Systems of Life Impact Business and Society

Systems of Life Impact Business and Society

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Systems of Life Impact Business and Society

Exploration, experimentation, and innovation. All fabulous pursuits in their own rights, but what about real-world application? From food to fuel, what are people doing with all these new bio discoveries? In this video, David Kirkpatrick moderates a discussion with Stewart Brand of The Long Now Foundation, Jim Flatt of Genovia Bio and Synthetic Genomics, Inc., Steve Levine of Dassault Systèmes, and Floyd Romesberg of The Scripps Research Institute.
Kirkpatrick: So I want to bring the panel up. We’re now going to pick up on a lot of the threads that Nancy has just sort of put into the fabric and continue the discussion of big picture here—what it all means, where it’s all going, what some of the big new opportunities are going to be.
An extraordinary group of people up here. I’ll quickly introduce them and then I’m going to talk to them in a variety of ways here. But starting here, Floyd Romesberg has been in the news a lot. He recently created a new kind of life that could never have existed on the planet before by adding what he called X and Y element to the language of DNA and got an E. coli cell to reproduce. So that’s a pretty big deal, and I’m going to ask him a little bit of what that means in a second. He’s at the Scripps Institute in San Diego.
Next, Stewart Brand, who, as I said, is sort of a spiritual father for us at Techonomy, of many things, but certainly he’s got a lot to say about a lot of things we’ve been talking about today. And you heard, he’s very involved in the Revive & Restore effort, but also the Long Now Foundation, and has been thinking a lot about biotech as a transformative force in society.
Then Jim Flatt is the president of Genovia Bio, which is one of the divisions of a company called Synthetic Genomics. He is in the commercialization side, where they’re taking bioprocesses and applying them to the production of fuel, food, chemicals and other things, and he’ll tell us how that works a little bit more in a minute.
And finally, Steve Levine of Dassault Systèmes is the director of Simulia, which is a simulation product that really allows for the more rapid development of biological compounds and products, and I want to hear in detail how that’s going to apply.
So basically, what we want to talk about is the big picture. But I want to start with Floyd and ask you a few questions about your work. For this audience, first summarize, in your words, what you did.
Romesberg: Okay. If you’d start just very briefly, basically, all of life’s information—I think everyone here knows this—is encoded in four letters of the natural genetic alphabet that’s in the DNA, the GCATs. That’s why it’s these long strings that are then—and that’s how information is stored. It’s retrieved, then, by conversion of segments of that, which we call genes, into something called mRNA, and the mRNA is read in a series of triplets of three nucleotides of GCA or whatever, and those code for amino acids, and that’s what goes into proteins. And so what we did in my lab was get two artificial, unnatural nucleotides to form an unnatural base pair called X and Y—I actually never called it that. The literature—the media kind of—
Kirkpatrick: You never called it that? Oh my God.
Audience: What do you call it?
Romesberg: 5/6 NaM.
Kirkpatrick: Well, that’s why the media had to help you, man, come on.
Romesberg: And so we can call it X and Y here. And so what we got is—we found an X and Y, an unnatural pair of nucleotides that formed an unnatural base pair that, once we got them into E. coli and put them into the DNA, the cells stably harbored and replicated it and stored it, so they literally survived and grew and lived with DNA with increased information.
Kirkpatrick: And so what does this mean? I mean give us the big picture implication from your point of view.
Romesberg: The big picture implication—well, I mean I guess there’s a couple. There’s a conceptual sort of aspect of a big picture, where I think a lot of people—I mean the fundamental question in biology is why life evolved the way it evolved and why we are the way we are, and I think the most fundamental aspect of what we are is the information we store in our DNA and how we store that information. And I think for a long time there was this idea maybe that G, C, A, and T were there because everything in life has that. So let me be clear about that.
Kirkpatrick: In the universe, possibly, yes.
Romesberg: Everything that we know, all life that we know, and in fact, all life as far back as we can see, the last common ancestor of all life on earth, had a four-letter base pair of G, C, A, and T and that’s how it encoded information. And so there was this possibility that maybe GC and AT were the only solutions that were possible, there was something very special about those nucleotides and those base pairs, G pairs with C, A pairs with T. And what we’ve shown in my lab is that’s not at all true, and, in fact, the X and Y pair by completely different physical mechanism and they’re completely different than G,C,A, and T, and yet they function alongside with them just fine. So I think that from that perspective, it tells you that evolution, that life is a lot more plastic maybe than we thought.
The other perspective—we’ve talked a lot about therapeutics today. Protein therapeutics have become a real big deal lately and people have become really interested in that, but they’re very much limited by the twenty natural amino acids that you can build proteins out of. So if we can encode and retrieve and maybe even evolve proteins with twenty-one, twenty-two, twenty-five amino acids, multiple unnatural amino acids that were selected for their possessing certain properties that bestow the proteins with certain functions that you’d be interested in, either for a therapeutic goal or degrading—you know, fixing nitrogen or reducing carbon dioxide or whatever it is that you want—maybe you could then evolve proteins that function to do that.
Kirkpatrick: That’s pretty exciting. Just one final thing—and maybe anybody can chime in on this, although I want to get to each of you to some degree individually. But we’ve heard a lot today about two fundamental technology processes, which are sort of reading DNA and synthetic biology as sort of two gigantic freight trains of progress that are underway. Would it be your hope that basically you’ve identified something that is maybe a third kind of thing that could yield to all kinds of potential innovation and progress, based on truly artificial life? Is that sort of what you’re hoping for?
Romesberg: No. No. What we’re hoping for, and what we worked very hard to do was to make X and Y so that it can function along with G, C, A and T. In fact, I think this is sort of—
Kirkpatrick: It’s just the more complex form of synthetic biology.
Romesberg: Well, it’s an expanded form. So it doesn’t mess up what things do, what life does, but it increases the potential for what it might do. And I think that’s important. We’re a long way off from having a fully synthetic cell. In fact, I’ll say long enough that it’s essentially infinitely far off. It’s just too complex. But what we’ve been able to do is simply take the system that is there and add a synthetic component to it and expand the potential of what it could do and maybe be evolved to.
Kirkpatrick: But when you said synthetic proteins that consume carbon, I saw Stewart’s eyes perk up there, because that’s something he’s thought long and hard about, along with many other things. But certainly, we all think about that. Let’s face it, if you could come up with something that helped with that, we’re with you on that.
Brand: Wait, I’ve got an even deeper question.
Kirkpatrick: Okay, please, ask him a deeper question, Stewart.
Brand: You’re saying that GCAT, the DNA that life we know is based on, is a frozen accident? There were these four base pairs that happened to be the basic ones, and because they’re that basic, you can’t fuck around with them. And so everybody’s stuck with them. But they just happen to be what happened three-point-something billion years ago, and it could’ve been this other combination.
Romesberg: So the two extremes are that it’s an accident that we all got locked into, or that it was the only solution possible. And so what we’ve shown is that it’s not—no, let me be clear: We’ve shown that G, C, A, and T are not the only solutions possible, because we now have X and Y. We do not have an organism that propagates based on only X and Y, so we haven’t replaced the code in any way. All that we’ve done is expand it.
Brand: Do you conjecture beyond X and Y? Are there other possible base pairs? Do you think this is it?
Romesberg: Look, my lab spent fifteen years doing this, so I’m now going to move on to these other aspects that we’ve talked about. But what I will say is that if you think about it, fifteen people with—essentially, we’ve talked a lot about funding, but this was one continuous NIH grant from the government that I got when I started my lab in 1990—oh God—anyway, a while ago.
Brand: You told NIH you wanted to find a new base pair?
Romesberg: Yeah, and they funded it.
Kirkpatrick: Well, wait, finish your statement. So you’re saying—
Romesberg: So if my lab could do it in fifteen years, with no more than three, maybe four people working on it at a time, my guess is that there’s lots of other solutions out there. It’s nothing magic. It’s just underlying fundamental forces of physics and physical chemistry and the physical chemical properties of matter. Any force that you can harness that’s stable and selective that mediates the pairing of X and Y, and A and B, and C and D, and G and C, and A and T might be sufficient. We happen to use a force called the hydrophobic effect.
Kirkpatrick: Jim, I see you nodding extensively. What’s going through your head with this?
Flatt: I’m struggling here in terms of thinking about the evolutionary advantages that would give us our current four-base genetic code. And kind of Floyd’s thoughts on, with a different type of chemistry, hydrophobic interaction as opposed to hydrogen bonding, what you think the evolutionary advantage for the current kind of chemistry is and what the implications might be for evolution?
Romesberg: So the reason that we chose hydrophobic nucleotides in the first place, so that they would pair with each other based on oil and water—so I mean everyone knows that if you mix oil and water, that they don’t mix, they form two phases. And so water likes water and oily-like compounds like oily-like compounds. So the natural nuclei base is G, C, A, and T. As you mentioned, they interact based on hydrogen bonding and so that’s a very hydrophilic water-like thing. So we thought from the very beginning that we wanted to avoid mis-pairing with G, C, A,  and T, so we made the very hydrophobic analyte. So from that perspective, it might be very hard to make multiple hydrophobic base pairs. And so maybe from an evolutionary perspective, if you need more than two, maybe hydrogen bonding was a much better way to go and maybe that’s why nature went that route, because it was reliable. But in terms of the expansion, one hydrophobic pair was what worked, and maybe another hydrophobic pair would be challenging.
Kirkpatrick: Okay, we can come back to this, but—this is so cool, we could stay on this. But, Stewart, I want you to answer a kind of big picture question, since this is our big picture session, among other functions it’s playing. How big a change is biological science going to create in society in coming years, in your view? And why? In two minutes.
Brand: We don’t know yet. The inklings are huge. You know, we get a sense that, okay, these self-accelerating technologies, like digital technology, if they keep on doing it decade after decade, change everything. We saw it with communication technology, basically, with digital code. So now we’re looking at bio code. Is bio code the same or is bio code different? In some ways it’s the same. It is absolutely miniscule little distinctions, which, when read as code and played out, make huge differences that can be evolved upon and expand in all directions.
On the other hand, all the digital code that we know and work with is engineered, and almost none of the biological code that we work with is engineered. So you can’t reverse engineer what was never engineered in the first place. It’s kluges and patches all the way down, three-point-something billion years of mass, and trying to tease engineerable order out of that is in a sense what Drew Endy was saying—it’s trying to make biology engineerable, because right now it ain’t.
The thing which drove Moore’s Law—that Gordon was right about from the beginning—is that there was a pattern of chips having more and more transistors, basically, every year and a half to two years. Is there anything really equivalent to that in biotech? I’m not sure yet. For sure, DNA is incredibly tiny. We’re just finding out amazing new things that might be done with it, with this—and there’s big numbers down there. People have three billion base pairs, the passenger pigeons we’re paying attention to at one point three billion base pairs. We now have tools like CRISPR-Cas9 that can make individual changes at the base pair level. I’m still getting my head around how indescribably nearly invisible teeny and tiny that is, that you have these huge differences that come out of it.
So then what you’re speculating about is how does the amplification play out over time of the law that hasn’t been named yet of the self-acceleration of biotech. Medicine drives it, people who want to stop being so sick and impaired and would like to live longer and thrive better and be smarter and all these things. And there’s a lot of money there. So with de-extinction, we’re just drafting behind the kind of money and the kind of technology that George Church and others are doing basically in service of human medicine. That desire, that need is in place and will be there, I guess in some form, indefinitely. So that funding, that market, whatever that thing is that is drawing this technology towards it, is absolutely in play, same way it was for digital technology.
So the prospects are enormous. Whether it levels off in some way technically, I have a sense some of the panelists here may have an idea on that. So bio code is very similar to digital code, and is fundamentally different.
The other fundamental difference is, where one is about communication, the other is about life itself. You know, who we are, not just how we talk, but what we’re actually made of, how we grow. I’m reading a book called “Life Unfolding: How the Human Body Makes Itself,” and it’s—I studied biology fifty years ago over here at Stanford, and I had no idea of the profound simplicity and subtlety and complexity that an embryo goes through in the process of development—any embryo, shrimp or us. But we are now grasping that complexity, are able to model it. And big data and better modeling and all this kind of stuff is giving us a handle on things which all seemed impossibly complex before, and probably including ecology, which has not been a predictive science until now. That’s where I live.
So, yeah, the possibilities are spreading out, and this should be an extremely interesting century.
Kirkpatrick: Yeah. Okay, good. That was about as thoughtful as I could’ve hoped for, so thank you. But, Floyd, do you have any thoughts on that, I mean the scope of what may be possible just broadly in biological science?
Romesberg: I completely concur. And I think this has been said a bunch of times today: I think that we’re just scratching the surface. I think the tools that we now have, from genomes to—I mean I remember when I started in molecular biology—I was trained as a physical chemist. I started in molecular biology as a post doc, and you had to make all your own solutions. And so now everything’s a kit, so the sort of acceleration that sort of technologies have provided just for the day-to-day tasks of doing things. It used to be that sequencing something would take days, and now it’s cheap and takes almost no time at all. All of this accelerating, all the techniques, the tools, it’s pretty dramatic. So I mean I have no idea where things are going to go, but I think the tools are unbelievably powerful.
Kirkpatrick: Okay, now, Jim, your company is at a very early stage of doing a whole bunch of stuff. So when you hear Stewart say, “I don’t really know, it’s going to be … it’s certainly a problem…”—I mean what’s your sense of this fundamental question?
Flatt: So I, like Stewart, think the potential is reasonably unlimited and we’re going to see definitely an exponential increase in the adoption and impact that synthetic biology has in multiple fields. But there’s really going to be two things that are really going to limit, or at least constrain that rate of implementation, and the first is recognizing that synthetic biology, this description of technologies that we love, is still a tool. In and of itself, it’s a tool to solve problems, whether it be to deliver better healthcare or more economical nutritious food, or ultimately fuels or chemicals. And so each one of those industries has its own dynamics and infrastructure. So I’m going to cite a couple of examples, just to show how that plays out from our company, but that is clearly going to dictate the implementation rate. And I think that’s what the community saw when there was this sort of boom and bust with respect to biofuels. There was a lot of excitement about the potential, but not really a real good grounded understanding of the industry that we’re trying to transform.
The second piece is—and I think Floyd was touching on this, and I think Drew earlier—we’re still limited to a great extent by our understanding of the design rules. So we’re developing a lot of great tools to do bio-programming, but we’re still just scratching the surface of our understanding of the design rules and basically what to build. So at our company, we’ve made a lot of advances in making DNA and DNA assembly and biological structures faster, cheaper, and more accurately. But still, we often run into the same issue where, okay, how do we actually design something better than nature has already provided?
So to try to bring those two themes together, if we look at our company, our first two commercial—or what we believe will be our first commercial successes—kind of align with those constraints, and the first is on an industrial standpoint. Two examples: We have a partnership with Novartis Vaccine and Diagnostics, where we developed a new method to develop vaccine seed, to start the process for making a seasonal vaccine. The H7N9 virus and flu that you may have read about that arose in China, the technology and methods that we had developed to replace the sort of egg-based re-sort and genetic methods to get a starter seed to provide protection immunization against that strain, we designed that from scratch, using only the sequence that was actually transmitted over the Internet. And that’s what’s exciting, to show the real first manifestation of sort of digital biology, and the real advantage is that we’re able, without having that active virus, to develop a vaccine for that and do it in a shorter period of time than previously had been achieved.
Brand: How short?
Flatt: Six weeks. So when you’re looking at a situation like the previous speaker had alluded to with the H1N1 flu in 2009, that may have been a real difference maker to get out ahead of the curve. And so that’s a case where there’s already a manufacturing structure, and there’s information about what we want to build. We know what the virus is, we have it sequenced, and now it’s a matter of building it.
In our second example, we have a relationship with Archer Daniels Midland to produce certain nutritional products. And, again, in this case, here is an area where we can take all of our technology and what we’ve learned about making algae better and more efficient, and translate that to solve a problem and to utilize sort of an existing capital infrastructure. So we didn’t have to go out and raise hundreds of millions of dollars to build a new facility, but rather, we could drop in a cell line that would produce a product of interest.
And so I think those examples are real case studies about how this field is evolving, where we align, recognizing that we still have limited design knowledge and we have to look at the reality of the industry that we’re impacting. But make no mistake, that process will speed up because we have, in each iteration, we’re seeing a significant reduction in the time and cost to get to the same endpoint, and that’s what’s so exciting about this field.
Kirkpatrick: And just real quickly, that Archer Daniels Midland foodstuff creation process really came out of work you were doing with algae with Exxon Mobile on fuel production, which was a slower process that is not yet commercial.
Flatt: That’s right. So it shows how we can work to tackle the big, tough problems, and that’s ultimately—we’re still committed to doing that, but we also recognize that we’ve got to find a path of our own sustainability. If we’re going to transform the world, we’ve got to be financially sustainable ourselves. And that was a nice way we could really leverage some of the technology we had developed to develop a solution that could have a commercial impact shorter term, while continuing to progress the science with respect to the bigger problems.
Kirkpatrick: Great. So, Steve, one of the subthemes of the whole day is technology, IT’s role in driving all the rest of this. And your product is a key example of how that’s happening. How does Simulia play into this, and how does your thinking evolve, generally, about how technology, and IT as a toolset, is going to drive progress in biology, and what it might imply for where we can go?
Levine: That’s a great question. IT is an underlying enabler for everything we’ve been talking about today. It’s information technology, and that’s everything—biology is all about the information and the nature of life. And so we have a thirty-year history—although we’ve focused in the manufacturing sectors historically—we have a history of basically bringing digital technologies to disrupt markets that haven’t really embraced them yet. And that’s what we do. We look at 3D digital technologies and we look at markets that haven’t really embraced it yet but really should and we try to bring what we’ve learned from other areas to bear on those markets.
So we really see bioengineering and biology—which we’re approaching kind of more from the macro scale, top down, because that’s kind of where we come from. So rather than looking at the detailed biology inside, we’re looking at the end product, which is typically the human body. So we’re looking at digitizing and creating digital organs, fully functioning body parts that work on the computer, much like you would manufacture any other device, for research purposes or for manufacturing purposes. If you’re building medical devices that you’re putting in the body, you want a test environment. Well, today the test environment is typically a human. We call them clinical trials, but really, humans are being treated as laboratories. They put it in, you function, and people just record how it works. We think that that’s a little archaic. And we understand why it happens today, but we think we should commit ourselves to stopping that practice as quickly as possible.
So by building these digital organs and entire body parts, and ultimately full bodies, we think we can create digital laboratories. To house all that, you create incredible amounts of data, so you’ve got to understand not just the data itself, but what it means. And the impact of taking what we learn about creating these body parts and digitizing them and storing them in a meaningful way opens up an entire new perspective on managing healthcare and health data, because now if you’re understanding how a body is working and you’re using tools to diagnose problems, you can store that data, not just as information or numbers, but you can actually store the knowledge of how that person is functioning. And then, as others have talked about today, you can then start to accumulate that knowledge across populations, and more importantly I think, across someone’s lifetime. We go through a lifetime of testing. Each time I go to the doctor, he takes a test and that data goes somewhere. It used to be a piece of paper and now it’s a digital version of the piece of paper. But there’s no knowledge accumulated. So my healthcare should get better over time.
Kirkpatrick: So if we have a working 3D digital model of our own self, it potentially could be stored with restricted access to us, just as our DNA might be, as David Haussler was talking about earlier today. I mean we might have a really kind of fairly holistic repository of our own health data, even beyond what we’ve conceived of thus far.
Levine: Right, so you could clearly separate the unique parts that are personal about that healthcare record and the parts that are not, so that I could have a fingerprint of what my biological system looks like and the treatments and the outcomes, without any knowledge of who it was. So I have knowledge of who it was, but it then goes into a central repository that’s then available for people to study and say, okay, does my fingerprint look like anyone who’s had a fingerprint like that before? Can I learn from those patterns over time?
Kirkpatrick: Wow. So I want to switch to a different topic. It’s come up a couple times—I think Nancy set it up nicely. Really, I’m not a super like U.S. über alles person, but it is interesting to look at the state of innovation in this country vis-à-vis others, particularly China, which I happen to get a chance to go to fairly often. And they know this stuff is important. Let’s not pretend they don’t. And we do have an enormous opportunity for advance and an enormous feeling of potential resistance from the public, right? I mean both the de-extinction stuff you’re doing, Stewart, and the artificial life, Floyd, that you’re developing. Any time you talk about it—and I haven’t forced you to do it yet tonight¾but you have to spend a considerable amount of time explaining why you believe this is not going to get out of control and lead to horrible human catastrophe, the end of the planet, or whatever. And it’s not a crazy question either. But I guess it is a somewhat under-informed question, shall we say, in many cases, and the reason I’m going along with it—you know, when Beth Seidenberg and I were talking about it, we got into this education issue. And it comes back to so many discussions of U.S. competitiveness. But I’m curious for any of your observations on where you think the landscape, the political, social landscape, in the United States in particular, may be headed, as the pace of biological advance at least potentially accelerates even further.
Flatt: Well, if I could just offer a couple of comments, I think one of the things we’ve learned over the last few decades, and looked at how genetic and genomic technologies have been accepted or not accepted in different geographies and in different industries, it really comes down to a couple of core things. And the first is transparency and motivation, and the second is really around benefit. And this is an area where I think the industry collectively has not done as good a job as it can to communicate really the benefits from a societal perspective, whether it’s genetically modified crop or what have you. You know, what is that holistic benefit and why should a consumer care? That is the ultimate customer. And if there is a transparency and good communication about the motives, at least you take that trust issue and at least reduce it. And I think that’s been the root of a lot of the acceptance issues.
Kirkpatrick: Yes. This resonates with something, Stewart, you and I were talking about. The biotech industry, actually going back as far as Asilomar, has been thinking about some of these ethical issues quite methodically. But interestingly, there is not a perception that that has been communicated. I mean you made the point that the industry has been surprisingly responsible at internally debating these matters time and time again, right? And Floyd, I’m eager to hear any thoughts you have on this. Does the biotech industry, or industry broadly that’s a potential beneficiary of biotech, need to take a fundamentally different attitude toward the public in communicating benefits?
Brand: Well, one of the things you want to do is have something that’s adorable right at the start.
Kirkpatrick: We know that cat videos work.
Brand: There may be an avenue there I hadn’t thought of. But in vitro fertilization came along as a possibility some while back, and all of the “You mustn’t play God” stuff came up, all of the “There must be something wrong with the parents that would want such a thing” came up. “There’s certainly going to be something wrong with the children that would come from that abomination of”—
Kirkpatrick: This is twenty years ago or whatever.
Brand: Yeah, it was more than that. It was a way to reproduce humans. And then the first in vitro babies came along and they were healthy, and they were adorable, and pretty soon they grew up and voted. And suddenly that whole concern evaporated. So then you could do another kind of sociocultural economic analysis on what happened with genetically engineered food crops. And the shorthand, whenever I say GMOs are good, the answer always is Monsanto. Well, what the hell does that have to do with anything? It’s like saying Microsoft. It’s just a corporation. And you look at the anti-GMO movement, if it’s a sin against biology there must be lots of biologists in it. Well, there’s none. Well, if it’s a sin against farmers, there must be lots of farmers in it. No, there’s only organic farmers, who are trying to protect their weird marketing approach to life.
So what happened? I think you named it. You know, the transparency and motivation issues. It looked like it was just for profit, and it was behind a patent wall for a while of all this stuff. And so the sooner you can get this stuff outside of those kinds of packagings, probably the better. And so one of the greater attractions—de-extinction, by the way, has not met the kind of anti-GMO freak out, and I think it’s partly because we’re transparent. There’s no goddam commercial thing you can do with it. We’re making sure that you can’t. And all that helps.
So as this technology becomes less giant corporation—and it’s sort of amazing that the medical aspect of this has not been come down on strong, because big pharma looks just as bad as Monsanto, if you want to look at it that way—patents and trade secrets and all this stuff. But somehow, if the medicine actually works, people will put up with a lot.
Kirkpatrick: Well, you know, it also occurs to me, the bio hacker space could play a role. We don’t want them to be sanitizing the profits of big companies, but, on the other hand, as really a more egalitarian science emerges, it could really help. Any thoughts on this, Floyd?
Romesberg: Yeah, I mean you just covered a whole broad range of things. I guess let me say one sort of—I don’t know if this is appropriate or not—but one sort of dissenting voice from some of what’s been talked about today about sort egalitarian science or democratization of science. And this hints at something that Jim said: science is hard. And with all the information, all the technologies, the genome sequencing—and I said that was all revolutionary, all these great things are going to come. But still, it is really hard to actually understand how to do it. Biology, I mean I think as a chemist and I think—I remember when I was a bit younger, everyone said get trained as a chemist and then you can learn to do biology. And what you get from that is chemists who do terrible biology.
But biology is the least reductionist of all the sciences, because it’s so interconnected and so complex. And that just makes it extremely—you can write down a very simple equation, like a physicist would, or maybe even a chemist, and it just doesn’t work. And there’s a reason that people go to school and study and get their PhD, where they’re focusing on something for five years and really learning how to think about science. So I don’t want to be overly negative about that—and I love the excitement that this kind of public interest brings. And if nothing else, I think it helps to articulate and sort of get people out there who act as proponents of science and of doing good science and of not being afraid of science. And I’m not quite as sure that I rely on groupthink to run my science. But certainly, I completely agree that it is very important to demonstrate the utility in something, because then I think society will adapt to it, when they start to see that it’s not evil and that people are benefitting from it.
Brand: This is another difference between digital code and bio code. Digital code is really easy. Ryan and I did a hackers conference back in 1984 and there were people who just sort of learned code and two months later they were creating a significant new tool. Good luck with that in bio-coding. The sequence of complicated, incredibly arcane processes that—you know, just to discover them, you’ve got to find every false lead there is. Fourteen years, whatever it is, you know, there’s nothing but false leads out there. And you go through a zillion failures and partial successes that turn out to be blind alleys. It’s horrific.
Romesberg: And can I add one more thing, because it was really something that you said earlier about how—I think you used the expression, I don’t know, patches or something—
Brand: Patches and kluges all the way down to a frozen accident.
Romesberg: Exactly. And so people think this sort of notion of Darwinian evolution, that everything is adaptive and that everything builds one thing on another in a very logical way. Scientists now kind of understand, or at least think that’s really not the way it works. It’s a much more random process. And things that should seem so logical, that you should be able to intuit why they function a certain way, just don’t, and there’s just not that kind of logic underlying and it’s just this weird—what’d you call it, patchwork and quilts? I guess not patchwork and quilts. What was it?
Brand: Computer patches and kluges. But this is an important understanding. People think that nature is incredibly fragile and easily broken. We’re discovering¾oh my God, if you put a species out there that nature doesn’t know what to do with? Even though it was there for millions of years before we showed up. Nevertheless, they worry about that. And they worry that, you know, some random gene, a fish gene in a strawberry will destroy the world. And, one, they imagine that something very fishy is coming with that gene. It’s just really a little bit of code that says do this instead of that. It’s not a fish. That’s part of the misunderstanding.
The other misunderstanding, I think there’s a bad seed idea that there’s contagion, and that the wrong gene in the wrong place will destroy all life. There’s people like Vandana Shiva who actually say stuff like that. And it is based on thinking that I guess genomes are rational, instead of what Floyd just described. Genomes are garbage, and a total mess, a very dynamic, fast-moving mess. And they have one wrong thing go in there, it’ll just get absorbed. There is no one wrong thing you can do to a genome in almost every case. There are very few where one tweak makes a big difference. But it’s tiny.
Kirkpatrick: People have watched a lot of Hollywood movies is what you’re really saying.
You know, we have, according to this, one minute left. I’ll probably exercise my prerogative and go a little longer than that. But I want to hear thoughts from you. I think we’ve had a pretty damn good conversation up here for the last half hour.
Jorgensesn: Okay, on three different things that were touched upon just now—
Kirkpatrick: Okay, I don’t know if three is allowed, but—
Jorgensen: Okay. Really fast, I was going to have my picture taken with you, Floyd, because you may not know it, but you are a superstar in the citizen science world. The fact that you had created another base pair buzzed around all of our message boards and everything else. So if nothing else—
Kirkpatrick: And now he’s dissing you guys—
Jorgensen: You’re getting really great PR and you’re dissing us. So the thing about science being really hard, number two, if anyone heard what Drew Endy was saying about abstraction, there’s a long game here. There’s a game that needs to make it more accessible and less hard to engineer. It isn’t here yet, and it may take a long time, but it is going to get there.
And the third thing, the thing about safety: Anything that inherently self-replicates, people are not going to be comfortable with. But the thing that keeps coming up over and over again, and even George Whitesides, I thought he wanted to talk to me about DIY bio. He wanted to talk to me about the risk of DIY bio. And I was very disappointed, because there’s one example they keep bringing up of an immune system gene in a virus or a bacteria that I think the Russians did at some point, and that made a tremendous difference in the pathogenicity. And that same example keeps getting pulled up over and over and over again. So I agree with you, but we have to have a counter message. And I agree that DIY bio is part of it, of course.
Kirkpatrick: Okay, I love that that’s more of a comment than a question, which means we can go to the next one.
Palmer: My name’s Megan Palmer. I’m at Stanford, at the Center for International Security and Cooperation, and work with the Synthetic Biology Engineering Research Center. My question is: What do you guys see as the key decisions we now are facing in terms of how we build the human infrastructure for biotech? What are the key choices in terms of how we cultivate the people that will be part of the next—
Kirkpatrick: Is that an education question?
Palmer: It’s not education—it has to do with some of the comments that Drew Endy was making this morning as well about what types of organizational forms and who are the people that are going to be able to architect this trustful relationship with the public around what biotech can do. Is it the biotech incubators, the DIY biotech, is it companies, is it some sort of other organization that can gather the strategic leadership of the field? What types of people and what types of organizations can do that?
Kirkpatrick: That’s a challenging question. Who wants to grab it?
Brand: David, that’s your kind of question. Come on, moderator.
Kirkpatrick: Well, I’m supposed to ask it. I mean I don’t know the answer to it. But I mean it’s interesting coming from someone in a security related—
Brand: Yeah, we were expecting the usual, “Where’s the bio war”—
Kirkpatrick: No, but I think it’s very security-related, actually.
Levine: I think the short answer is all of the above. I think what we’re talking about is a total mind shift in how we view biological engineering, not as a threat, but as a benefit. And that is a systematic problem that we have to change the thinking of. And I think there’s a generation that’s growing now that completely embraces innovation and knowledge and information, and I think we need to cultivate that, beyond just playing games, but actually using it to improve the world.
Flatt: And, Steve, to that point, I mean if you look at culturally, at least what I see in my daughter and the kids she’s going to school with, there are two things. One, they are, I would say, much more interdisciplinary and open to ideas from all different sources, nontraditional learning and not thinking about things in such regimented ways. And secondly, they’re very communicative, probably more so than you’d want, but that actually does seed some good things when you’re looking at trying to improve communication to the general public about articulating benefits of technology and what problems it can solve, and the actual measures that are being taken by a lot of groups to ensure that it’s being done in a safe and sound manner. So I think those are elements that can be built on. The right organization or organizational structures is probably a question for others, but I think those are some good seeds to build on.
Brand: I think some right things have been done in the context of sort of biosecurity and organization. Back in the late 1970s, early 1980s, when computer hackers were first happening, the FBI came down on them heavy and put some, like Captain Crunch, in jail and so on. And that’s not happening with bio hackers. And indeed, the FBI, instead of coming on with total angry ignorance, like they did with the computer hackers back when, are coming in with quite a lot of sophisticated knowledge, and openness and curiosity to the iGEM Jamboree, and there’s probably some guys here like that. Are there any FBI people here? You can say. NSA you can’t say, but FBI you can say. They are showing up at gatherings like this, and passing out their card, which says, you know, weapons of mass destruction, FBI, so and so. Because they know that the practitioners—as was the case with the computer hackers—are the ones that know where the actual potential bad news is coming. They are the outliers who are trying stuff and hearing stuff and evermore communicating stuff globally, and if something weird turns up they will be the first to know. And for a change, the government—at least the U.S. government; I hope other governments—are saying, “We’re not going to hurt you. We know you don’t want to hurt the world. We would like to help you in that motivation and make sure that this wonderful technology that you love and we love, doesn’t hurt people.” And so there is this relationship between the establishment, the government, the big, slow, grinding, decades-behind government, actually staying pretty current. And Drew Endy and—
Kirkpatrick: But, Stewart, I’ve got to say, that so much of that is driven by this excess reaction to terrorism and a fear mentality, which is what has got the government focused on this, as opposed to what they might be doing in China, where they say, “Our country is going to in the next five years develop fifteen or twenty of these new labs, and we’re going to train 75,000 scientists….” That’s not what we are doing. Our government is not taking that—I mean it’s true, maybe they’re curious, they maybe are trusting of some people in this room. But, I don’t know, I can’t be quite as excited about it as you are.
Brand: So you think the government’s screwing up?
Kirkpatrick: Well, I just don’t think you should give the government any more credit for continuing to think that terrorism is the only thing they need to worry about, which I’m afraid is way too often the case in a lot of government behavior.
Brand: Well, there’s bioterror and bio-error, and bio-error can be even worse, because nobody sees it coming. It just turns out to be there’s something that got out of the lab—you know, we spend a lot of efforts to make sure they don’t get out of the lab. They get out of the lab and it’s a problem. We don’t know what it might be, but, you know, after the fact, it’d be hard to undo, unless you have a lot of people paying attention to bad news that shows up.
Kirkpatrick: I’m not saying we don’t need to combat the evil that was mentioned earlier. Did you have something? You were making interesting facial expressions.
Romesberg: No, I’m just listening.
Kirkpatrick: Okay, I am going to get in trouble with some of my colleagues if I don’t wrap it soon, but there are a lot of hands, so—does anybody actually have the mike? Okay, yes.
Chew: My name is Robin Chew and I’m a candidate for Congress. And so it’s very interesting, some of the questions you guys have been asking, and I’ve got fifty million ideas running around in my head. But what we face in politics is this whole idea of disinformation and how people use fear factors as a way to motivate people’s political behavior. And this is ideally made for the conspiracy theorists out there that are concerned with how synthetic biology is going to destroy human life. I’m a Republican, and it’s especially almost epidemic in Republican circles that they use fear. And I’m just wondering how, as a politician, we can make rational arguments about the kinds of things that you’re talking about, which are game-changing in a positive way, to make all our lives better. It’s really hard to do in politics. Fear is a much more effective political tool.
Kirkpatrick: That’s another version of the same question she asked.
Brand: Get Barlow to respond to that. He’s a Republican again.
Kirkpatrick: Okay. You know, I didn’t know Barlow was here until about ten minutes ago. So he should grab the mike, since he was originally going to be on this panel.
Barlow: Well, you’re absolutely right. And I also want to say that I agree very much with Stewart about how encouraging it is that the government hasn’t jumped on desktop bioterror as the next tool of the bad guys. But I mean, actually, I believe that you’re right, David. The real problem—the terrifying problem, to me, is that the government isn’t taking this stuff seriously at all. And it takes a long time to develop. As somebody who is doing a biofuel that I think is actually going to make it, but has to make it in a timeframe that is much different from anything you can do with bits, it would be great to have actual government assistance that was meaningful and wasn’t just sort of nest-feathering on the part of the DOE and the consultancies that form in the immediate vicinity of the DOE. So there’s a lot that the government can be doing with biology that’s positive that they’re not doing. So, yes, I’m glad they’re not completely freaking out in the way that—you know, when EFF got started, the Electronic Frontier Foundation, it was because they were—I had a visit from the FBI where I had to spend two hours with the guy explaining to him what the crime was before I could start telling him why I wasn’t the guy that had done it. You know, that stuff is really kind of scary, to get that many well-armed, insecure guys wandering around someplace they don’t understand. And there is room for fear in the general vicinity of bad bugs.
But, as you say, bad bugs, Stewart, are not that easy to make. And we need to—
Brand: Good bugs are hard enough.
Barlow: I know. And we need to be able to make good bugs and get some government help in doing the good bug making.
Kirkpatrick: Okay, we’ve got a desperately waving hand over here—and this is going to have to be the last comment or question, I’m afraid.
Jankowski: Perfect. This one involves the audience. My name is Tito Jankowski. I’m one of the cofounders of BioCurious, and my question for you guys up on the stage, as well as everybody else, is: Have you been to a biotech lab before in your life? Whether it was high school or a community bio hacker lab—everybody raise your hand. Maybe we’ll redo this next year—what does that look like?
And then one more is: How many of you have ever transformed a bacteria? So that means taking DNA and putting it in E. coli or something else. Okay, so two up on stage and 50% in the crowd. Cool. Thank you very much.
Kirkpatrick: Does you understand why he asked that? You’re just doing a research study, okay.
Audience: I’d just like to pick up on something that Steve Jurvetson said. Information economies tend towards income polarization unless we innovate for inclusion. So the question would be is there something we can do to use synthetic biology to produce extremely affordable products for people in shantytowns in Johannesburg or Rio de Janeiro?
Kirkpatrick: I think you should repeat. I didn’t quite get that, I’m afraid, through the accent. You might have to repeat that again, a little more slowly.
Audience3: The question is: Can we produce extremely affordable products for people in shantytowns, leveraging synthetic biology? For example, with biomaterials to produce houses, or to produce extremely affordable food for people in shantytowns? Because if we can do that, we can use innovation to create inclusion.
Kirkpatrick: So can we really use some of these tools to build products that really help the very poor, I suppose globally, is what you’re really referring to. That’s the question.
Brand: Yes.
Kirkpatrick: So there, somebody said modified bananas have been shown they can help cure blindness.
Romesberg: You ever heard of penicillin?
Kirkpatrick: Yes, there you go.
Romesberg: Flood-proof rice is out there.
Brand: Golden rice, for sure.
Kirkpatrick: Yes. And that rice is now controversial.
Levine: But you can do it.
Kirkpatrick: Well, it certainly changed the world. We know that. I thank the panel. We’ve got to wrap. This is great. This was a wonderful discussion, and I thank you all for participating in it. I thank Barlow for being a spiritual participant.
So basically, this is the end of what I think turned out to be a great day. In our opinion, it’s the beginning of at least an annual thing, maybe more often. We hope that you all will give us your ideas about people we should include, ways we should proceed, companies, ideas of topics, themes, whatever. We’re really open to your input, so please give it to me or other members of the team who are around.
I want to really thank Dassault Systèmes, represented on stage. And also the heart out there is an example of what he was talking about before, so you really should check that out on your way out if you haven’t already.
McKinsey and Company, Scientific American, the Bay Area Council, Collabria, and Startup Product Academy all helped make today possible, so thank you so much.
We have a reception now and we will see you there and again next year.


Floyd Romesberg

Associate Professor, Chemistry, The Scripps Research Institute

Jim Flatt

President, Genovia Bio, Synthetic Genomics, Inc.

Steve Levine

Chief Strategy Officer, Dassault Systèmes

Stewart Brand

Co-founder, Global Business Network

David Kirkpatrick

Founder and Editor-in-Chief, Techonomy

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