The Meaning of (Making) Life

A synthetic biologist explores the intersection of culture, art, and microbes -- and cheese too.
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Christina Agapakis is a rising star among the new generation of biology researchers. Trained in the science of custom-building organisms known as synthetic biology, the UCLA researcher likes to think about the way her field intersects with culture and industry more broadly.

Case in point: Through a program of the BioBricks Foundation, she worked with artist Sissel Tolaas to create cheeses cultured with the microbes that help produce our body odor. The project highlights the meaning that humans assign to the productions of the invisible world of bacteria. And Agapakis wants us to rethink our relationships with the microbial communities that live in and around us.

"Re-contextualizing these ostensibly 'bad' smells, we saw that when the odor is in cheese it smells good and it's a sign of culture and good taste. But the same smell on a body is disgusting," she told me an interview for our most recent issue. "By making cheese using bacteria from the body, we're showing that we should be able to think about the microbes in our lives in different ways."

Since the beginning of the 20th century, we've learned so much about the machinery that powers life, but the larger societal and political issues that the biosciences raise receive far less attention than technological developments like smartphones or social networks. Biology is so complex that we need people like Agapakis who provide pathways towards a better understanding of how we interact with all the life we can't see.

In this extended remix of the print Q&A, we talk about the long-term potential of biology, that cheese project, and the potential to engineer the microbial ecosystems of our digestive tracts.

People have big expectations for biology in the 21st century. Many say that biotech will be as big as information technology was in recent decades. Is that true?

People want synthetic biology and biotechnology to be the next industrial revolution. Looking back, people have tended over time to imagine bodies functioning in ways that were analogous to the dominant technological paradigm of their day, whether that was steam engines or computers. I hope that soon biology will be the technology we judge things by. Maybe we're going to see industry and computational stuff start to look more like biology, rather than biology looking more like industry and computation.

What would it mean to have industry look like biology?

Well, people are trying to push synthetic biology [in the direction of] the chemical industry--to replace any petrochemical with a biological process. You could have a vat of bacteria that's going to make the chemicals that you want. That model can be good, but it's limited. It isn't trying to rethink the way we use chemicals and do industry. Daisy Ginsberg, an artist and a writer and designer, says, "It's a disruptive technology that doesn't really disrupt anything." If we still have gasoline, just made of bacteria in a vat, that may not be the right vision for the future.

People talk about creating standard DNA "parts," called BioBricks. What are those?

The idea behind BioBrick parts is that you can have a collection of pieces of DNA that have specific useful functions---off-the-shelf DNA parts. You are able to say, "Okay, I need a part that is fluorescent," or "I need a part that will activate in response to this chemical." Then you can mix and match: you put them both in a bacterium, and then you have fluorescence in response to some chemical--so we can have this kind of RadioShack.

It seems like the human body is getting more attention as an ecosystem of microbes and human cells working together. You explored this in a fascinating way by making cheese with human skin bacteria, right?

I was getting really into microbial ecology when I started a design fellowship with an arts and science group, Synthetic Aesthetics. I was moving away from the BioBrick model and into mixing and matching of whole cells. I was paired with Sissel Tolaas, who is an odor researcher. She calls herself a professional provocateur-- she lives between a lot of different fields, from perfumery and odor science to in-your-face art projects. She'll do things like paint people's body odors on walls in galleries.

Gross!

It's not connected to the armpit, it's not as gross, but it is kind of gross. So why is it gross? She says things like, "Nothing stinks, only thinking makes it so." I was really interested in saying, "OK, where does body odor come from?" It's from this relationship between the bacteria that live on our skin and our own metabolism. We Googled "body odor," and we kept finding the molecule responsible for body odor was Isovaleric Acid--that's a really sweaty smell. Then we looked at some of the microbes responsible [for producing Isovaleric Acid] and we found propioni bacteria. When you just Google "Isovaleric Acid Propionibacterium," the whole first page of Google is about Swiss cheese.

This is still gross. But go on.

Re-contextualizing these ostensibly "bad" smells, we saw that when the odor is in cheese it smells good and it's a sign of culture and good taste. But the same smell on a body is disgusting. By making cheese using bacteria from the body, we're showing that we should be able to think about the microbes in our lives in different ways.

To what extent could we actively engineer our own microbial ecosystem in the future?

We can influence it--we can change the diversity in our gut, and that can influence health. There's the fecal-transplant example: Sometimes even antibiotics can't clear up serious digestive infections, and you can't repopulate the gut with enough good bacteria to get rid of the bad ones. But if you transplant the microbial community from a healthy gut into the person who has this infection, the healthy bacteria will push out the infectious bacteria. The challenge is, you can't say "You need this many of this and this many of this, and it's going to stay like that forever." It's more a matter of setting the right initial conditions.

There seems to be a tension between the complexity of life, which only gets more intricate the closer you look, and the speed of improvement in the DNA-sequencing technologies that allow us to see that intricacy. The more we learn about the building blocks of life, the more we realize just how much we still don't understand. Which will win out in the short term--the sense that we know more than ever, or the sense that life is even more mysterious than we'd grasped?

It's not really a matter of "winning." Tools that read and write DNA help us understand that complexity, but they're not enough. Sequencing is not going to tell you how genes are activated, how proteins interact with each other, how the cell inter-acts with its environment and with other cells. We're seeing, in the explosion of other kinds of "-omes" [for example, genomes, proteomes, metabolomes], a complexity that will require more than DNA sequencing to decipher.

The price of DNA synthesis is falling, but the overall price of synthetic-biology projects isn't going down at the same pace, because there is a lot more to the design, construction, and testing of synthetic systems. As Stanford's Drew Endy likes to say, "Just because we can write DNA doesn't mean we know what to say." An artful biological design is an incredibly complex endeavor, not just because of the complexity inside the cell. We also have to think about how applications will be marketed, regulated, and patented; how they will interact with the environment; and many other things that we won't learn from just the sequence--if at all.

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Alexis C. Madrigal

Alexis Madrigal is a senior editor at The Atlantic, where he oversees the Technology Channel. He's the author of Powering the Dream: The History and Promise of Green Technology. More

The New York Observer calls Madrigal "for all intents and purposes, the perfect modern reporter." He co-founded Longshot magazine, a high-speed media experiment that garnered attention from The New York Times, The Wall Street Journal, and the BBC. While at Wired.com, he built Wired Science into one of the most popular blogs in the world. The site was nominated for best magazine blog by the MPA and best science Web site in the 2009 Webby Awards. He also co-founded Haiti ReWired, a groundbreaking community dedicated to the discussion of technology, infrastructure, and the future of Haiti.

He's spoken at Stanford, CalTech, Berkeley, SXSW, E3, and the National Renewable Energy Laboratory, and his writing was anthologized in Best Technology Writing 2010 (Yale University Press).

Madrigal is a visiting scholar at the University of California at Berkeley's Office for the History of Science and Technology. Born in Mexico City, he grew up in the exurbs north of Portland, Oregon, and now lives in Oakland.

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