Synthetic biology is all the rage given its potential to upend science as we know it. But what it’s giving Luis Campos is a serious case of déjà vu.
By Sally Ann Flecker
“Have you looked at the news in the last few days?” Luis Campos asked in a lively voice at the start of a phone conversation recently. “Craig Venter has claimed to create a synthetic cell.”
Venter, of course, is the entrepreneurial biologist who led the private push to sequence the entire human genome, racing against the publicly funded Human Genome Project. Now his team at the Rockland, Md.–based J. Craig Venter Institute, using lab chemicals and a computer, has created the first viable cell with a synthetic genome.
It’s not surprising that Venter’s name surfaces in the conversation. What Campos, an assistant professor of history who specializes in the history of science, has been documenting lately is the edgy science that Venter and others are doing, and it’s unfolding right now, not in the distant past. It’s a new and—depending on your viewpoint—exciting or unnerving field called synthetic biology. The simplest way to describe synthetic biology is that it’s where engineering and biology converge, with genetics, chemistry and computer science thrown into the mix. What makes it sexy—and increasingly appealing to a generation of budding young scientists—is the promise of creating entirely original sequences of DNA that allow an organism to do something other than what it’s naturally able to do.
It’s that word “creation” that Campos finds compelling. As a historian of science, he looks at science not in a Petri dish but as a part of culture. One of the things he’s been following is the way the term “playing God” gets bandied about uneasily in relation to certain kinds of scientific advances. According to Campos, the accusation is nothing new. In his work he’s explored biology in the first half of the 20th century when geneticists were the new kids on the block, and there was a buzz, much like today, over using science to create new, bigger, better organisms.
With the emergence of synthetic biology, it’s just been a matter of time, he’s been saying, until the claim of creating life in a test tube comes along—and then someone else will deny it happened. That’s what’s got Campos so excited over Venter’s announcement—not the accomplishment as much as the response. Almost immediately, for instance, the Vatican seemed compelled to comment on the breakthrough, acknowledging it as “interesting,” but countering that the scientists who created the cell had not created life, just “replaced one of its motors.”
Meanwhile, President Barack Obama directed the newly minted Presidential Commission for the Study of Bioethical Issues to consider the potential medical, environmental and security benefits while identifying possible risks. Which, of course, is the $64 million question: What exactly is this science capable of? And the answer is, nobody completely knows.
Campos was just up the road at Harvard, working on his dissertation in 2004, when synthetic biology pioneers at MIT organized a now-famous conference to bring together researchers from around the world. Campos was struck by the way they were describing what they wanted to do, and what the future of biology could be. The way they talked about biology as something that could be engineered, controlled and predicted echoed how biologists a hundred years ago had talked about their research. It occurred to Campos that his perspective—the long view—might be relevant. “I thought, how unusual is that for a historian to be working on something that might actually be of direct interest to people who are doing the science today,” he says.
Campos submitted a proposal, offering to talk about the parallels he had uncovered. “We didn’t even know our field had a history,” organizers told him. “They thought this was a new way of thinking of biology,” he says. “Understandably, they didn’t know this larger history, something that has come and gone in various ways over the course of the century.”
Campos told them several stories about attempts in the early part of the 20th century to create life as a way to get at the basic nature of living things. (One notable experiment involved radium and beef bouillon, producing strands that appeared lifelike in some ways.) “Oh no, we’re not trying to create life,” they responded. “We’re trying to engineer life.” Campos finds it interesting that they feel a need to make that distinction. “For people at the beginning of the 20th century, the proof that you had a proper engineering understanding and approach to biology was the ability to create it yourself,” he says. “If you understood life properly and fully, then you could make it.”
Although Campos didn’t end up speaking at the conference, he did attend and was blown away, he says, by the way they were reconceptualizing biology. “I had never heard biology described in terms of computer-engineering terminology. Think of logic gates and gene circuits. Who are these people?” he says.
To hear scientists talk about the promise of synthetic biology, it’s going to usher in a new era of personalized pharmaceuticals, solve the petrochemical fuel crisis, clean up the environment. And some of it is more than promise. There are synthetic biologically engineered systems already in commercial development, such as new biofuels engineered from E. coli bacteria. Or take the same E. coli bacteria, this time engineered to make a cheaper artemisinin, the basis of an existing and effective antimalarial drug.
Biology, through the eyes of a synthetic biologist, is looked at as a technology. DNA is something that can be “programmed.” Living organisms are biological “machines.” Genetic codes can be rewritten. Scientists in the field talk about standardized parts (DNA sequences with identified functions), chassis (the structural framework, often bacteria or yeast) and devices (combinations of basic DNA parts). They call genetic engineers, who use genes to tweak existing organisms and systems, “gene bashers.” They imagine a virtual toolbox full of interchangeable BioBricks, pieces of DNA that connect together like Legos, to create organisms that function in a wholly new way. (The trophy for MIT’s wildly popular International Genetically Engineered Machine competition for undergrad students of synthetic biology is a shiny silver, brick-sized Lego.)
The field is changing and expanding so quickly that in the last five years at least four different approaches have sprung up, according to Campos. “One is parts-based—designing Legolike BioBricks. That’s MIT,” says Campos. Another method uses metabolic engineering to produce disease-curing chemicals that are provided only by endangered species. “That’s what Berkeley’s been doing with artemisinin, a cure for malaria,” Campos points out. “Then there’s the minimal genome approach, which is what Venter has been doing—how small can you make a genome to prevent the interference of having too many genes [complicating the results]. You just simplify the system.” Finally, there is a pure science, primarily European, approach that uses synthetic biology to shed light on how life may have originated on the planet.
This is a heady time for synthetic biologists. Its foundations as a discipline are still being developed. Campos describes the field as being in its adolescence. But for the time being, it feels like the heyday of the U.S. space program—limited only by the imagination of the practitioners.
As an undergraduate biology major at Harvard, Campos took a biology seminar that involved building a meta-phylogeny to understand the nuances of how certain families of plants and ants evolved together. The course provided an epiphany for Campos. He noticed that in the separate studies being created for this super-sized family tree, there were differences in the ways individual species had been defined. It piqued his curiosity. “For me, asking the question about the proper method was just as interesting as trying to figure out what actually happened in evolutionary history. I had discovered, in the course of doing my biology degree, I was more interested in questions about the nature of knowledge or why it is that we believe this rather than that,” he says. In other words, he was ready to study the history of science—which he did, first at Cambridge, where he got his master’s in the history and philosophy of science, and then back at Harvard for his Ph.D. work.
He brought this same questioning attitude to his dissertation on the prehistory of radiation genetics. It’s hard to imagine now, but when radium was first discovered at the turn of the last century, the popular belief that it had life-giving properties actually affected the interpretation of scientific experiments. Take one 1906 study where a plant, exposed to radium several times a week, grew strangely off to one side and then died. “We would say that’s damage,” Campos says. “But they understood that to be too much of a good thing, that the so-called life-giving power of radium had accelerated the plant’s life through its natural life span, and therefore, this was the expected result.”
As Campos studied how scientific and popular understandings of radium affected each other, he also began to notice the development of an engineering approach to biology, a morphing that began as early as the turn of the last century. He points to the influential botanist Hugo de Vries in the early 1900s, who advanced the idea of experimental evolution. Or physiologist Jacques Loeb, who discovered the phenomenon of artificial parthenogenesis in his famous experiment with sea urchin eggs, where a change in the concentration of salt in water stimulated eggs to develop without sperm. Or H.J. Muller’s work in the 1930s to produce mutations through X-ray irradiation. Synthetic biology didn’t originate a few years ago, Campos says, or in the 1990s, or even in the 1970s with recombinant DNA technology. In fact, he’s traced the first use of the term “synthetic biology” all the way back to Stéphane Leduc’s publication of La Biologie Synthétique in 1912. The engineering of biology, Campos says, was a central goal of the 20th century.
And, so far, of the 21st century as well.
Campos’ field work of late is much different from the long, quiet hours in a library looking at century-old correspondence. These days, he’s just as apt to be found at synthetic biology conferences, where he’s listening intently and furiously typing verbatim transcripts of the discussions into his laptop. (At top speed, he can do 110 words per minute.) “I’m listening in a very different way than how scientists and engineers are listening. They’re listening for what the new discovery is. And I’m listening for which kind of work is now, two years later, being referred to as a classic in the field—everyone just knows it,” he says. “How they’re arguing about certain things that were not even thought to be arguable a couple years before. Or what the interesting metaphors are that they’re using, but that they’re not aware they’re using, and how that affects the development of the field.”
Last year, biosafety scientist Markus Schmidt of the Austrian think tank International Dialogue and Conflict Management, which specializes in new bio- and energy technologies, invited Campos to write a chapter on contemporary synthetic biology for the book Synthetic Biology: The Technoscience and its Societal Consequences (Springer Netherlands). “Synbio is frequently alluded to as a ‘new’ idea/ approach/science and Luis showed in his work that the term synbio, as well as the idea behind it, is a recurring theme since the late 19th century. Luis identified several waves of synbio and described them with great insight,” Schmidt says. “Luis’ work on the history of synbio is the best I have seen in the community—a perception that is, I believe, shared by many synbio scientists.”
Google “synthetic biology” and you’ll inevitably run into someone accusing scientists of playing God—or scientists denying they are. Campos is tracking that societal tension as a “history of playing God.” He starts the story around the end of the 19th century with the new discipline of genetics taking off. Everyone was jumping on the bandwagon. Large agricultural stations were being created. Seed companies were competing fiercely by developing better cultivars. Horticulturist Luther Burbank, who developed hundreds of new varieties of fruits and flowers, was becoming famous through his plant catalogs, one of which was called “New Creations.” The production of novel things was an unquestioned good. “A scientist in the early days—even a nonscientist breeder like Luther Burbank—could say, ‘I’m going to make new creations,’ and everybody’s happy because they want better crops and better fruit,” Campos says.
But things begin to get more complicated by mid-century. Campos points to the atomic bomb, Rachel Carson’s Silent Spring, the Vietnam War, use of Agent Orange, the questioning of authority: “Science goes from being our salvation to being a more complex part of society.” There’s a loss of innocence in society, a burgeoning awareness of unintended consequences. “Playing God” becomes a recurring criticism by the time the new technology of recombinant DNA arrives in the 1970s. The debate is whether scientists are tinkering with or tampering with life. And that debate continues to this day.
Even the response Campos got from the conveners of the first synthetic biology conference, when they were careful to say they weren’t “creating” life, only engineering it, is telling. “The fear of being seen as the creators of new kinds of living things—and how that might lead to a backlash —is something that is a post-1970s response,” he says. “We have almost a complete inversion from the beginning of the 20th century until now,” says Campos, who eventually hopes to write a book on the history of “playing God” as a way to look at the larger history of genetic engineering, including the interaction between the public and the scientific community.
History, even of events taking place in the days of lightning-fast communication, requires the passage of time to temper the meaning. Still, says Campos, “It’s fascinating to watch how a discipline begins to emerge, and the time will come when we will want to know what happened in those early years and those early stages. And by sheer chance, I happened to be there.
“That’s sometimes how research happens, right?”
Sally Ann Flecker is a freelance writer in Pittsburgh and the former editor of Pitt Magazine.
The Idea of “Playing God”
This fall, Luis Campos and colleagues will present the thought-provoking symposium, “Playing God: Disciplinary Perspectives.” Joining Campos are Catherine Keller, professor of constructive theology from Drew’s Theological School, and Matthew Stanley, an associate professor and historian of science from New York University’s Gallatin School. The event is made possible with the support of the Rita and Melvin Wallerstein Faculty Development Grants, the Center on Religion, Culture & Conflict and the Campbell Colloquium on Science and Society.
Tuesday, Sept. 14, 7 p.m.
Founders Room, Mead Hall