chemistry as a parallel and highlighted many different aspects that seemed to be parallel perhaps with synthetic biology. Noting for example the work of Perkin in 1856, developing a dye in England and then seeing that readily and rapidly commercialized by the French and others in this rapid industrialization, perhaps at that time, if I understood correctly, coupled to open patent frameworks but then that was sort of subject to the tides of the time or the decades and rolled back at various points leading eventually but also somewhat quickly to what you called a concentration of power. This concentration of power that leads to misapplication, many horrible things that we’re aware of with chemicals being misapplied back in World War I and World War II and even more recently. The economic impact of the development of chemicals also with synthetic biology and chemicals produced via biology often times contributes to disfranchisement and impoverishment of people who are not represented in the process of the development or the commercialization of the technology. Further along in the development of synthetic chemistry, you noted Rachel Carson’s experience and the generation leading up to that and what we inherit around the impact of synthetic chemicals on the environment, on humans. Drawling back the curtain on basically uncontrolled experiments, I think you might have noted that biology is at least serious as chemistry might have been if for no other reasons that the things that we’re constructing can reproduce themselves. Whereas often times chemicals, they get paid once and hopefully they get diluted or destroyed. So in summary around this part of remarks, you came back to again the idea of precaution as a principle in the development of this new technology. You noted that the conversation seems quite likely to move beyond microbes quickly. So if it’s microbes today, it’s plant tomorrow and technically I would agree with that. You thought that this was not like genetic engineering. It might be an outgrowth of genetic engineering from the tools perspective but in terms of the regulatory framework at a whole different beast and that new approaches are needed. If for example you’re compiling an entire organism from scratch and there’s nothing to compare it to, then what do we compare it to, how do we know if it’s safe, does that challenge our biosafety framework in some way. You noted that there might likely be a massive increase of organisms release into the biosphere and if most new things coming in to biosphere if anything successful takes over, it’s likely to have a traumatic effect on the rest of things and lead to a loss of diversity. In particular, you noted a problem, a mistake of vulnerability associated with further modification sugar, sugar plus cellulose, and how this provides access to all of natural living world in a way that just simply hasn’t been true before, that this could lead to further concentration of power. Drawing on some remarks, I remember from Hong Kong increases in landless peasants in Brazil for example and so forth. So to summarize, you concluded by arguing for slamming on the breaks, that we lock the technology of synthetic biology into the laboratories. We decouple the industrialization, the commercialization of the technology from the laboratory work and that we go forward with care, great care.

Jim Thomas: One more thing, I did note that the notion that you could develop a viable commercial industry and not expected to be militarized is a fairy tale and I think that’s important, that states will press commercial industry into war time use. And I think that should be in mind. Otherwise, yeah, you got it. Thank you.

Stewart Brand: Great. Thank you guys. Well done!