ETech Preview: Creating Biological Legos

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If you’ve gotten tired of hacking firewalls or cloud computing, maybe it’s time to try your hand with DNA. That’s what Reshma Shetty is doing with her Doctorate in Biological Engineering from MIT. Apart from her crowning achievement of getting bacteria to smell like mint and bananas, she’s also active in the developing field of synthetic biology and has recently helped found a company called Gingko BioWorks which is developing enabling technologies to allow for rapid prototyping of biological systems. She will be giving a talk entitled Real Hackers Program DNA at O’Reilly’s Emerging Technology Conference, March 9-12, in San Jose, California. And she’s joining us here today. Thank you for taking the time.

RESHMA SHETTY: No problem. Happy to be here.

JAMES TURNER: So first of all, how do you make bacteria smell nice, and why? I get an image of a commercial, “Mary may have necrotizing fasciitis, but at least her hospital room smells minty fresh.”

RS: Well, the original inspiration for the project was the fact that for anybody who works in a lab, who works with E. coli, when you grow cultures of the stuff, it just smells really bad. It smells really stinky, basically. And so our thought was, “Hey, why don’t we reengineer the smell of E. coli? It’ll make the lab smell minty fresh, and it’s also a fun project that gets people, who maybe aren’t normally excited about biology, interested in it because it’s a very tangible thing. I can smell the change I made to this bacteria.”

JT: So what was the actual process involved?

RS: So the process was, you basically take a gene, we took a gene from the petunia plant, which normally provides an odor to the flower, and you place that gene into the E. coli cell. And by supplying the cell with an appropriate precursor, you make this minty smell as a result. So it’s fairly straightforward.

JT: Your degree, biological engineering, is a new one to me. How is it different from biochemistry or microbiology or genomics or any of the other traditional biotech degrees?

RS: Well, biology and biochemistry, and so on, are concerned with studying the natural world. So I’m going to go out and figure out how the natural world works. Biological engineering, instead, is really all about saying, “Hey, we have this natural world around us. Biology is, in some sense, a new technology through which we can build new engineered biological systems.” Right? So the idea is, what’s the difference between physics and electrical engineering? Electrical engineers want to go build. So in biological engineering, we’re interested in going and building stuff, too. But using biology, rather than physics, as the underlying science of it.

JT: Explain a little bit about the field of synthetic biology.

RS: So synthetic biology is a new field that’s developed over the past few years among a group of engineers and scientist all over the world who are saying, “Huh, you know, right now it’s really actually quite hard to engineer biological systems. Even just to put pieces of DNA together can be a fairly laborious and manual process that’s pretty error-prone. So how do we make that process easier? How do we make it so that an undergraduate or a team of undergraduates can go engineer E. coli to smell like wintergreen and banana in just a summer?” Typically, people usually assume that those types of projects are just too hard to do, because the tools we have essentially suck. So synthetic biology is focused on the effort of making biological engineering easier.

JT: What areas do you see synthetic biology having the largest short-term impact on?

RS: Well, I think you’re already seeing some of the impacts in, for example, the biofuel space. So there are a lot of folks interested in saying, “Hey, instead of pulling oil out of the ground, why don’t we just make it from a vat of engineered microbes?” And the project that’s the most intriguing to folks right now probably is a company called Amyris Biotechnologies, where they have a pathway for making an antimalarial drug. This is a drug that you can naturally find and extract from the wormwood plant, but these plants are pretty rare. And it’s really expensive to manufacture this drug from the plant. And so, in order to develop more cures, or essentially develop more of this drug and get the cost down cheap enough so that it’s actually an accessible cure for malaria for use in third world developing countries, they engineered microbes to produce the antimalarial drug. And so this is the poster child application of synthetic biology; by making stuff cheaper, you can essentially better people’s lives.

JT: A concern that some people raise about the ease of which one can order designer biology these days is that it’s becoming more likely, either by accident or design, for something particularly nasty to enter the environment. What’s your take on that?

RS: Well, for us, what we’re really interested in doing at Gingko is making biological engineering easier. And obviously, one of the aspects of what that means is you’re essentially democratizing access to the technology. You’re making it so that more and more people can come in and engineer biological systems. Now just like with any technology, by making it easier and making it more accessible, you’re both promoting huge advantages, and there are going to be areas for concern.

How do we know that the next time around when we have an outbreak of Avian flu, or whatnot, how do we know that the traditional “academic” labs and research institutes around the world are going to be prepared to respond? Maybe we can develop a wider network of people who can work towards engineering biological systems for good. You’re creating a larger community of people, that you can tap into to come up with useful things for society. So from our perspective, yes, we are making biology easier and we’re democratizing access to it, but we’re also working to make that community of folks who are doing this work as constructive as possible, and trying to create a culture essentially where people are trying to use these technologies for good rather than for harm.

JT: I guess my concern is that if you look at the history of computers and software engineering, the easier it gets to design things, and especially when you look at things like computer viruses, it’s gotten to the point now where essentially, there are the equivalent of these “send us a sequence and we’ll give you DNA [companies].” There’s “send us what you want your computer virus to do and we’ll send you back a computer virus.” I’m just a little concerned that the track record of humanity, when given easy access to new technologies, has not been great.

RS: Well, what’s the alternative to what you’re suggesting? Should we all get rid of our computers so that we don’t have the potential for computer viruses? You have to understand that, yes; there were some costs that came about with the computer revolution. But there were also huge benefits. You’re giving people access to information in a way that they never had before. So, in some ways, you can think about it that computers save people’s lives. If I have a rare disease and my doctor doesn’t happen to know how to diagnose it, I can go Google online and look for my symptoms, and potentially find the right doctor to go to to help cure myself, right?

So, the problem with every technology is that you have to take the bad with the good. So what we can do, basically, is to try to bias the technology into folks who are working around that technology towards good as much as possible. And that’s what I and others are actively working to do. So your question is — you’re ignoring all the good that has come out of things like making software programming easier and more open.

JT: The point’s well taken. One last question on the subject and then we’ll move on. My wife has told me — she took organic chemistry in college, and was told that basically once you have a degree like that, expect that the government’s going to keep an eye on you later on in life, if you’re ordering things, for example. Has there been any thought or talk about, for example, Homeland Security keeping an eye on what’s going on in this field?

RS: Well, I would say that the relationships have been actually much more positive than that. I think the idea has been for researchers in the field, and for folks from government, and folks from industry, to get together and figure out, “Hey, there’s a lot of good that can come out of this. But there is also some potential for accidents and harm. How do we work together to create an environment where the most constructive things happen?” So I would say that there has certainly been discussions with folks from government. But it’s not so much been a “how do we tamp down on this or how do we regulate this”, but “how do we work together to minimize the risk of something bad happening.”

JT: So changing topics, are kids who are entering secondary schools today prepared for a career in biotech? And what would you like to see change in the way biology is taught?

RS: Well, there’s a lot that can be said about the US education system, especially when it comes to science. But I would say that the coolest thing about synthetic biology is that it’s a very creative process, right? People get to go in and think about, “Hmm, if I wanted to design a biological system, what could I go build? Maybe I want to engineer E. coli that can take a bacterial photograph on a plate. Maybe I want to engineer E. coli to smell like wintergreen and bananas. Maybe I want to engineer a system that can detect arsenic contamination in well water so that folks in Bangladesh can test whether their wells are contaminated.”

There’s a huge potential for creativity. And so one of the things that I love about synthetic biology and biological engineering is that there’s a huge capacity to inspire young people to be creative and to get into science. And I think we’re seeing a lot of that with young folks who are interested in synthetic biology and trying to figure out “how do I get into this?”

JT: Do you think that the teachers at that level are up to the challenge of assisting with this stuff? Or are the kids going to have to be Heinlein-esq, and go off on their own to do it?

RS: As with anything, I think there’s going to be a spread. There are teachers who are actively looking to how to integrate these types of educational materials into their curriculums. They’d love to be able to integrate these types of ideas. The way that the community is trying to foster that is basically by making a lot of the materials and the research and the work that goes on as open as possible.

So, for example, I was a founder of OpenWetWare.org. It’s a wiki, basically, where biological engineers and scientists can post information about their work. Folks in the synthetic biology community have really taken to that, and basically posted their ideas and their work and their protocols, and by making this information available, you make it so that teachers and educators from all around the world can basically reuse that material in their own teaching. I think, for enterprising teachers who want to make use of or who want to incorporate synthetic biology into the curriculums, there are avenues to that. We still need better materials, don’t get me wrong. But I think we’re trying to do all we can to make it easier for educators to teach about the field.

JT: Your company, Gingko BioWorks, and I’m quoting from your website here, is focused on improving biology as a substrate for engineering. When you take the market-speak away, what does that really mean in terms of products and services? And who do you see your major client base as?

RS: So what Gingko’s trying to do is make biology easier to engineer. All of the founders of Gingko are actually engineers from other fields. So I was a computer scientist. We have a chemical engineer, a mechanical engineer, an electrical engineer and another computer scientist as among our founders. So the way we think about biology and engineering biology is, we think about it in terms of the design cycle. I want to be able to design a biological system. Then I want to be able to build it. And then I want to be able to test and see whether it worked. And I want to go around that loop as fast as possible.

So what Gingko’s trying to do is initially focus on the construction step. To say, “Hmm, if I want to build a biological system, I need a set of parts. Essentially, I need my Legos which I can mix and match in order to build my engineered biological system. So I need my part set and I need a way to assemble those parts as quickly as possible into different biological systems so I can see which one works.” We think of it as essentially a platform for rapid prototyping of biological systems. And so that’s what Gingko is doing right now is developing the parts set and developing the technology for rapidly assembling parts into systems.

JT: So if I, or your typical Make magazine reader, said, “Gee, I’d like to go try this stuff out,” what kind of a setup do you need these days? Is it something that somebody with a few hundred dollars and the inspiration and a basic background could go set up? Or are you still talking about a lab full of glassware to do this?

RS: Well, it depends on exactly what the person wants to do. I think some basic experiments can be done pretty cheaply with an enterprising person using EBay and whatnot. But the thing I should point out is that in terms of do-it-yourself biology, or amateur biological engineering, there are regulations in certain places in this country in terms of doing genetic engineering. Such as taking DNA from one organism and putting it into another. So you would need, essentially, a lab facility to do some of the work, according to federal regulations. The situation’s not entirely clear, but I would say as a word of caution, there are some regulations in place that you should think about following if you’re interested in this type of thing as an amateur.

JT: So I guess what we need is the equivalent of a place where you can go when you’re repairing your car, that has the lift and everything.

RS: Exactly. Yeah. So there are lots of folks who are interested in developing essentially the equivalent of hacker spaces or community labs, where people can come together and think about how to have the right tools and equipment for engineering biological systems. So there’s a group in Cambridge here that’s already working on that problem.

JT: So you can go and say, “Charlie, could I borrow a cup of restriction enzymes?”

RS: Exactly.

JT: So can you give us an idea of what we can expect to hear at your ETech talk?

RS: Well, at ETech what we’re really looking forward to doing is chatting with folks about the technology and possibilities, as well as giving people an idea of what’s possible. So we’re going to do a little demo with some folks, where they get to probably engineer some bacteria to turn red, is what we’re going to try to do. So give people some idea of what’s involved in biological engineering.

JT: It sounds like it’s going to be a lot of fun. So it’s going to be a very hands-on type of thing it sounds like?

RS: Yeah. Yeah. just listening to people talk can be a bit boring, so we want to give people a chance to play a little bit.

JT: All right. Well, I’ve been talking to Reshma Shetty who is one of the founders of Gingko BioWorks. She’ll be speaking at O’Reilly’s Emerging Technologies Conference in March, speaking on Real Hackers Program DNA. Thank you so much for talking to us.

RS: Thank you. It was a pleasure.

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