Sunday, 24/9/2017 | 7:07 UTC+0

How to create a new life form: Historian Sophia Roosth on the future of synthetic biology

The field of synthetic biology, or engineering new forms of life, is less than two decades old, but its pioneers are responsible for some of the most interesting projects coming out of labs today: inscribing lines of James Joyce onto a synthetic genome, reproducing the smell of a rose without actually needing a rose, and possibly bringing back the extinct woolly mammoth.

So how did this field get started? Where do synthetic creatures belong on the family tree? And how does the language we use when we describe synthetic biology shape the field? The Verge spoke with Sophia Roosth, a historian of science at Harvard University who spent years studying the culture of synthetic biology for her new book, Synthetic: How Life is Made.

This interview has been edited and condensed for clarity.

The grand ideas of synthetic biology — like bringing back the woolly mammoth — seem very far away. But oftentimes I find that ideas that seem futuristic are already around us, like having a cochlear implant or an IUD technically can make you a cyborg. Are there any examples like this for synthetic biology?

Right, a lot of people think of synthetic biology as something very futuristic. That’s common because a lot of science talks in terms of future promises. You can’t write a grant application to the NIH without using that rhetoric: step 1, get the grant; step 2, do my research; step 3, cure cancer.

But on a more simple kind of day-to-day example, there are already some parts that have begun to influence the world in small ways. I think many people aren’t aware of the kinds of synthetic entities that they’re interacting with on a daily basis. One example is the HPV vaccine, which is synthetically produced.

The scientist Jay Keasling, for example, is working to develop a synthetic anti-malarial, which is orders of magnitude cheaper than any kind of naturally produced anti-malarial. Over at Gingko Bioworks, they’re working on synthetic flavoring and perfumes, which is one of the places where synthetic biology does overlap quite a bit with biotechnology to porting genes from one to another to create certain kinds of qualities and capabilities.

When people are creating new synthetic organisms, how will they fit in our existing family trees? Are there going to be new trees?

A question I heard voiced by scientists in the lab is, “What kind of entity is this? What does it mean to have these new forms of life that contain genes from really diverse lineages?”

This is a concern shared by both the scientists themselves and the social scientists thinking about the issue. There’s no consensus, but I think one of the ways it’s been answered is the idea that, actually, the fact that there are organisms that contain multiple lineages is not new. This is something that’s very common for microbiome research. We’re full of bacteria and there’s viral DNA within our own DNA, and fungi are growing in various parts of our body.

So there are other examples of that, so-called meta-organisms that contain different kinds of life from diverse lineages. And then a lot of scientists will point to that to say, when we’re thinking about what constitutes an organism, maybe a single genome is no longer a meaningful way of defining what a species is anyway.

What do synthetic biologists think about evolution?

It’s really varied. Some synthetic biologists would say evolution was the greatest tool they had in their toolkit. Unlike other engineers, they were working with a material that could actually modify itself.

Others would say it was its greatest design flaw because it creates organisms that, over time, are full of these capabilities that are no longer necessary but are a product of evolution. Some say this is a form of forward evolution and they weren’t doing anything that evolution wouldn’t do on its own, we’re just doing it faster. And some say that actually what synthetic biology is up to is kind of wresting life away from evolution, that evolution had controlled the kinds of things that life looked like for too long and that synthetic biologists could intervene and shape life in a more human-oriented way.

Let’s go back and talk about history a bit. Synthetic biology really is the cutting edge of science, and it’s only been around since the early 2000s. How did that happen? What was the leap that first made someone think, hey, we can engineer new forms of life?

Drew Endy at MIT was trying to create a computational model for a very simple bacteriophage called T7, which has been studied in microbiology labs since the ‘40s. It’s an incredibly well-known and very simple organism, and his thinking was that it should be relatively simple to predictively model. It can only do two things: either sit inside a cell, or replicate — burst the cell and infect more cells.

What Endy found is that this is actually incredibly difficult. You can’t predictively model any of this behavior on the computer. But instead of scrapping the model and starting from scratch computationally, he thought, well, if the phage which is so simple is still so complex that we can’t understand how it works, then we should be able to build a simpler phage that is predictable. And then the further thinking is, if you can make a phage that is viable and predictive, maybe you will actually know more about the virus than you did beforehand.

In the early days of the field, was there a goal that scientists were working toward? I don’t expect an explicit manifesto, but what did they see as the purpose of synthetic biology?

The early motto of the MIT Synthetic Biology Working Group was “making life better one part at a time.” What counted as “better” was a big question to be answered, but it was partly about design principles. It was about the challenge of whether we could make life that would adhere to certain kinds of engineering principles that you wouldn’t find naturally.

Sophia Roosth. Photo by Annette Hornischer

You spent years interviewing synthetic biologists and studying their culture. What assumptions did you have about the field before going in? Were there any surprises?

One of my guesses was that synthetic biology was part of biotech, and doing similar stuff to what biotech has been up to since 1973. And what I found most interesting once I started working in the lab and learning more is that, while on the surface of things it looks like the research is quite similar in the kinds of techniques being used, the kinds of questions being asked were altogether different.

Biotech is invested in trying to create practical new biological entities: something marketable, something useful, like pharmaceuticals. In early days of synthetic biology, that’s not the case. It’s not about trying to find useful things, but really trying to build new biological objects.

Let’s talk a little bit about terms here. Your book has an entire section about the language used in synthetic biology. What does the language we use around the concept of “synthetic” tell us about synthetic biology?

Language is so important. Synthetic biologists refer to different parts of the genome as “circuitry” or “on-off” switches, and that’s beholden to a much longer history of electrical engineering and computer science. I’ve heard so many times people talk about, “What’s the difference between programming a cell and programming a computer?”

Interestingly, [science historian] Lily Kay says that the description of genetic material of “code” actually preceded association of “code” with computers. It used to be associated with ideas from linguistics before it became associated with computers.

But what are the actual effects here? If we used different terms to talk about synthetic biology, how would things be different?

Language has effects on the way we imagine how biology works. If you think about life as a machine, that is going to get embedded in the way you approach problems of biological design and biological engineering. Take reductionism, or the belief that you can explain the whole by reference to the function of each of the ways. There’s been pushback recently in fields like systems biology, but it’s overwhelmingly common in much of biotech and synthetic biology. It’s the belief that if you know what all the parts do, you’ll be able to say something about the whole, and so the focus is on parts. That language of reductionism, of machine parts, affects the design and the way you approach things.

It’s also very common to talk about whether people were creating life and whether that was a “godlike” process. During the debates about creationism and controversies over teaching evolution in schools, there was an interesting contingent of intelligent design proponents who said that synthetic biology was a demonstration of creationism. If it takes scientists at MIT and Caltech years to make something as simple as a virus, there’s no way this could have happened naturally, right? Synthetic biologists found this funny at best and something to be concerned about more often, but it also shaped the ways they talked about what they did. Synthetic biologists I was working with at MIT stopped using the word “create” because it was just too inflammatory in the political contexts in which they were working.

What do you think is next for the field?

Synthetic biology is beginning to turn into something that’s less of a discipline in itself and more of a commonsense approach to bioengineering. It’ll become both less surprising and more thinly spread across the life sciences.

The closer biotech gets to modifying humans, the more ethical concerns will attend it. But let’s take a prior example like recombinant DNA. In 1973, people were concerned that scientists were playing God, concerned with ethical issues and issues of public safety. Now I have a sister who’s a freshman in college and she called me to talk about how she’s doing some basic recombinant DNA in her lab class. It’s the kind of thing that has become ubiquitous and unremarkable.

My guess is that both the methods and the technology of synthetic biology — and here I’m thinking particularly of DNA synthesis — will continue to become more common, less remarked upon, and just part of the toolkit of biotechnology and bioengineering.

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