A Blog by Jonathan Low


Mar 10, 2017

The Reason Biologists May Become the Next Rock-Star Tech Designers

Convergence and cross-channel integration are not limited to traditional technological silos. They now encompass entirely new disciplines whose insights may propel the next great wave of innovation. JL

Liz Stinson reports in Wired:

Synthetic biology views DNA as something to be manipulated and rearranged. Biologists can build organisms capable of anything imaginable with a degree of reproducibility typically reserved for engineering. Biology is like an integrated computer circuit that can be programmed; only instead (of) ones and zeros, you’re tinkering with genes and proteins. Genetic architecture (designs) with aesthetic, utilitarian, and social considerations in mind.
“Here. Smell this.”
Effendi Leonard smiles and pushes a vial of pale, cloudy liquid toward me, like a grandfather offering a plate of cookies. I unscrew the cap and take a whiff. The scent is earthy, a bit like rising dough. “It smells like bread,” I tell him.
He beams but doesn’t say anything, then hands me another vial. “And this?”
This one smells sweet, like fruit, but harder to place. I inhale again and guess. “Grape soda?”
We’re standing around a lab table at Ginkgo BioWorks, a Boston biotech company, playing Name That Smell. I was right. The second vial is meant to smell like grapes, though you’d never know that from its contents. There isn’t the slightest trace of grape in it. In fact, designers created it using “a regular baker’s yeast,” says Leonard, an organism designer at Ginkgo.
To make something that smells like grapes without using grapes, designers inserted genes from various plants, including corn, into the basic yeast “chassis” to build a new genetic architecture. The redesigned genetic sequence gave rise to a variant of yeast that, when fermented, produces a chemical that smells distinctly of grapes. The sweetness, the tartness, the hint of dirt—it’s all there, emanating from a tube full of fungus. You could describe Ginkgo BioWorks as a biotech startup, a research lab, or a well-funded band of biohackers. Ginkgo calls itself an organism design foundry. Semantics, perhaps, but the wording is important. Throughout history, biologists have focused on describing and understanding the natural world. But a greater understanding of life’s building blocks has given them a greater proclivity for engineering and designing organisms.
This creative practice, which falls under the umbrella term synthetic biology, views DNA as something to be manipulated and rearranged. Proponents see a day when biologists can build organisms capable of anything imaginable with a degree of reproducibility typically reserved for engineering. In this new world where biotech companies like Ginkgo and Amyris and Craig Venter’s Synthetic Genomics play, biologists become designers working with one of the most powerful substrates imaginable: life.
In this new world, biologists become designers working with one of the most powerful substrates imaginable: life.
Advocates of this technology promise revolutionary advancements in everything from green energy to medicine to food production. That has brought money pouring in. The so-called bioeconomy already generates $350 billion annually in the US, according to one report, with much of it coming from the creation of biochemicals, biological feedstock, and biofuels. Still grander ideas—eradicating Lyme disease or malaria, terraforming Mars, or resurrecting extinct species—underscore why the opportunities presented by this technology exhilarate, and terrify, people.
“There are quite a lot of philosophical and ethical questions we need to explore rather than jumping right into designing biological systems,” says Oron Catts, an artist who leads the University of Western Australia’s SymbioticA program, which explores the intersection of art, design, and synthetic biology.
Beyond the science lies the ethics and oversight. How can science and society ensure such technology is used for the greater good? How should it be regulated, and by whom? And what of the unintended consequences that inevitably will arise when people begin meddling with the foundation of life? “It’s a very complex issue,” Catts says. “We need to be having a nuanced conversation.”
That conversation, traditionally led by scientists, is drawing people from beyond the lab. Designers and artists are shaping the future of synthetic biology by helping scientists understand the power of this technology. Their participation is vital, says Kevin Esvelt, an evolutionary biologist at Harvard’s Wyss Institute, who’s exploring how synthetic biology might help eradicate diseases like malaria by inserting disease-resistant gene drives into some species of mosquitoes. Scientists, unlike designers or artists, are often hyper-focused in their research. “Scientists are not scientists because they want to change the world,” he says. “They’re scientists because they’re interested in increasing human knowledge, which may have direct benefits on changing the world for the better.” Esvelt believes synthetic biologists, perhaps more so than other scientists, are in a position to think differently about their field. They can—and have already begun— to adopt a more holistic way of viewing their work, in no small part due to their collaborations with artists and designers who possess tools and ways of thinking that they themselves do not. “It forces us to be philosophical in ways that other areas don’t have to be,” he says. “And I think we should embrace it.”

Foundry Of Life

MIT professor Tom Knight co-founded Ginkgo BioWorks seven years ago with a handful of his biological engineering doctoral students. It operates out of an old factory overlooking Boston Harbor in the city’s Seaport neighborhood. “I like to say that we’re the only startup with a better view than its lawyers,” Knight says.
Knight is perhaps best known for his seminal work in electrical engineering in the 1980s, though he—along with pioneers like Harvard geneticist George Church and biotechnologist-cum-entrepreneur Craig Venter—is regarded as one of the grandfathers of synthetic biology. It’s an apt description—between his puffy white beard and warm-but-wonky demeanor, Knight comes across as something of a hybrid between Einstein and Santa Claus.Ginkgo’s headquarters is full of scientific ephemera: Turtles swim in a tub in the kitchen, a Ginkgo-emblazoned hazmat suit hangs on the wall, company T-shirts feature a Jurassic Park logo and the tagline “There Will Be Dragons.” Towering shelves line the entryway, packed with books with titles like Culturing Life, Genetics: Second Edition, and Methods in Enzymology. 
The team has 18,000 square feet of space, and a second round of funding—$45-million—from Viking Global, Y Combinator, and OS Fund has it looking to significantly expand BioWorks 1, the biological foundry that opened earlier this year into a second foundry called BioWorks 2.
The first thing you notice in the bright white lab are the robots. They’re everywhere. Ginkgo has one for nearly every step in the organism-synthesizing process—there’s a robot devoted to pipetting drops of DNA, a robot in charge of fermenting yeast, and another robot for analyzing the molecular composition of the yeasts’ fermentation products. But Ginkgo’s labor force isn’t totally robotic; biologists are also on hand to shuttle samples from one machine to the next. “One of the dreams while we were building out the foundry was that maybe it would be totally automated; you’d have robotic arms moving samples around,” says Patrick Boyle, another organism designer at Ginkgo. “It turns out that the way we put workflows together and do experiments in a lab, people are just more efficient at some of these processes.”
Remixing life is intensely physical. It requires mixing bits of DNA, often in the form of tiny drops of solution Ginkgo buys from sequencing companies. Stitching together a new genome is something you do by hand, if you don’t have a robot to do it for you—and cutting and pasting DNA is painstaking work. “You’d spend two-thirds of your time putting DNA together, which isn’t an interesting thing for a designer,” says Ginkgo’s creative director, Christina Agapakis, of her time working in research labs. “You want to see what it does when you’re done with it.”
Separating the design and creation processes has freed Ginkgo’s crew to spend more time thinking about the design of the organisms it’s creating. Think of it as the difference between architects and contractors, says Drew Endy, a professor of biological engineering at Stanford and former MIT professor who worked with Knight. The architect comes up with a vision, and the contractors execute on that vision. He puts it another way: “Jony Ive, how good is he at building a silicon wafer? Approximately, not at all.”
By automating tedious lab tasks, Ginkgo can generate strains at an otherwise unthinkable rate. “Our design approach is to simply build as many prototypes as we can,” Boyle says. “You can fit literally billions of different prototypes on a petri dish. You don’t want to look at them all, but you can generate that many.” Ginkgo’s samples, which include live organisms and pieces of purified DNA, are held in tiny tubes labeled with a barcode; scanning these tubes reveals the creation date and genealogy of the sample. Lab co-founder Jason Kelly says the team sequences hundred of enzymes from a database that catalogs nature’s diversity to glean a better understanding of their behavior. “We don’t just quickly screen these enzymes for the specific activity we’re looking for but rather test them more deeply to catch activities we might not predict,” he says. Ginkgo tracks all of this information in an enormous database, which is what helps the company’s software generate what the designers hope will be increasingly accurate predictions of which biological parts work together to produce certain compounds. “That’s really why you need that foundry scale,” Boyle says. “Because we don’t know all the design rules yet.”
Once those rules are more fully understood, the Ginkgo team will be able to design organisms more efficiently. “I think understanding has to come before the manipulation,” Knight says. In that way, designing organisms mirrors designing with more traditional substrates like wood or code: A deeper understanding of the material leads to better designs.
Ginkgo collects this info in a Github-style Wiki. Software developers—who comprise one-third of the company’s staff—translate that data into design principles that help the robots mix and match certain genes more efficiently. This allows the designers, as Boyle describes it, to “shoot in the dark effectively,” freeing up time for them to conceptualize and solve problems.
Nature relies on the glacial pace of evolution to dictate a biological solution, but Ginkgo’s designers must work faster—they have customers to answer to. In many ways, the company is like any industrial design firm. It has contracts for more than 20 organisms from customers that include Ajinomoto, a Japanese food and chemical company seeking a yeast strain for animal feed; a major beverage company that wants a new sweetener; and another looking for an organic pesticide.
When I visited the lab, designers were working through a brief from Robertet. The French perfume company wanted Ginkgo to engineer a strain of yeast capable of producing rose oil. The yeast-derived rose oil would be more sustainable and less expensive to produce than oil from actual roses, the availability of which can be inconsistent, thanks to the unpredictabilities of things like climate and disease. It’s not a new idea: In the late ’80s, scientists genetically modified E. coli to synthesize chymosin, the enzyme used to turn milk into cheese. Most cheeses are now made with GMO-derived chymosin, which is cheaper and more reliable to produce with microbes than it is to harvest from the stomachs of baby cows.
Rose oil derived from genetically engineered yeast has all the complexity and nuance of the real thing. “When you smell a rose, you’re not smelling a single compound that is the rose smell,” says Boyle, “you’re smelling all the different compounds that rose makes.” Thousands of different molecules, he says, contribute to the fragrance profile of a rose’s essential oils. By comparison, a rose accord—a combination of compounds that approximate’s a rose’s scent—typically contains just three or four chemical compounds. “Rose essential oil is like an orchestra or symphony whereas rose accord would be more like a string quartet,” he says. “You can play the same notes, but you don’t get the same overall impression.”

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But the chemicals Ginkgo is making don’t come from a rose, exactly. By selecting specific genes from roses and crossing them with yeast DNA, “we’re taking the exact biochemical pathways from a rose and putting them into yeast,” Boyle says. The result is a genetically modified strain of fungus that produces a cocktail of chemicals close to the one produced by an actual rose. By separating those chemicals from the yeast that produced them, Boyle’s team is left with a product that smells remarkably like natural rose oil’s symphony of fragrance.
Ginkgo started in late 2008 with $15 million in funding from Darpa. Its aim was to design synthetic probiotics that could reduce gastrointestinal problems in soldiers. That project is still ongoing, but, according to Kelly, is in “very early stage research.” For now, the startup is focusing on fragrances and flavors like natural sweeteners (they just signed a new multi-million-dollar contract with Robertet to synthesize lactones, which impart a sweet, creamy scent to fragrances). Knight concedes that’s not the most headline-worthy of ambitions, especially when you consider what’s possible with Crispr, a technology that allows scientists to edit genomes by cutting and pasting bits of DNA. “My goal is to get into much more complex organisms, but I have no illusions about that happening anytime soon,” he says. “There’s a reason why we’re working with simple organisms; we’re having a hard enough time understanding what they do.”
There are practical considerations at play, too. Fragrance and flavors can be brought to market more quickly than, say, pharmaceuticals or biofuels, both of which are more heavily regulated, have a lower return on investment, and can take decades to develop. “There’s very little that is going to stand in the way of making short term profits out of this,” Knight says. “That money, certainly if I had my way, will be re-invested in the development of the technology and will make us able to engineer biology more effectively. That’s what it’s about.”

Biology Goes Industrial

One afternoon, Knight is sitting in his office at Ginkgo BioWorks pondering how he might put the foundry’s additional space to use, once it’s finished expanding after its most recent round of funding. One thing he’d like to do is build a cabinet of curiosities and fill it with scientific novelties—animals, fossils, and other strange or interesting things he comes across. “Here’s one of my favorite objects,” he says, lifting a reflective sphere about the size of a grapefruit from his desk. “This is my crystal ball. Most people have crystal balls that aren’t really crystals, but this one really is a crystal ball. Do you know what it is?” he asks, turning it over in his hand. “It’s silicon—pure silicon. This lets me see the future.”
Biology, it’s said, is like an integrated computer circuit that can be programmed.
Before starting Ginkgo, Knight was a researcher and professor at MIT, where he taught electrical engineering. Knight sees many parallels between what he does today and what he did in the 1980s when he was miniaturizing transistors. It’s common in the synthetic biology world for researchers to compare their work to the early days of computer programming. It’s a metaphor that makes the dizzying world of biology a little easier to grasp. Biology, it’s said, is like an integrated computer circuit that can be programmed; only instead manipulating ones and zeros, you’re tinkering with genes, RNA, and proteins.  The silicon ball, then, is an apt metaphor for what Knight and his colleagues hope to achieve at the foundry: The purity of the ball is a feat of man, not of nature. “This silicon ball is ridiculously pure. It could never occur in nature,” he says. “Somebody had to go to a lot of trouble to make it as pure as it is now.” Biology, like this silicon ball once was, is incredibly messy and complex. Knight believes that to make progress, biology has to be as simple as this shiny sphere, and that requires human intervention. “A lot of what we’ve been doing over the last several years is intentionally making biology simpler,” he says.
In 2001, Knight introduced this idea in the form of BioBricks, a standardization system designed to help biologists assemble complex sequences of genetic code. A DNA segment that adhered to the BioBrick Standard was called a “part.” Each part coded for a specific biological function, and was catalogued in a registry. The idea was that biologists could pick and choose parts from the registry like bricks from a bin of Lego, and snap them together into increasingly complex combinations of genetic instructions (aka “devices”) that could later operate inside a living cell. Back when the BioBrick repository housed just six parts, the idea seemed pretty ridiculous. But today, the repository contains more than 20,000 parts. It’s also the official registry of iGEM, an international competition that challenges students to build novel biological systems out of BioBricks parts. Needless to say, the idea no longer seems so far fetched.
Ginkgo doesn’t adhere to the BioBricks Standard (it’s too simplistic for Ginkgo’s purposes, and the company is looking to outsource more of its DNA synthesis), but Knight says they were an important precursor to Ginkgo, because it changed how people thought about living systems. “It’s the enabler to the kind of technology you’re seeing here,” he explains. “It’s the enabler of transitioning away from the artisanal craft of biology to the industrial scale.”

Thinking Like A Designer

If biology no longer requires a hand-crafted approach, it frees up scientists to consider the applications—and implications—of the technology. In his class, Foundations for Engineering Biology, Endy no longer teaches undergraduate students how to cut and paste DNA because he’d rather them think about what they want to design with DNA. “Design in the scope of biology has a lot to do with judgment. It’s not necessarily about knowing what to do, but knowing when to do it,” he says. It turns out that once biological engineers are equipped with technical skills, there’s an even bigger, and arguably more important, question to answer: What will they do with these tools?
Esvelt, of Harvard, thinks about that question often. Tools like Crispr are wildly powerful, but with power comes responsibility. “We have never before had the power to pretty much unilaterally alter the shared environment,” he says. Synthetic biology opens the door to more “specific and elegant” solutions to many man-made problems, Esvelt says, but he’s not blind to the fact that this raises urgent questions about how such manipulations might affect other organisms in an ecosystem. “Even if you’re reasonably sure that there aren’t going to be side effects, how on earth can we decide whether or not we should use it and when we should use it?” he asks.
That’s where thinking like a designer comes into play. Despite having trained as scientists, many synthetic biologists are slowly acknowledging that design thinking, in addition to technical understanding, is an essential skill. The evolutionary process is iterative, but it is mindless. The person who designs genetic architecture, on the other hand, does so with aesthetic, utilitarian, and social considerations in mind. 
“I believe scientists are not designers, and designers are not scientists,” says Paola Antonelli, senior curator of design and architecture at the Museum of Modern Art, who has said that biodesign will be one of the most important design fields in the future. What she means is that both disciplines bring a distinct set of skills that contribute to the advancement of synthetic biology, and are most effective when they work together. Designers are drawn to the field of synthetic biology for the same reason scientists have begun to adopt design thinking—using biological matter as a material can lead to some wildly creative possibilities. Last month in New York City, designer Suzanne Lee organized a day-long symposium called Biofabricate that brought together a few dozen designers, scientists, and artists who have been working with the medium of life. Lee is the founder of Biocouture, a startup that’s investigating how synthetic biology will impact consumer goods, and the conference was a like a demo day for researchers and designers working in the field. There were aesthetic works on display like scarves dyed with ink made from bacteria and a prototype for a self-folding shoe that reacts to humidity. But alongside visual designers there were molecular biologists, Harvard scientists, architects, and bioethicists. The field is beginning to blur the boundaries of disciplines, which is important says Agapakis, Ginkgo’s creative director. “People are approaching the field and asking these really complicated questions like, what does it mean to design a living thing?” she says. “What does it mean to design a beautiful life form?”
Using biological matter as a material can lead to some wildly creative possibilities.
In Synthetic Aesthetics, Endy, designer Alexandra Daisy Ginsberg, and a handful of other designers and engineers explore Agapakis’ question. In the book, social scientist Pablo Schyfter explains that at its core, design is about making a series of weighted choices. “Design doesn’t happen for its own sake: It is always motivated by something.” In that way, synthetic biology, with its commercial aspirations, ultimately comes down to a series of judgment calls. “The best biologists I’ve ever worked with are the best people at choosing what to work on and choosing when to kill projects,” Endy says. “And I think that has a lot to do with the design process.”
Ginsberg, a designer who Antonelli describes as the “goddess of synthetic biology,” believes it’s the role of designers to ask uncomfortable questions of the technologists and scientists who are working in these fields. “I think it’s a social issue, not just a technological issue,” she says. “I think imagining technology can solve our problems is kind of a techno-utopian view and I think it’s much more complex. It’s about how we behave and build our societies, which technology can be a part of.”
Synthetic biology would have a real-world impact on politics, employment, and land-use. Endy points to the creation of synthetic Artemisinin, a malaria vaccine derived from wormwood plants. If you were to start producing Artemisinin in yeast instead of through wormwood, which is now possible, what does that mean? “On one hand, it sounds really good,” he says. The synthetic variety reduces land use by an exponential amount, which in theory opens it up for food production. “On the other hand, it looks like you’re replacing the jobs of 100,000 people who grow trees with about a couple hundred people who grow potatoes. Who is talking about that?”
Designers have in some ways become the ethical whistleblowers of the field, using the process of speculative design to ponder what a synthetic future will look like (see Ginsberg’s Designing For the Sixth Extinction). Rodrigo Martinez, a researcher at Ideo Boston who focuses on life sciences and synthetic biology, believes that there’s a lot of room for synthetic biologists and designers to work together, and that this union will push the field not just forward but in the right direction. He and his team look at the future of synthetic biology by crafting stories around possible futures. This helps both scientists and the public crystallize how this technology could possibly be used in the coming decades. “There’s an opportunity for designers to not just help with the packaging of science or technology, but telling stories about what it is that it does and how it does it,” he says. “Especially in an area like synthetic biology where it’s not easy.”
Martinez says we often tell stories about the world we want before it actually comes to into existence. By imagining possible futures, we’re effectively deciding what kind of future we want to create. And the fact is, we’ve barely started exploring what’s possible with this technology. Martinez and his team are working on ways to extrapolate synthetic biology’s impact into the future, to a time when it will have an impact on our children or grandchildren. It probably won’t look like Jurassic Park or genetically designed offspring—at least not anytime soon—but rather as biology embedded into more nuanced moments of our daily lives. Things like bio-sensors that monitor air quality or at-home kits that allow kids to tweak living matter. Maybe, Endy says half-jokingly but with true optimism, we’ll even be able to program a bush in our garden to grow into the shape of a unicorn. “I can’t imagine,” he says, “not being able to pull that off eventually.”


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