The Evolving Nature of Synthetic Biology: A Panel Discussion on Key Science, Policy, and Societal Challenges Facing the International Community
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The Evolving Nature of Synthetic Biology: A Panel Discussion on Key Science, Policy, and Societal Challenges Facing the
Remarks
Science and Technology Adviser to the Secretary
I would especially like to thank some of the people who helped put this on first. My good friend
And several of the speakers were involved in a report that just came out, the symposium report from the National Academies, called "Positing Synthetic Biology to Meet the Challenges of the 21st Century." It's a very interesting report; I just finished going through it, in fact. And for any of you that are interested, it's available; it's a free PDF if you go to the
Synthetic Biology, in my view, as some people have called it a disruptive technology, is a technology that can potentially have great impact on societies, and create opportunities, as well as create challenges. Certainly, the potential to have impact on international relations and the relations between countries. It's certainly become a topic of interest here at the
The panel today is going to address three issues: first, the state of science versus synthetic biology; second, the policy landscape; and last, what could be the societal response to this new technology.
It certainly is a very fast growing and internationally diverse field of research and development that has the potential to transform the world's bioeconomy. Over the last decade, industry has made significant investments. Governments are investing in fundamental research in this area, and I certainly believe that smart governmental policies will be needed, including to engender the trust of the public in dealing with the full potential of this emerging field. So I'm looking forward very much to learning more about synthetic biology today from our experts.
And lastly, I would like to introduce our moderator and my colleague here at the
Just to say a quick word about how we all got here: I think folks know that what we're seeing, or the topics that we'll be discussing here today stem from, at least initially, discussions that took place in June of 2009, where the National Academies of Science,
Let me just go over the structure. So we see four chairs here; we'll get to that at about 11:00 today. We're going to ask each of the speakers to come up individually and present their remarks for about 15 minutes or so, and then after that, they'll join me on stage and we'll have a discussion with the audience, with your questions. We have microphones, so please keep in mind that we'll ask you to go to the microphones and say something, if you have a question to ask. And the reason I'm giving you this introduction now, is so you can, while you're hearing these things, think of your questions and then go up to the microphones. So that'll be the format, and we'll try to wind things up at 11:30.
There are members of the press in the room, so you ought to, all of you just be aware, that any question you ask, there are others who might be listening, and using it for other purposes. So keep that in mind when you ask your questions. And, with that, let me turn now, let me turn now to our first panelist,
Drew is going to give the overview on the science issues of synthetic biology. Drew runs the world's first fabless genetic engineering lab and the new bioengineering program at
Let me introduce, now, Drew, and ask him to come up here. Thanks, Drew.
[applause]
At an abstract level, it basically collapses into science and technology. From the science perspective, we're 70 years into taking molecular biological systems apart and seeing what the components are. We learn about biology, historically, going back to the 1930s, by disassembling living systems. Synthetic biology allows us to reassemble things and see what happens. That is a very powerful approach to learning. It's a complimentary approach to learning. From a
From a technology perspective, as an engineer, we have a long-term goal -- this might sound weird to you -- we would like to make living matter programmable. Not just express a few genes here or there, but partner with biology to reinvent how our civilization works in making the things we need. Not to change ourselves or the world, but just to make things work a little better. Let me give you an example: in
All right, so somebody who -- that likes to build stuff, how do I do something useful with this manufacturing capacity that takes natural resources, the sunlight, the water, and the carbon and other things and manufacture stuff? 16 million pounds a year is a lot of matter. The world's chip supply for microprocessors adds up to be about 1 million pounds of engineered matter a year, engineered silicon. All right, so the manufacturing capacity of
So what would it look like if we advance a synthesis of biology to support manufacturing? Well, it turns out you can grind up trees into saw dust and regrow stuff from that. So this is in
What if I put bio-mineralization into an engineered wood fungus and begin to reprogram how I manufacture an object like this? That would be fully programmable manufacturing, using biology. Of course, I'd need to have program pattern formation, control how shapes grow over time. This worked for
Okay. Well, we're 40 years in the genetic engineering, so this is all working. Except, it's not; why is that? In part, because not everybody's been working on it. So for example, a textbook in bioengineering, my field from only a decade ago, if you start to read this one in particular, the third sentence in the first paragraph reads, "We exclude genetic engineering, that is systematic design of phenotypes by manipulation of genotypes, from the field of bioengineering." There's lots of good stuff in this book around medical imaging, artificial joints, and so on, but many engineers haven't yet engaged in the engineering of biology and synthetic biology represents that immigration within the engineering community.
In
The motivation here was basically to navigate an engineering process cycle, design-build-test more quickly. All right, so could we use DNA synthesis to separate design from fabrication of genetic stuff? Could we standardize how we measure and reuse things? Could we abstract functions to make design more powerful? I'll come to this very quickly. If you haven't seen this before, these bottles represent chemicals called phosphoramidites. There's four bottles. We're talking about biology, so it's got to be the four bases of DNA. If you organize these chemicals in a nice way and feed them into a machine, called a DNA synthesizer, you can then ship information into that machine. The chemicals would be dispensed in a way that assembles a custom polymer that allows you to build genetic material from scratch. Period. You then take that genetic material, if you can put it back into a system, it might reprogram the system, depending on how good you are at designing it. I view as the most important technology for the planet for the century. It allows you to go from abstract information on a network or a database to physical genetic material.
We're getting better at building things from scratch. So in 2004, biggest thing reported built from scratch was 10, 000 letters. In 2010, it was a million letters; not quite sure where that's going to go, but it's an interesting pace of improvement. Why does this matter? To a researcher like me, when we did our first genome redesign project, now almost 10 years old, this is how we had to assemble the DNA. And I won'read the whole paragraph, but what this represents is three person years of work, manually manipulating genetic material, to make a 12 kilo base fragment of designer DNA, cutting and pasting, using the tools of genetic engineering. What DNA synthesis does is it replaces that paragraph with an order through an Internet and a credit card, and says, "Please get me my DNA." That's a big deal. Right. It allows me to focus on being a designer, or a tester, or something else. It's a bigger deal within the context of policy for this reason: when you take synthesis of DNA and combine it with sequencing, that allows you to go from a physical bit of genetic material. You sequence it and now it's information, and it can exist as information throughout the networks. So I could be in Singapore and sequence something, and here in
All right, if you want to keep track of small pox by locking up the physical small pox, that's one thing, but what if the sequence is on the Internet for the genome? Hmm. So recombination of matter and information is a big policy change driver, and I don't know all the ramifications. I just want to try and say that out loud; maybe we come back to it, maybe you can figure it out. I'll give you a funny way to remember it: So this guy here is marketing something that's manufactured in a central location and then distributed as material. In a fantastic future, imagine being able to reprogram the microbes that live on your skin by downloading DNA off the Internet and synthesizing it wherever you are, and now you have a living perfume or fragrance. Right? So instead of shipping physical material, Chanel is shipping information over the network via distributed manufacturing in situ.
That's what synthetic biology can get you. Not that I'm advocating for this particular example, but to give you a sense that you might remember when you recombine matter and information and how that impacts material supply chains, lots of things change.
Okay, standards real quick. This is an object made from standard rocks. Standards are a way of coordinating labor among parties and over time. They're very, very powerful, very soft type of network power. When it works, you enable impossible things to happen. Somebody could pour the rock, somebody could assemble it, we could fix this aqueduct 2, 000 years after it was built. In synthetic biology, there are four areas of standards that have been developed over the last decade: layout of genetic stuff, composing parts to work, measuring things inside cells, and how you share information over networks. There's probably going to be a lot more standards. Who controls the standards, how the standards get promulgated will create a type of network power that we want to be mindful of. It's very important in my position that these standards remain open and scaling and that they're used constructively.
This technology has also been technically controversial within the research community. I just want to call that out and say it plainly. For example, the idea that you can standardize biological parts and reuse them, that you could abstract things, doesn't always work. Biology is too complicated, and you can see that represented within the field. I'll simply report that over the last year, it's now been shown that standard parts can be made to work, including for categories of elements that have been declared to be impossible to standardize. And
Okay. Abstraction, this last idea. Wouldn't it be neat if I could design, for example, a tumor destroying bacterium, without having to know that DNA is made of four bases. I would just as a designer say, I need a sensor to this type of tumor. I need some logic. I need some other things. I'm going to call down to the people who are expert at designing those things, and they're going to work with the biochemists and geneticists who can make those functions. Eventually, somebody down there will make the DNA, but I'm just going to be the high-level designer working up-top. Much like if needed to text my mom a photograph of all of you today, I wouldn't need to know how the machine code works to send that over the network, I would use a high-level language through this touch interface.
Could we do something like that? In biotech, examples again showing that this is not impossible, so for example, when logic was bootstrapped in the 1850s and then implemented in computing, that became very powerful. We now have examples, for example, electronic logic based on three terminal devices, like the transistor. Very recently, we've implemented molecular architectures like this for controlling computing within cells; we call it the Transcriptor. And basically what we've been able to do is recapitulate Boolean logic but in a new form that operates in DNA. What's interesting about this work is not just the computing outcomes, but the fact that when we did this work, every DNA design we made worked the first time. We didn't have to go around the design-build-test cycle hundreds or thousands of times. It took us three months to do this work from when we started the project, and we were, from doing that, able to demonstrate amplifying switching and logic gates.
From genetic engineering to synthetic biology. So let me try and wrap up and zoom out a little bit. Here are some of the core tools that powered the last 40 years of biotech: Recombinant DNA for cutting and pasting existing material; PCR for amplifying genetic material and recombining it; and sequencing, for reading it out. What is hidden within synthetic biology are initial and advancing new platforms supporting the design-build-test-learn cycle, and the scientific discovery process. So for example, synthesis of DNA. Although the chemistry for DNA synthesis was perfected in 1982, the process engineering around building larger and larger fragmented DNA hasn't really been invested in until very recently. It's not like the genome sequencing projects where the government said every base pair in the human genome is worth
Abstraction for managing complexity allows more people to implement more powerful DNA programs and standards is a way of coordinating labor across time and over locations. Significantly, there's a dot-dot-dot here, and what also is represented within synthetic biology is now sort of irreversible community of engineers, who are continuing to invent new platforms and tools for engineering biology.
Last slide. As this has happened, we've grown the community. All right, so iGEM was mentioned in the introduction. There's now about 15, 000 students all over the world and at least 40 countries who have gone through a cooperative genetic engineering competition. It used to be run out of
What would I want from my colleagues at State? Here's a list and here's my naive academic degree of difficulty scoring. Very important to prevent the remilitarization of biotechnology. You're probably already doing that; I just don't want to take it for granted. Right. It's something that has been underway for a long time. It's very, very important that we don't stumble back into that world view, with better tools. Along with that, there needs to be a strategy for biosecurity, in a world where we get better at engineering biology, and it's not obvious we have that in place yet. It's very difficult to talk about that, politically. We have to absolutely preserve and protect natural biodiversity. As an engineer of biology, I'm really bad at engineering things from scratch. I'm really good at taking things from nature and repurposing them, so I have to be the most powerful advocate for natural biodiversity on the planet. You'll see within the CBD, I'm sure, things happening around synthetic biology and people expressing concern around that. That's important, too. I just want to make a straightforward argument: we have to preserve biodiversity.
There's a thing reemerging right now: GMO versus no-GMO. That's a caring ford of an old debate that's kind of dysfunctional and it would be nice to transcend that; I think there are ways to that. As we get better at engineering biology, it's important, going back to the third point here, to not merely industrialize nature, but to reinvent how our civilization works and partnership with nature. What do I do with the garden clippings from
Some of the things are actually quite doable. This last one I gave as a easy task. Make human civilization work really well, it's because I'm optimistic, but I think we can do it. Thanks very much.
[applause]
[laughter]
Let me now introduce
[applause]
So first one. First one, as really, as Drew began to mention, synthetic biology is really emerging in a international context from the start. There are at least forty countries that have significant synthetic biology research programs ongoing. Probably more than fifty at the synthetic biology SB6.0 conference, global conference that was just held in
So let me just quickly mention a few. For example, the
The OECD, as Jonathan just mentioned, I have the pleasure to be the chair of the
But what's really interesting to mention is that some of the greatest emphasis on synthetic biology is occurring in emerging markets, and as part of their national innovation and economic growth strategies.
But it's not confined to
So the second reason, obviously, that this really matters to State and American foreign policy is around the economic dimension. Economic competitiveness, new export markets, trade policy: there just are a broad range of synthetic biology applications, markets, and business models that are emerging. And, as Drew mentioned, our colleague on the
And obviously, the size of these markets are huge. Nobody knows what the number is. There are numbers out there, that for example, that there may be a trillion dollars in global synthetic biology markets by 2022. Do we know? No. We just know the number is very big, precisely because it cuts across so many domains. Not only of energy and health, but we're already seeing, for example, a huge adoption and rapid diffusion in industrial biotechnology value chains, where synthetic biology processes as well as products that come very important, but there are also a broad range of health applications. For example, and new drug discovery and development, in addressing neglected diseases and responses and more rapid development of vaccines. And also very importantly, just in understanding basic biology in new ways that will advance health.
But beyond, sort of, the product and application side, I think it's really important when we think about the economic policy side for the U.S. to realize that it also creates new growth markets that are not related to specific industry applications. So for example, we have a large number of very competitive U.S. companies in computer-aided designs. All of a sudden, as Drew was just mentioning, we now have the development of CAD-like tools and software, with significant market potential. So a company like
Three final points on the economic side, before moving on a couple other issues: one is that, I think it's really important to understand, that a lot of the synthetic biology things have multi-use core platforms and infrastructure as part of the business model. This is
And then finally, obviously, potentially the biggest killer app of synthetic biology for
So clearly, synthetic biology very much links to concerns about sustainability. It provides a platform, a set of technologies, new advances that can basically help us address almost all of the issues that
Fourth area I want to talk about, and this I think is particularly important, and I think has been overlooked to a far greater degree than it deserves to be, particularly in the U.S., which is the role of synthetic biology for U.S. development policies. It's really a problem-oriented, solutions-driven approach. Just think about agriculture for a minute. This a core technology platform that offers one part of the solution for the next green revolution that we need to see in agriculture and food. One of the big issues is sustainable intensification for small-holder farmers, for example, in
And a little further out, is this whole idea that some teams, like
But also from very specific U.S. interests, I think it aligns incredibly well with a large parts of the U.S. development agenda. And I'll just use
The point here is that synthetic biology has something to contribute, whether it's on the global health initiative, on the Feed the Future initiative, a whole range of USAID things that I think we need to explore to a much greater extent than what we have before. And on the development side, it also offers a whole new range of potential toolkits and drivers for development. So thinking about the oceans, and the algae, and the biomass and how both for food and for chemical, et cetera, that that offers a range of new types of activities.
Clearly, the security issues are front and center, and they deserve to be; they're legitimate. But there's a range of them, and we need to be thinking about that in a very integrated and coherent way. On one level, of course, we have the biosecurity issues and particularly the so-called dual-use research of concern. NSABB, Drew, as a member, had a report in 2010, and there's a range of issues about who manages these risks. For some in the room who are in involved with
Beyond the biosecurity side, we have all of the traditional biosafety issues related to biosafety and error domestically, with the NIH guidelines and elsewhere. Be we also and I'm going to come back to the
And the last point I want to make about security is that we have also a number of nontraditional global security issues emerging around synthetic biology. So the interconvertibility between the physical and digital world that Drew just outlined introduces a whole new range of, sort of, cyber-biosecurity sets of issues. And then on a different dimension, obviously, resilience is one of the major new emerging security issues for the 21st century, and synthetic biology has a lot to say about a range of resilience issues. The
And then, because synthetic biology really is a tools revolution, I think it offers huge opportunities for U.S. science policy, in terms of new types of international research collaboration, shared infrastructure, capacity building. Drew heads the Stanford BioFab; why shouldn't we be thinking about developing BioFabs that are open and accessible, to promote synthetic biology in constructive ways, on a much broader basis, outside of
Very briefly, just all of the types of issues we have here are also transforming a range of other policy issues. Obviously, we have a new set of regulatory conflicts and disconnects, not only domestically among our regulatory agencies, but internationally. We're going to have a new wave around precaution. We're going to have issues around whether or not regulating the technology in synthetic biology exceptionalism. There's lots to trade policy and regulatory things around techno-protectionism. We obviously are going to have turf wars and jurisdictional issues that are going to, from an international side or, have to be addressed. We have this big lag between the regulatory science and where academic and commercial science, technology, and engineering are today. And then finally, I think, we also are beginning to see early stages of some countries and some groups who really want to use regulation and risk management techniques as a way to constrain or to slow down perceived American leadership, economically, and scientifically in synthetic biology.
And so for example, there are going to be a range of new regulatory foreign policy things around international treaties in the conversation and later we can come back to, but for example, there's a whole range of activities on the
And then, finally, I think that we need to be thinking, we tend to forget the investment side. And the international investment, public-private partnership funding issues are absolutely critical if we're going to successfully scale synthetic biology for beneficial applications, and also to de-risk synthetic biology investments. So again, very quick whirlwind, and I hope we can return to a number of those issues in the discussion. Thank you.
[applause]
[applause]
So it all started when, a few years ago, I began to listen to researchers at
So let me jump in and tell you about my first visit at
Well, scientists are constantly questioning their computing and engineering models. They are dealing with high uncertainty and high complexity. Just have a look at this quote from interview with a scientist at
And the next issue is what happens outside of the lab. And outside of the lab in the public sphere, we don't measure the uncertainty and the complexity. This cartoon was published in
Let's start with the media. Since 2008, press about synthetic biology in
On
So let's give a closer look at some of the narratives of control as they are used in the media and sometimes in policy discourses. In the New Yorker in 2009 you had, "cells has hardware," "genetic code as the software," "to write programs to control genetic components," "alter nature", "guide evolution". In Nature, "what can synbio do for us? Move genes around cells, create biological circuits, write new genetic programs that will change the world." Then, at a
Now, let me gloss over a few variations of this narrative of control that I find interesting for two reasons: first, because they got international coverage; secondly, because they use the distinction between an old way of doing science and a new generation of biohackers in synbio. So the first one is what I call the entrepreneur-scientist. In
Then the last variation is what I call the biogenius. So opposed to the Venter model, funded early on by big corporations like Shell, Chevron, and
So what do these stories have in common? They all leave a potential failure to control for implications of emerging technologies. Failure to ethics, failure to anticipate, failure to control; these are deep, deep control narratives. And they are deep because they're built on precedent failures, like DDT, Chernobyl, the oil spill, recent flu outbreaks. You have to remember that narratives are key in human cognition. We are the species' storytellers, and the stories we tell shape our perceptions. People trying to make sense of new technology will fall back on narratives long before they pick up a biology book and try to learn about the science.
So that leads us to U.S. perceptions. I summarized four years of U.S. perceptions to these and here are the take-home messages. People know little about synthetic biology, with 23 percent in the U.S. and 17 percent in
On that note of course, applications matter. People mostly care about applications which have a significant duty for society, medicine, and the environment. So flu vaccine, cancer research, biofuels are more compelling than trivial projects. When it comes to risk, biosecurity raises a lot of concern in the U.S. People fearing dedication to bioweapons. But they also have concerns with biosafety. So they would say, for example, could see moving to horozontal gene transfer. Something of that sort. In general, what they emphasize are failure to control for long-term implications, "what if" scenarios, and governance failure. So you could get a question like, "If a disaster happens, who is in charge? Can they fix it?" and, "How much is it going to cost?" If we glance over a few comments we got from our focus groups, you get: "I am worried about self-replication." "How do you control that technology? How do you stop someone from cloning a human being? How do you regulate that?"
"There are no safeguards. There are no understanding of the repercussions." And then this one is really interesting: "If there is not someone in their group who is asking, 'should we do this?' they need to include that person." So they are not asking for banning the research, they are asking for continuing oversight, transparency, and regulation. And they are also asking for benefit-sharing. And when it comes to benefit-sharing, the level of trust and cooperation was usually pretty low, but in 2013, the level of trust in the government and in NGOs dropped significantly. As you can see on this graph, it's kind of, it's pretty low. So I mean, what they are telling us is go for what was designed, but anticipate implications upstream in the process, and take responsible measures. And indeed a key issue in synbio will be trust, whether we trust the people who are essentially developing the technology, promoting the technology, or doing oversight on the technology. And then we have a lot to do with how much social capitol is in your society; there are huge variations. There might be much more trust in
So where does that leave us? Well, people are going to ask pretty hard questions about who is doing science, who is funding it, who wins, who loses, and what can go wrong. So in that context, there are a few pressing societal and communication challenges we need to tackle. First, it's never too soon to tell. We need to address the potential for failure to control. From the lab to the federal agencies, we need to get better at anticipating implications, biosecurity, and biosafety, upstream in the process. Ideally, at the level of design, but for sure before commercialization. So to that end, at the Wilson Center, we had a few experiments with what I call trading zones. These are open spaces where scientists from different disciplines and policy makers can share knowledge and question their designs to better anticipate implications.
Then secondly, well, we need to address narratives. We need to get better at communicating what an amazing revolution synbio is, but be open about uncertainty and complexity. And it's not a question about of public acceptance, it's a question of transparency and knowledge sharing. It's about a future where knowledge and funding can begin for crowdsourcing. It's an open future. Finally, we need to be thinking about ownership models that promote openness, innovation, benefit-sharing, and avoid inequality. And that has to be done in an international context. Just to give you an idea, two of the biggest genome sequencing facilities are in
So to conclude, I would just we still have time to address narratives, but that requires vision and engagement, not false promises. The public must believe that effective regulation, technology assessment, and public engagement is part of our science policy and not an afterthought. Thank you for attention.
[applause]
First question; please identify yourself when you ask your question.
[affirmative]
[laughter]
But, appreciating that's a displacement. All right, you know, if you think of
Two papers published in the last year show using synthesis of DNA is archival data storage. Right, so for about
Nobody at the early stages of ARPANET clearly could foresee the power it was going to be. I was very involved, being so old, with a lot of the government semiconductor issues in the late seventies to the early eighties. And you know, even
So the impact of that on the U.S. graduate students and post-docs is quite impressive. We don't have a political leader like that standing up for biotechnology in
Things are going to change in the way we talk to each other and the way we share knowledge, and the way we use funding. With crowdsourcing you could, you could actually use a lot of energies in country like the U.S., which is pretty crazy. So it's a question of education at the level of those young generation to include them in this innovation journey. You don't want to leave, you know, people at the margins of this change. And I think by showing them how much of a revolution it is, in the mindset, like I was saying for cancer research. I mean, You know, some researchers they work on T-Cells and made a lot of progress very quickly by showing those things and by getting this new generation in the move; I think we can go much further. But do not forget the anticipation; we are really bad at anticipating in different cultures. In the
[applause]
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