The Dutch Rathenau Instituut started in 1986 as a technology assessment center to advise Dutch Parliament. It has since developed into a broader think tank studying the organization and development of science systems, while regularly publishing and stimulating debate about the social impact of new technologies. Volume talks to the Institute’s Rinie van Est and Virgil Rerimassie to hear about the main trends in synthetic biology and related disciplines. They paint a picture of the world where biology and technology have converged, and where our fundamental way of working through scientific problems has shifted.
Brendan Cormier: Rachel Armstrong has a piece in this issue that explores how we define synthetic biology. She states there are two fundamental views: a gene-centric view and a chemistry-centric one. How do you define it?
Virgil Rerimassie: There are a lot of definitions being employed; maybe I can use an example to make it more clear. If you look at classic bioengineering it’s about having an organism that you want to modify by using something from another organism. Through bioengineering you can cut something out of that second organism and paste it into the first. If you look at synthetic biology, it’s not about what you want to modify, but what you want to design: what do you want this organism to be able to do? We’ve been able to map the whole software code of life. So now it’s about taking an organism, stripping it of everything you don’t need and then inserting elements from multiple different sources. So we’re moving from having organisms that we basically already know to making organisms that haven’t yet existed in nature. The whole idea is to be able to design micro-organisms that can perform useful tasks. That is the core of synthetic biology. In addition, synthetic biologists are able to use synthetic DNA, because essentially it’s a molecule that you can produce without having to retrieve it from nature. Before, bio-engineers had to cut and paste the A, C, T and G sequence from DNA out of an original organism and then paste it into another organism, but now we have a kind of digital version. For example the gene responsible for giving light to a firefly, that green luminescence, we know the software code of this particular gene, so you don’t have to cut it out of a firefly anymore. You can just look that code up and order it from a specialized company.
BC: So to follow the computer metaphor, you’re learning batch codes, the batch code for luminescence, rather than literally building new code from the basic A,C,T, and G of DNA?
VR: Yes, but that coding from the basics is something they’re working on too. Nature hasn’t yet used all the DNA sequences that are mathematically possible. So there is a lot going on in computing, trying to predict what kind of sequences might lead to what functions. It’s still mostly about recombining what already exists, but those recombinations could lead to new properties and abilities within organisms.
Rinie van Est: Since the seventies we’ve had the technology to genetically modify living organisms; synthetic biology on the one hand is just extreme genetic modification. But if you take it one step further – and that is a giant step – biology is no longer the substrate we’re building on; instead we’ll use technology as a substrate. That is exactly what synthetic biology is in part about. We had this big project ‘Making Perfect Life: Bioengineering in the Twenty-first Century’, that we did with a consortium for the European Parliament. We looked at the convergence of four key technologies: nanotechnology, biotechnology, information technology, and cognitive sciences (NBIC). This NBIC convergence actually means that life sciences and physical sciences are merging. Life sciences originally researched living organisms and the physical sciences dead materials. But because they are merging, these boundaries are blurring. And that leads to two mega-transitions in engineering. The first is biology becoming technology. We’ve been talking about this for the last thirty years. In the Netherlands we had Herman: the first genetically modified bull with a human gene in it. In the nineties we had discussions about GM foods, we had the cloning of Dolly, all these topics. The second transition is technology becoming biology. This is as a trend that is just now becoming visible. Artificial intelligence has been around since the fifties, but in the last ten years we’ve been getting more technology with characteristics similar to living organisms: notions of self-repairing materials and intelligence in robotics, for example. We looked in a very broad way at four areas of bioengineering: engineering the body, the brain, intelligent objects, and living artifacts. The latter basically refers to the field of synthetic biology. So to understand what is happening in these fields of science and technology, you have to be aware of both trends. As Virgil mentioned one institute was able to build the whole genome of a bacteria; they had a kind of ‘empty bacteria’ – that is the way they speak about it. But the substrate is still an existing living organism. I call this top-down synthetic biology. At the same time there are also bottom-up attempts at synthetic biology, building protocells from scratch. So in addition to the extreme engineering of existing organisms, there is this ambition to model and physically build living organisms from scratch. You see that in all four of these areas of bioengineering. If you look at the brain, you have new interventions, like deep brain stimulation (DBS). DBS is a way to treat, for example, someone with Parkinsons, to reduce tremors. At the same time DBS is becoming a research tool. For example, we treat tremors, but notice the patient becomes a happier person. It’s a side effect, but it’s also a research result and will have an impact on how we will use these technologies in the future. That is the top-down approach with the brain as the substrate. But in the Blue Brain Project, scientists try to rebuild and model the brain on a molecular level. This is bio-mimetics: creating an artifact, which, if it works, becomes a supercomputer. And maybe this tool will help us really understand the brain.
Arjen Oosterman: You’re outsmarting The Matrix.
RvE: What I see is that these types of development really change the way we look at both nature and technology. I see these things happening on a wide scale, not only in emerging technologies, but also in discussions of nature conservation.
AO: Can you give an example?
RvE: Take climate change, it took a long time before we accepted it as an issue. Then the first reaction was mitigation. Then at the end of the nineties we saw that mitigation wasn’t working, so our alternative strategy was adaptation: accept that the climate is changing, maybe not totally, and then adapt to that system. What you see now is people worried that adaptation won’t work. So you get geo-engineering and climate engineering. Not combating CO2 production, but actively removing it from the air. You might be able to reduce levels to what they were before the industrial age. It’s a different way of looking at the climate system, at the problem.
AO: Yes, but in the past there still was this worry that if you meddle with nature, the whole system could fall apart. The debate on gen-tech is basically about that I think. Now it seems that you are suggesting we might be moving out of this paradigm of an interdependent system called nature towards creating a self-sustaining system of its own, based on different conditions.
VR: That’s an interesting thought. I think it goes both ways. Some synthetic biologists express a deep respect for nature and they are modest; that their work is just a tool that we can employ in order to make bio-fuels or medicine. Other people say: now if you look at nature it actually did quite a silly job, because it’s quite fragile and it could have been done better, more efficiently. In terms of designing total eco-systems, that’s one of the issues bioengineers have been struggling with, because it’s one of the classic arguments against bioengineering and biotechnology; that these new organisms will get into nature and start to mutate and take over and so on.
BC: Can we view synthetic biology as adding a kind of subjectivity to evolution? So evolution itself is a kind of an objective rule-based process, but by adding decisions made by the humans, you are adding the whims and emotions of the human mind to the whole objective evolutionary process.
VR: If we let a synthetic biologist do the talking, someone like Craig Venter, he’s not afraid to say that his cell with a synthetic genome is the first organism whose parents are computers. And this is something new, this was never out there, so in that sense I can agree with you. There’s also this idea of XNA instead of DNA. X says ‘unknown’; so far four letters have been used as possible DNA. But there are different molecules in nature that could be used as DNA. So you’re replacing one of the letters and get XNA. It goes back to the idea of engineering for useful purposes. It’s not about creating artificial life per se, but about having the ultimate safety tool. If you have an organism that uses a different programming language then you have a built-in safety, because it won’t match with other organisms. The threat of mutation and things getting out of control becomes impossible, at least that’s the idea.
AO: But if we look at this idea of nature being in trouble due to human intervention or human existence, there are two responses. One is to back off; try to keep nature as natural as possible and reduce our impact. The other is to compensate; design compensation for what we do to nature.
RvE: You definitely see on the one hand synthetic biologists saying: we are not trying to play God, we’re just trying to use what nature has given us for useful purposes. Others say that if you look at nature, the way it works is quite flimsy actually. We see that we can actually redesign pieces in nature and do a better job. They go even further and say: the Dodo is extinct and we as humans are guilty for its disappearance, but we might be able to put it back on Earth. Isn’t that a moral obligation for us now that these technologies are becoming available? We have found out that the Dodo is genetically quite similar to the pigeon and you could strip the parts of the pigeon that do not resemble the Dodo, you can compensate the genetic makeup of the Dodo by using synthetic DNA. So you can use synthetic biology to compensate for the negative impact humans have had on other species.
BC: Maybe on a more immediate level, let’s say that panda bears are dying out. Are we comfortable with engineering a better panda, that can survive, that doesn’t suffer from existing conditions? Or do we say, evolution is king and the panda has to die out? This is a fundamental dilemma.
VR: Definitely. And if you’re talking about evolution being king, and whether or not synthetic biology might challenge this idea of the panda dying out, why worry? Because we are able to resurrect extinct species or clone them, so what’s the issue? The idea of making a panda 2.0 is interesting, but it goes a bit beyond that as well.
BC: But you, as somebody who answers to the government, how would you begin to respond to that question? Do you have a system for evaluating these scenarios?
RvE: For starters we would ask the stakeholders for their opinion. We would map that. We would refrain from giving our own perspectives.
AO: Ethics seems to be involved here. So how do you deal with ethics? Because ethics originally dealt with humans relationships, and then started to include larger animals, like horses and whales, and then smaller ones like apes, rats, and mice, but does this also extend to, for instance, bacteria? So how do you deal with ethics? Do you simply say: the opinion of fifty-seven percent of the population is so and so?
VR This goes to the heart of what we try to do. One of the key elements here is that we are politically neutral. Taking synthetic biology as an example: it’s a field where everyone has a feeling that there is something controversial going on. What we try to do here at the Rathenau is try to be preemptive. The Rathenau has to assess these developments quite early on. Since we have quite a clear view of what scientists are doing, and what their ambitions are, we can ask ourselves about what it all means at a higher level. What are the issues involved, the controversies that parliament or the public might stumble upon? Our job is to make sure these questions and issues are put on the table early on.
BC: When you have so many different scientific breakthroughs happening at different levels there seems to be a need for coordination, to coordinate the collective intelligence of scientists towards a set of goals. Is that something you see as something important in the future?
VR: I think this is crucial. The iGEM competition is a bioengineering competition for students. It grew from five teams in 2004 to a hundred and seventy teams from more than thirty countries last year. So we have a new generation of bioengineers. But behind iGEM there is a kind of idea. These boys and girls can only score points if they address, very explicitly, social aspects. So if they want to win, having a top design or new organism that can do exciting stuff is not good enough. You need to look to society and have a social mandate. We cooperate with them and organize debates. We’re all about stimulating debate on emerging issues and they are an organization that wants to bring their scientists into touch with social aspects and enhance debate as well. So in that sense it’s not about coordination, but there is a willingness and openness to really listen to each other.
AO: Now to the bigger picture, what are the main trends and developments you see happening?
RvE: We see a shift from a mechanistic view of the world – this enlightenment idea that you look for the laws of nature – towards a more informational view on reality. For example the way we look at our body, the idea that if you can monitor it, if you have data, you can check that data with a specific goal. And based on data and your goal you can change your behavior or optimize the system. So instead of understanding how this body works, you’re just measuring it and creating data. That is a different way of trying to understand who I am. It’s a more of an engineering way of looking at things. You can try to understand the complexity of micro-organisms, but you’ll find the complexity is enormous and it’s hard to steer. An engineer would try to take it apart, minimize it, and then see, to what extent you can tinker with it. Or try to model it and then based on that model manipulate and build things. It is exactly this informational worldview that is driving the two big bioengineering trends mentioned before: biology becoming technology and vice versa.”
VR: “An interesting example of a different kind of control is the work of George Church with his team at Harvard. They developed this machine called MAGE (Multiplex Automated Genome Engineering). It’s a cloning device, but it’s not about cloning, it’s a kind of high-speed evolution machine. So you are able to use a certain bacteria and make a million different copies out of it. Then you select the nice ones. So you’re using the engineering power of nature itself, and then human rationality comes in to pick out the ones that you find interesting.
AO: Why do you include cognitive science in your NBIC convergence model? We haven’t discussed it so far.
RvE: Cognitive sciences in combination with information sciences contribute to the notion of artificial intelligence. At the beginning of this century, coming from the Human Genome Project, we saw that information technology and biotechnology were really merging. Biotechnology was seen as an information technology. In the seventies and eighties there was a convergence between information technology and mechanical technologies: megatronics – mechanics and electronics. And in the nineties you saw a convergence between information technology and communication technology: ICT and the internet. The next phase of convergence will be NBIC convergence, meaning that life itself is going to be digitized and synthetic biology is an example of that. But our social life is also being digitized, which is all a kind of cognitive process. In relation to this concept of NBIC convergence, a couple of years ago we started to look at emerging technologies that interfaced between these various key technologies. In 2007 synthetic biology was an important issue; the last couple of years we were mapping what is going on in cognitive science, but also in robotics, ambient intelligence, and persuasive technology. For us these are important areas to investigate.
AO: Persuasive technology?
RvE: That’s the idea of using information technology to influence behavior. For example you are driving a car and you get feedback about how much gasoline you’re using. Or with light, ambient lighting can influence the behavior of consumers or employers. One of the things we’re studying at the moment is e-coaching in the field of health. In all these fields you have this cybernetic thinking. You map behavior and try to give feedback, almost continuously. On a completely other level digital information changes our perception of the world. Kids for instance, who spend most of their time behind the screen, playing video games, when asked to play outside may find the nature they’re confronted with boring, because for them the real thing is what they see on BBC, National Geographic, or even virtual nature in games. That introduces a dynamic in which kids don’t want to go out, because it is framed as dull and not real nature. From an architectural point of view, that is a challenging notion.