Weekly Synbio Community Author Q&A: Drew Endy on Design for Life
An interview by Johanna Kieniewicz
Synthetic biology reworks, remixes and repurposes the stuff of life. Its creative potential is nearly limitless and if realised, has vast societal implications. Recently, we have seen a man-made DNA base pair added to a living organism, the emergence of DNA as an information storage device, and BioBricks—a visionary set of tools that aims to allow users to combine different biological parts á la. lego into new and different structures
A new book, Synthetic Aesthetics, is the product of an interdisciplinary dialogue and collaboration between scientists, engineers, designers, artists and sociologists. If biology is something that can be designed, what are the implications and what values will apply? What difficult questions will artists bring to the fore? And what possibilities might emerge when synthetic biology is placed in the hands of the designer? I caught up with Drew Endy, one of the co-authors of the book (and a Principle Investigator on the NSF/EPSRC- funded Synthetic Aesthetics project), and Associate Professor of Bioengineering at Stanford University, to explore…
A different way to think about biology
JK: Synthetic Aesthetics is very much about the future of synthetic biology. What is your vision for the future of this field?
DE: From a scientific perspective, synthetic biology is a complementary approach to learning about how natural systems work. We’ve had several generations of taking biology apart into molecules. With systems biology we’ve worked to put things back together conceptually as mathematical models and theory. Now, with synthetic biology we’re putting things back together and seeing what really happens. It’s a complementary approach of learning by building. Synthetic biology doesn’t replace taking things apart, it doesn’t replace theory and modelling, it’s a powerful complement.
So my expectation is that the science of biology will advance further and again by the addition of synthetic approaches. Meanwhile, to an engineer, living matter is the most impressive stuff on the planet; it’s a nanotechnology that actually works. All life on earth depends on it. So, from an engineering perspective, [living matter] is the nerd rapture. We have this ultimate manufacturing platform that’s capable of putting atoms where we would like them to be and it’s already taken over the planet. It’s running on 90 terawatts of energy via photosynthesis which is over four times the amount of energy that our civilisation consumes.
We’ve finally created a cultural critical mass to sustain incremental improvements in the design/build test cycle; we’ve had genetic engineering for one human generation going back 40 years, and the economic impacts of that are just getting started. With synthetic biology, we can celebrate not just the application of biotechnologies, but the incremental sustained improvements in the tools that we use to engineer living systems. So we’re going to make living matter as engineerable as possible. But, in this context, to what end and how does this relate to ourselves as humans? What values do we place on this technology?
That’s where Synthetic Aesthetics comes in. In part, Synthetic Aesthetics acts as a negative reaction to other framings of the future of biotechnology. In Britain for example, in getting synthetic biology going, the metaphor of industrialisation has been used. It’s not that I’m against industry, but when you use the metaphor of industrialisation, you have to take that literally and evaluate what that might lead to, and that’s been exploitation of natural resources, primarily fossil fuels, to create this amazing turbo boost of civilisation, but also creating a lot of natural damage.
So, how about we don’t do that with biology? If we’ve got 24% of the land capable of growing plants not yet under human cultivation, how about we don’t make it really boring by getting rid of all of what remains. Why? Well, we’re really horrible at coming up with molecular gizmos that provide useful functions for us engineers. But, in fact, we take the really useful ones from natural biodiversity. If you’re a shit-hot optogenetics guru, you’re getting your gizmos from the salt-loving bacteria or the photosynthetic bacteria. You’re not inventing those light-switching channels from scratch. If you’re me, and you like flipping DNA back and forth, there is no chance I’m designing recombinases from scratch.
So as a self -interested engineer of biology I have to be a frontline defender of natural biodiversity, otherwise I’m a moron. And so one of the things that Synthetic Aesthetics is a reaction against is this trope, this default path of industrialising life. That seems like a first-order disaster in nearly every way I can think about it. But it’s very, very powerful because we’re coming right out of the industrial age into the information age and if we’re not thoughtful, we’re just going to take forward 19th century ideology into a totally different time and planet.
From one perspective, Synthetic Aesthetics is literally meant to be a political doorstop that says “there’s a different way to think about the future of biotechnology” and you can’t shut that out.
The Role of Designers
JK: One thing that really struck me about Synthetic Aesthetics is that was that it’s not simply cheerleading synthetic biology but is actually reflective, and at times quite critical. Do you think reflecting on synthetic biology from a multitude of different viewpoints actually might affect its evolution as a field of study?
DE: Absolutely and I’d take that more strongly to say I think that this is the field. These are not people outside the field, the artists, the social scientists. These are synthetic biologists, these are people who are defining what the field is. To view synthetic biology as merely being the domain of scientists and engineers is a mistake of the first order. Can I ask a personal question of you? What kind of computer are you using?
JK: A macbook air
DE: That comes from a company called Apple. I have a question for you? Is Apple a technology company or a design company?
JK: It’s both really. Actually I’d argue foremost design.
DE: So I’d like to take what you asked as a question, amplifying that everyone in that book—the critic, the designer, the anthropologist–is a synthetic biologist. You don’t have to be a scientist or engineer; we are all synthetic biology together. And we can return to Apple as an example– this design company is the largest publicly traded company in the world. And why is that? They’re giving people things that they want with technology.
After the first generation of genetic engineering, how have we done in giving people things that they want with biotechnology? For a few things we’ve done ok, like some medicines. And pretty much everything else has been a disaster. Recombinant insulin, ok—but pretty much everything else is hidden. For example, there are fish from the cold waters of the Antarctic that have antifreeze proteins that allow them to thrive at sub-freezing temperatures.
And there are low-fat ice creams that don’t have enough fat content to keep the freeze/thaw cycles from growing big ice crystals that screw up the texture. By making recombinant antifreeze proteins and sprinkling them in, you have a smooth, low-fat ice cream. This is already on the market, but is not well known because it’s not branded on the front of the ice cream containers. So we’ve totally screwed up the design representation—we’re not giving people what they want, or if we are giving people things they should want, we’ve screwed that up too [by keeping these improvements hidden].
Synthetic Aesthetics is not just a defensive doorstop that’s keeping the future from being closed off. I suspect it’s the greatest innovation and economic opportunity within the space of future biotechnology, period. 
JK: I thought that designer Alexandra Daisy Ginsberg’s user-centric focus was very interesting. She is interested in all of the possibilities out there, not just simply finding a solution to a problem—but actually throwing the doors wide open actually asking what might be. Is that something you see as something people with that kind of perspective can bring to the field as synthetic biologists?
DE: I think you see examples of that type in the book itself. A team of students working in Cambridge, England are able to make living pigments. So that’s great, but what do you do with living pigments? What would people want with that? Well the designers pick up on that and say maybe this is a new way to do medical diagnostics, where instead of X-rays, colonoscopies, needles, what if we could engineer the biology to behave in ways we could easily understand for health conditions?
As a design exercise, they prototype a probiotic yoghurt that is powered by E. chromi. What comes out of you represents the disease state of your alimentary canal and tells you if you should go see a specialist. That sounds a lot better than a colonoscopy, and highlights the fact that medicine is often limited by our ability to get information into or out from a patient. New ways of doing that would be wonderful.
Not changing ourselves, so much as listening and learning about ourselves with a technology that everyone could afford, and could be running as a background process. Also in that design exercise, note they predicted the year that people would be ready for this product. Not the science and technology beginning to work, which is approximately right now. The year they put down for the Scatalog—the probiotic yoghurt, is 2049. That’s how long they think it will take to work through the diversity of issues associated with societal acceptance.
JK: Synthetic Aesthetics recently made an appearance at the Victoria and Albert Museum in London. Did you feel like the audience engaged with what you are trying to do and were inspired?
DE: It was challenging and interesting from a variety of perspectives, and most of this is really the genius of Alexandra Daisy Ginsberg. From one perspective if you look at the V&A, it’s exhibiting from the contemporary to the past, yet Synthetic Aesthetics was an experience of exhibiting from the contemporary heading into the future, and so independent of what the substrate is, what the content is, that’s a tremendous frame of reference shift. I was told that the V&A used to have science as well. And that left and went across the street, so it was a return to science in that sense, too. There were a lot of deep currents afoot, and in terms of the content, shocking to see things like bacterial pigments displayed on easels juxtaposed in a room with paintings hanging on the wall. And you take all this together and it becomes impossible not to imagine what people in the V&A will be experiencing in 500 years; to declare that they would not be exhibiting living artefacts is insane. I don’t know what everyone else got, but I got some things that I’d never seen so powerfully and simply presented.
JK: As I understand it, the so called bio-error and bio-terror are the greatest concerns cited for the field. But are things that just work fundamentally different from the way in which things do now, is that a big barrier? It’s one thing if you’re simply replacing like for like, but if you’re creating something that just does things in a fundamentally different way….
DE: Are you creating design replacements, in which the design difference to a customer is negligible, if not purposefully zero, versus establishing whole new product categories?
JK: And the latter seems much more interesting. Because perhaps in some ways, it might be interesting to have green jet fuel, but in ways those might be perpetuating problems we already have.
DE: You’ve got it. So if you look at the [Synthetic Aesthetics] chapter on the cheeses, I think the lesson for me is that in addition to the instructions I got from my parents—treat your body as a temple, you are what you eat– this exercise tells us that we eat what we are. One artefact of modernity is that we’ve separated ourselves from biology, even though we are of biology. And now all of a sudden you can’t hide from the fact that this separation of ourselves from the rest of life is totally artificial, synthetic, ironically. So what product categories would we be displacing, not just dropping in replacements, but displacing?
The idea that I like the best is to replace the supply chain of how perfume is distributed. I’d like to have a website called iFumes. You can go there and pay 99 cents to download the DNA sequences encoding particular biosynthetic pathways, you then build the DNA locally and transform your epidermal ecosystem so that you have living, dynamic, programmable scents and fragrances and perfuming becomes software basically. And that replaces the material supply chain based on centralised manufacturing of petro and plant chemicals, put in physical containers, shipped around the world. To get into duty free catalogues in airplanes, we’ll still need Brad Pitt doing the marketing campaign for Channel.
But we’ll have what is arguably a superior, more creative product, and the environmental costs will be much lower, because you’re not going to need centralised manufacturing followed by distributed shipping.
New ways of doing science, new ways of thinking
JK: One thing I find interesting recently is the emergence of DIY biologists. The London Hackspace actually has a wet biology lab in it where individual hackers, citizen scientists can actually regularly work. In your view, what is the potential of this movement in the context of synthetic biology?
DE: Imagine it’s 1950 and you’re asking someone working in IBM or the defense department who programs computers what the programming of computers will look like in 2010. Biotechnology in its initial genetic engineering era has been strongly coupled to research institutions, for good reasons. One of those is concerns around safety and leveraging the capacity of institutions to manage liability and therefore have a framework through which to implement biosafety review programs. So I think that a lot of people, professional researchers, professional scientists look at DIYbio, and I think appropriately have two reactions. First, this is not serious science. Second, this puts the social contract at risk because it is beyond institutional oversight, to a degree.
But here’s the flipside. We human beings come from a planet with all sorts of problems. Part of what we do is we make things. The tools of genetic engineering are actually a generation old. There is now a second genetic engineering generation coming of age. It would be foolish to assume they will inherit all the perspectives, wisdom and baggage of the first genetic engineering generation. And it would be foolish to assume that they will be part of the institutions that rose up a generation ago. My expectation is that within a generation, there will be free-to-use languages for programming life. They will be accessible to anyone with an internet connection. Individuals and groups will be able to design, build, and test living systems comprising hundreds to thousands of genes. Innovation, mapping the needs and struggles of the world to the capacity of the technology, will not be limited by knowledge or tools so much as creativity. The limitation will primarily be understanding of what could be done that’s useful with biological technology.
JK: There seems to be a tension between the things that will enable such open innovation environments, versus patenting regimes that encourage investment. What is your reading of the situation?
DE: It’s a wonderful opportunity. In the US, one of the things we’ve lost is a connection between values and property rights. So if you go and read the US constitution in the section where patents are included, patents are the original attempt at open source. They are trying to do better and replace what was happening previously, which was trade secrets, which was not in the common good. And when confronted with this, the government developed a tool—and property rights are a type of technology — a tool for scaling transactions. A tool to incentivise you to share your know-how, to share your trade. A little give and get. Somehow, a couple hundred years later, we’ve lost that coupling of values to technology—and by values I don’t mean economic value, I mean moral value.
Meanwhile, I’m a nerd and I like things that make it easier for me to nerd out. I’d like to live in a world where I have a language for programming life. And what’s a language? A language typically has a dictionary of functions that are associated with doing things. And it has a grammar, rules of composition. So I need a dictionary of genetically encoded functions and I need a grammar for composing them in ways that behave as expected, or are at least amusing. That’s not too hard, but we’ll need lots and lots of people to help out. Second thing: we have a lot of experience with language. We have a whole set of languages for communicating, human to human. How much is it costing us to use this particular language of English right now? It’s really just the cost of learning the language. I don’t need to pay to use any of the words. All of these words that we’re using are free to use.
We also have other types of languages, languages that allow us to communicate with non-human systems: Java, C++, Python are all examples of languages for taking human ideas and translating them into electrical computing machines. How much does it cost to use those languages? Interestingly, initially it cost quite a lot to use them, because someone was charging quite a bit to use something that they made for the first time. But now we’ve only had a couple of decades working with electrical computers and their machine programming languages, and already 12 out of the 15 most used computer programming languages are free to use. I have a hypothesis: successful languages are under positive selection to become free to use. Otherwise they die.
So, as an optimistic technologist, I use the tool of “living in the future.” What is the future I want to be living in? I’ll need a dictionary for programming life, that’s a dictionary of words, functions, rules of composition, And it’ll be free to use because the empirical evidence suggests that languages are under positive selection to become free to use. This means we’d better start putting in place the mechanisms to get us there. I have two other things which are strategic advantages. First, I can be very patient. I don’t have to report a profit to my shareholders next quarter. If it takes 30 years, that’s great. That’s actually pretty fast. Second, people make the mistake of invoking an “exclusive OR” strategy as opposed to a simple “OR.” So they say, it’s either patents or not patents. That’s an “exclusive OR” strategy. Patents or Not Patents. A simple “OR” says it’s one or the other, or both together. Both together likely works best.
JK: You have started to work with San Francisco artist, Phil Ross, who is doing interesting things with wood fungus. Has that affected the way you think about your own science?
DE: Yeah. I think his work gives standing to the question — what is the state of the world, and what is it that we need and want? — in a way that goes way beyond health and medicine, which are oftentimes quite dominant in biotech. And, can I acknowledge my capacity to understand these other things? Though I may be an OK researcher, I may be totally clueless when it comes to understanding other people and cultures. So how about we just start with that as an open possibility. People who might be open to other lines of questioning and other types of research.
Additionally, I think at a much more detailed level, I have become less dogmatic about how I think molecules and cells must be engineered to work in a particular way. I have become much more focused on designing the questions and being agnostic about how the solutions might be realised. So the engagement with the design community and artists has allowed me to more directly see the blinders associated with technical or scientific dogma and to escape them while still basically being free to ask better forms of questions.
For example, in the BioBricks programme, we’d like to make parts that go together and behave as expected and we had all sorts of metaphors for how this might work based on experience with engineering other types of materials. Yet we weren’t really getting very far. We could standardise materials for assembling DNA, but how do you design functions within DNA such that composite objects behaves as you expect with high reliability?
We were flailing on that, and it became a poster child for the possibility of never getting BioBrick parts to work really well. The answer was to listen to nature. Find examples where such genetic architectures had been solved. We weren’t looking for the answer in the right way before, and the solution is a much more complicated genetic architecture [than we expected…].
The significance of being associated with Synthetic Aesthetics is that instead of being dogmatic with respect to the form of the solution ahead of time, our dogma became only associated with what we wished for; focusing our attention on our wishes as humans—what is it that we want? And then get out of the way with respect to how we find a solution.
JK: If you ask the right question, then the solution will emerge?
DE: And that’s quite well known in science. But what happens through Synthetic Aesthetics, through bringing in artists and designers, you have a powerful way to test and reframe your questions. Maybe that’s a way of noting it and making connections with things that other scientists will be familiar with. Are you asking the right questions? Here’s a new approach for upgrading your questions.
If you have questions or comments for Drew Endy about his research, methods, recent collaborations or views expressed in this interview, please use the comment form below this article to share your thoughts with the PLOS Synbio Community. Drew has agreed to respond here as his time permits over the next days and weeks.
Johanna Kieniewicz writes At the Interface on The PLOS BLOGS Network. She has a PhD in Earth and Planetary Science, a foundation degree in fine art. She is passionate about art and science and relishes her job in science at one of the world’s great cultural institutions, The British Library.