What exactly is synthetic biology?

What Exactly Is Synthetic Biology? It’s Complicated.

What Exactly Is Synthetic Biology? It’s Complicated.

The citizen’s guide to the future.
April 3 2017 7:14 AM
FROM SLATE, NEW AMERICA, AND ASU

What Exactly Is Synthetic Biology?

It’s complicated.

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Scientists have tried to produce glowing plants through synthetic biology. It’s not easy.

Photo illustration by Slate. Photo by iStock.

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So, apparently scientists are working to synthesize the genome of yeast? Is this, like, the first step toward better bread or something?

Maybe! But in the short term, they’re doing it in the service of synthetic biology more generally. It’s a discipline that brings together the insights and methodologies of computer science; engineering; and, of course, biology. It encompasses genetic engineering, pharmaceutical manufacturing, and molecular chemistry. But, in practice, it involves futzing about with the fundamental building blocks of life itself: reworking DNA—sometimes even writing it from scratch—and other molecular processes to engender new applications. And yes, if you believe its most ardent evangelists, it might help us set up shop on Mars, resurrect the woolly mammoth, and stop global warming.

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If we want to get really basic, the field (if that’s even the right term for this diverse set of inquiries and methodologies) has two main goals at the moment. First and most prominently, scientists are working to build new life forms, assembling them from their fundamental chemical components. Second, they are trying to use biotechnology to produce substances that are difficult to obtain by other means—medicines and fuels, in particular.

How is any of this remotely possible?

At its core, it’s all about the selective assembly of genetic information. This is where the connection with computer science comes into play. Synthetic biologists aren’t just copying and pasting existing DNA from one place to another—they’re looking to figure out how specific sequences work and then putting them together into new configurations. The idea is that you can figure out what given segments of DNA do and then patch them together, much as you would with lines of computer code, effectively programming cells to behave in new ways.

Those basic DNA components are sometimes described as BioBricks. Researchers maintain a database of these components, known as the Registry of Standard Biological Parts, that contains thousands of items. Today, it’s possible to synthesize such sequences from scratch and order them freely online. For instance, award-winning student competitors in the International Genetically Engineered Machine competition have drawn on these components to enable projects that involved printing tissue, keeping fruit fresh, and protecting bees.

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Can anybody can just put this stuff together and make whatever she wants? Can I just order up some bespoke DNA and go to crazy in my garage this weekend?

In theory, there are all sorts of things you could build from BioBrick components, but in practice it’s hard to get results easily. As Roberta Kwok explains in Nature, many of the components in the BioBrick registry are unreliable: Even if they worked in one context under specific conditions, there’s no real guarantee that they’ll work consistently in others. Ultimately, Kwok suggests, the Lego comparison may be inapt, partly because parts don’t always fit together well in cells and may integrate into them in unpredictable ways.

Researchers are also embracing CRISPR gene editing technology to build larger and more complex genetic circuits. But complexity brings its own challenges, potentially adding new layers of uncertainty. That’s one of the reasons that some synthetic biologists are working to create new life forms from scratch. If you can simplify the organism to the point where you can predict its behavior more consistently, you can potentially do a lot more with it.

Creating a life form from scratch? Has anyone actually pulled that off?

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Yes, actually! The J. Craig Venter Institute did just that in 2010, producing a single-celled organism with a synthetic genome. In that case, Venter’s team was copying the genetic material into an existing shell. They’ve since gone even further, creating what’s been described as “a synthetic cell that contains the smallest genome of any known.”

Whew. The creating-rare-materials stuff seems a little less extreme than that. What kind of rare materials are we talking about here?

The most famous example—the one you’ll hear about in almost any story about the potential of synthetic biology—comes from the work of University of California–Berkeley-based scientist Jay Keasling, whose team found a way to modify E. coli—

Wait, I thought E. coli was deadly …

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Some strands can be, but there are many varieties, most of them perfectly safe. In fact, you’ve almost certainly got loads of it living in your intestines now, unless there’s something terribly wrong with you.

I’m … happy to hear that?

Anyway, they were able to modify E. coli and—to return to your initial question—yeast so that they would produce artemisinin, a powerful anti-malarial drug. As Michael Specter explains in a 2009 New Yorker article about the promises of synthetic biology, it’s one of our most effective treatments against an illness that “infects as many as five hundred million of the world’s poorest people every year and kills up to a million, most of whom are children under the age of five.” But artemisinin is normally difficult to produce and prohibitively expensive for many of the populations most devastated by malaria. Some estimates anticipated that Keasling’s method would reduce the drug’s cost per dosage by about 90 percent. A Parisian pharmaceutical company called Sanofi brought the synthetically produced drug to market on a nonprofit basis in 2014. But as Nature reported in February 2016, it hasn’t become a malaria game-changer, because the cost of plant-derived dosages has since fallen below that of the synthetic variety.

That model might be more effective for other drugs, but some researchers imagine even more powerful medical applications. For example, you might be able to modify cells in a way that makes them detect blood sugar levels in a host and then secretes insulin when they’re higher than they should be. If it were possible—and it’s probably still a long way off if it is, though experiments along these lines have already yielded positive results in mice—that solution could essentially free type-1 diabetics of cumbersome testing and dosing equipment.

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But it’s not just medicines, right?

Not at all! A more immediately practical application of synthetic biology—and this is another project that Keasling and many others have been working on—is the production of biofuels, once again by modifying organisms such as yeast and E. coli. The idea here—this is work that’s been funded by the U.S. Department of Energy—is that microorganisms already secrete chemical compounds. As with drug production, if you manipulate their metabolic pathways—the chemical reactions that turn sugar or whatever else they consume into a chemical byproduct—you can make them excrete oils instead. While that’s absolutely possible, there are numerous hurdles to pulling it off at an industrial scale, not least of which is that the production process can damage the cells themselves. If we can overcome such problems, though, synthetic biology might provide us with a truly renewable source of energy.

Hey, back to those lab-made or lab-tweaked life forms. What happens if these creations make it into the wild?

Unsurprisingly, synthetic biology evokes many of the same fears that have long chased other genetically modified organisms. But realistically, a barely alive microorganism probably isn’t going to do much damage, even if it does somehow end up outside a lab.

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Proponents of synthetic biology will tell you that we’ve been playing with genetics since the dawn of agriculture—and that new technologies simply allow us to do so with greater precision, care, and understanding. The bigger issue may be that there aren’t clearly defined regulatory standards for synthetic biology. Drug and food safety regulations can still apply, but that’s mostly about how products created through these studies make their way to market—which is a long way off for most work in the area. Researchers have laid out possible regulatory models, but for now most norms are informal, if they exist at all.

That sounds very soothing, but isn’t it just a matter of time before something goes wrong?

You aren’t the only one worried. In 2013 Kickstarter backers gave almost $500,000 to a campaign promising to produce glowing plants through synthetic biology. That worried a lot of people, including the Guardian’s Martin Lukacs, who called on Kickstarter to deny promised funds to the campaign, warning, “600,000 freak bioengineered seeds will be let loose across thousands of random locations in the USA–unregulated and uncontrolled.”

Kickstarter did eventually ban genetically modified organisms, but not until after the Glowing Plants project received its promised contributions. Ultimately, the project was brought down by an altogether different issue: Synthetic biology is really hard. As MIT Technology Review reports, another scientist’s attempt to make a bioluminescent plant had taken years of effort, and the results were still barely noticeable. The Glowing Plants team is still trying to make it work, but theirs is more a cautionary tale about promising too much than a story about the unintended consequences of science gone wrong.

It’s easy to imagine nightmarish synbio-powered science fiction scenarios such as terrorists designing custom viruses designed to target specific populations. Alternately, seemingly benign lab-grown organisms might behave in unexpected ways when they interact with ecosystems, threatening the natural balance. And, at a more structural level, some fear that these technologies could suddenly disrupt industries such as farming, potentially driving billions deeper into poverty.

But that’s all very far away. In many ways, it’s the very definition of an emerging field. Its promises are enormous, but progress remains incremental. We’ll be exploring some of those radical possibilities—as well as some the barriers that stand in their way—throughout this month’s Futurography course.

This article is part of the synthetic biology installment of Futurography, a series in which Future Tense introduces readers to the technologies that will define tomorrow. Each month, we’ll choose a new technology and break it down. Future Tense is a collaboration among Arizona State University, New America, and Slate.