BioHackers
By Azeen Ghorayshi
July 31, 2013 Reposted from the East Bay Express
A recent Kickstarter campaign to genetically engineer a glowing plant and distribute its seeds across the country has raised questions about the ethical responsibility of DIY scientists in the brave new world of synthetic biology.
What if we used trees to light our streets, instead of streetlamps?” That was the simple yet ambitious question posed by an April campaign on the crowd-funding website Kickstarter. The proposal? To produce a glowing plant by inserting genes from bioluminescent bacteria into the DNA of a small, wiry plant in the mustard family called Arabidopsis thalania. One day, the campaign hypothesized, such an accomplishment might lead to the engineering of glowing trees. “The potential is limited only by our greatest imagination,” the Kickstarter video declared.
The project promised to send backers who pledged more than $40 packets of fifty to one hundred genetically altered Arabidopsis seeds — allowing them to grow their very own glowing plants wherever they wished. The tagline — “Avatar’s Glowing Garden Becomes a Reality” — caught on instantly.
Within the first hour of going live, the Glowing Plant project hit 20 percent of its $65,000 goal. Within three days, funds soared well past that amount. By the time the Kickstarter effort ended on June 7, 8,433 backers had pledged roughly $484,000.
The idea of producing a glowing plant was not entirely new — one private company has been working on making them for the last year. But one thing that distinguished the Glowing Plant endeavor was the fact that the three men behind it — Omri Amirav-Drory, who owns a synthetic biology software firm in Berkeley; Antony Evans, a tech entrepreneur in San Francisco; and Kyle Taylor, a 29-year-old high school science teacher with a Ph.D from Stanford — were not attached to any private lab or university. Their research was being conducted in the so-called DIY bio world, a small but growing community of hackers, tinkerers, and off-hours science enthusiasts. And now they were going to make the fruits of their labor available to anyone.
As DNA has gotten cheaper and faster to sequence and synthesize, there has been a surge in interest around synthetic biology, which, at base, involves the engineering of new life forms with novel functions. The cost of sequencing the entire human genome has fallen from more than $95 million in 2001 to roughly $5,800 this year; synthesizing a single base pair of DNA now costs about 25 cents. Possible applications of the new biology-technology hybrid abound, including synthesizing vaccines faster than ever, making new biofuels, and creating novel biosensors to test water quality. A report this month by a New-York-based life sciences consulting firm estimated that the market for synthetic biology will grow to $16.7 billion over the next five years.
A side effect of this nosedive in costs has been increased access: These days, anyone can buy used lab-grade microscopes on eBay for a couple hundred dollars, and some have even claimed to be able to convert a webcam into a poor-man’s version for less than $10. As faster technologies are built, used DNA sequencers can be purchased online for a few hundred to a few thousand dollars. In many ways, this has blown open the door for anyone to start tinkering with biology, if only to engineer something novel like a glowing plant.
Yet almost as soon as the project was heralded as synthetic biology’s exciting mainstream debut, it also raised the ire of those who felt the public dispersal of such a genetically engineered plant would be irresponsible — and impossible to undo. Thus far, the DIY bio community has been entirely self-regulating. Never before had any of its members decided to release a genetically engineered organism to the public. Yet in doing so, Amirav-Drory, Evans, and Taylor effectively cast a critical spotlight on the DIY bio community, as well as on the burgeoning field of synthetic biology. As it turns out — with the exception of a few restrictions — it’s entirely legal to genetically engineer a plant and then release it into the environment, without much testing or oversight. In the new and rapidly changing world of synthetic biology, it’s become apparent that federal regulations are decades behind scientific reality.
Now, proprietors of the South Bay DIY lab BioCurious, where the Glowing Plant project did its initial work, are trying to decide whether it violates their self-designated safety codes. Meanwhile, staffers on Capitol Hill are realizing that existing federal rules are woefully unequipped to regulate such endeavors.
As companies and individuals become increasingly able to create new forms of life that we haven’t yet even imagined, the questions become: To what end should synthetic biology work toward? Who should regulate the field, and what sorts of regulations should be in place? Should there be stricter rules governing the DIY bio community?
And if not, what happens next?
The era of garage biology is upon us,” wrote Robert Carlson, author of Biology Is Technology: The Promise, Peril, and New Business of Engineering Life, in a 2005 op-ed in Wired. It was early on in the phenomenon, but a radical shift was occurring: People could, for the first time, conduct real scientific research without being part of the bigger machinery of a university or industry. But, for a while, no one really knew if such a thing was allowed.
For tinkerer Raymond McCauley, the struggle was figuring out how to best manage his self-described “little mad science laboratory in a garage,” where he was working on developing a “nano-mechanical DNA sorter.” So in 2009, the Mountain View-based bioinformaticist started meeting up with others who had similar homemade setups in their closets and kitchens, where they would fiddle away on projects at night after their day jobs.
At first, these so-called garage scientists proceeded cautiously, screening calls and keeping meeting locations secret. “No one was really sure what was okay and what wasn’t,” McCauley recalled. “Was this allowed? Were there any regulations about this?” But as time went on, the scientists realized that collaborating in a centralized location would be a more efficient, not to mention more open, way of doing things. “At first we just wanted a place we could put all our gadgets,” McCauley said. “But, fairly quickly, the people became more important than the gadgets themselves.”
And so, in 2010, after raising $35,000 on Kickstarter and setting up a permanent space in Sunnyvale, BioCurious was born. It joined a growing community of bio hackers: In the same month, a similar DIY lab called Genspace opened in Brooklyn. A couple years earlier, an online network called DIYbio.org was set up to organize the diffuse network of amateur scientists cropping up around the country. Its email listserv — a hotbed of ideas and debate — now goes out to more than 3,200 individuals. And it’s a motley crew, albeit one united fiercely in geekery and an eagerness to get their hands dirty: industry scientists pursuing side-projects off-hours, hackers, makers, and even a smattering of people with no technical background whatsoever. The policy of keeping the doors open to anyone has been central to the growing role of the biohackerspace as a public biology classroom: Participants often refer to the movement as the “democratizing” of science.
No longer secretive, DIY bio was fast becoming an open, community-driven collaboration by the late 2000s. Projects included such innovative ideas as 3D-printing live cells in hopes of making tissues and organs, as well as simpler projects like sequencing the DNA in grocery-store produce to see if it’s been genetically modified or not. Some in the community even hinted at the potential for commercializing the innovation fermenting inside the spaces. “Everyone would love to find some genius tinkering away in a garage,” McCauley said. And in the Bay Area, venture capital and tech entrepreneurs were beginning to take notice.
Kyle Taylor was approaching the end of his Ph.D focusing on plant pathology at Stanford University when he first came across BioCurious. Boyish and self-effacing, with wire-rim glasses and short blonde hair, Taylor grew up in rural Kansas — where, he said, “evolution just didn’t get taught.” Put off by the prospects of a post-doc and the tight bottleneck to academia — defined by its reliance on the ever-shrinking pool of grant money — Taylor decided to try an alternative route, teaching high school chemistry and biology by day, and tinkering around at BioCurious by night. “It seemed to me that if this whole DIY bio thing was going to succeed, it was going to be in the Bay Area,” Taylor surmised. “There’s just a lot of interesting people doing a lot of interesting and crazy things over here.”
Taylor began running his own experiments at BioCurious, teaching molecular biology classes in the space, and working on a community project playing around with bioluminescence genes in bacteria — attempting to insert the coded pathways that produce glowing into organisms like E. coli, algae, and, eventually, the Arabidopsis plant — when he was approached by Omri Amirav-Drory and Antony Evans. They, too, wanted to make a glowing plant, but they also had reason to believe there would be a market for the project on Kickstarter. “When we say ‘glowing plant,’ everyone gets that instantly, and people want it,” Evans said in a phone interview. “And I think a successful Kickstarter also needs to have some intangible, higher calling — a higher purpose behind it — which in our case is this long-term mission to use plants as street lights.”
Other scientists had already engineered glowing plants: In 1986, a group from UC San Diego showed that they could make tobacco plants express the firefly enzyme luciferase, so when the plant was sprayed with the chemical luciferin, it would temporarily emit a bluish-green glow. In 2010, a group in New York engineered a modified tobacco plant containing bacterial bioluminescence genes so that it produced a dim, but continuous, light all on its own.
Taylor believed he could use that latter method to create Amirav-Drory and Evans’ glowing plant, and signed on to the project. Some scientists have cast aspersions on whether the team will be able to get the plants to emit much light, but that hasn’t deterred it: “The path to streetlights may look something like Arabidopsis, a rose, and then maybe a bigger houseplant that is just a nice sort of ambient lighting for your house,” Evans said. “Then maybe we’ll work on the trees.”
That dream, however, remains in the realm of science fiction. The project — which has moved to its own lab space — is still in the initial cloning stages, but Taylor hopes to have Arabidopsis seeds ready to mail by May of next year.
Although the Glowing Plant team’s techniques are not new, its aims certainly are. University researchers and industry groups, for example, have long used a jellyfish gene for green fluorescent protein as a research tool, but that only glows when exposed to UV light. The Glowing Plant project’s altered Arabidopsis plant, if it’s successfully engineered, will emit light constantly. Once Taylor agreed to come onboard the Glowing Plant project as the team’s scientist, a debate quickly emerged over what it meant to make the glowing plants in the first place.
The issue came down to responsibility: Who can say, once the seeds are distributed, what people might do with them? What’s the worst that could happen? Has there been any precedent? And should the team be responsible to consider these issues in the first place?
“We debated that a lot, like, for months, internally,” said Evans, who, along with Amirav-Drory, was a strong proponent of distributing the seeds. “And at the end of the day, we came down on the fact that it’s legal, and the big goal of this is to educate and inspire people. Putting the seeds in people’s hands is the best way to do that. It’s clear that the seeds are what people wanted. And, you know, I think that validates it.”
Whereas in the grant-funded model scientists are, presumably, beholden to advancing the public good, the Glowing Plant team is beholden to the wishes of its backers, who are expecting to have their own glowing plants by early next year. But, many in the DIY bio world have argued, the team also has a responsibility to the community it has come to represent.
BioCurious’ safety policy forbids the release of any engineered organisms from the lab to the public. “Our lab is really a one-way lab; things go in, but they don’t go out,” said Kristina Hathaway, operations manager and board member of BioCurious. “They’re saying that there’s this loophole in which they aren’t violating guidelines. But do I think that’s the right thing to do? I don’t know that I do.” BioCurious is currently planning a community meeting to discuss the project and whether it will let the team move its research materials to its new space.
The issue boils down to stewardship. The DIY bio community is split between those who think that the project is a fantastic way to spotlight the cool new capabilities of synthetic biology, and those who think that a glowing plant — even if it’s legal and harmless to the environment — is bringing unwanted attention to a self-policing community that, until now, has had the privilege of doing its tinkering relatively free of federal regulation, mostly by veering far from the realm of recklessness. These independent scientists have been able to experiment freely because of the absence of any rules saying otherwise. In other words, the Glowing Plant project is only allowed to happen not because the rules say it can, but because there aren’t any rules that say it can’t.
One week after the launch of the Glowing Plant Kickstarter campaign, two environmental advocacy groups sent a letter to the US Department of Agriculture demanding that it put a stop to the project altogether. “This is bad policy and would set a dangerous precedent for all future agriculture biotechnology products and may pose risks to local environments,” they wrote.
It turns out that the distribution of a genetically engineered plant not intended for human consumption — with the exception of a few weeds known to have detrimental agricultural impacts — is entirely legal. In fact, the Glowing Plant project is not even required by law to test the plant’s ability to spread or its potential effects on the environment.
The reason goes back to a multibillion-dollar corporation known for keeping America’s lawns green — The Scotts Miracle-Gro Company — as well as the company that’s become the veritable poster child for genetically engineered crops — Monsanto. In 2011, Scotts Miracle-Gro designed a type of Kentucky bluegrass that was resistant to Monsanto’s common weed-killer, glyphosate, also known as Roundup.
According to a Reagan-era regulatory framework, oversight of genetic engineering is a fairly loose patchwork spread across a handful of federal agencies. Unlike so-called “Roundup-ready” corn, soy, and other crops, which fall under their own set of murky rules, the Scotts Miracle-Gro Kentucky bluegrass was exempt from regulation by the FDA because it was not a food product; similarly, the EPA had no say, because its jurisdiction is only over microorganisms.
Instead, the authority fell on the US Department of Agriculture, which oversees the release of genetically engineered plants. Scotts Miracle-Gro realized it only had to ensure two things in order to avoid any regulation of its genetically engineered bluegrass: The plant could not be a plant pest or involve the use of any plant pests, and the method of inserting the DNA could not involve the use of a certain type of bacteria commonly used to shuttle DNA into plants. The Kentucky bluegrass did not involve the use of any plant pests, and researchers used a gene gun to literally shoot microscopic pellets of the Roundup-resistant genes into the plant’s cells. Ultimately, Scotts Miracle-Gro was able to fully circumvent federal oversight.
Following this precedent, the Glowing Plant team is making use of the same loopholes. Thus, the USDA, much to the chagrin of environmental advocacy groups, has no authority over the project, or any other projects like it.
“I think a lot of these questions about the ecological impacts of introducing these sort of products is going to be — needs to be — reevaluated,” said Todd Kuiken, senior program associate at the Science and Technology Innovation Program at the Woodrow Wilson Center think tank in DC. “You can imagine in twenty years that if synthetic biology is really successful and takes off, then you’re going to have in a sense really novel plants that could potentially be introduced that you may need to evaluate, but that, under the current system, might not get triggered in any way based on how the laws are written.”
Kuiken first became interested in DIY bio a few years ago, when news reports in The New York Times and elsewhere warned that an unregulated underground network of garage scientists could — intentionally or unintentionally — synthesize new viruses, drugs, and bio-weapons that could potentially cause serious harm. “Amateurs Are New Fear in Creating Mutant Virus,” was one particularly alarming headline in the Times. Kuiken described the press coverage as a “magnifying glass” on the community, “stoking the flames of people’s fears in a way that was usually uncalled for.”
Part of this sensationalism was natural: DIY bio was a new endeavor, as was the field of synthetic biology. A small group of people possessing the tools to manipulate the most basic keys of life was, and continues to be, a somewhat unsettling fact for many. Yet, compared to private companies seeking to turn a profit, scientists in the DIY bio world sought to openly disclose the nature of their work.
Kuiken, whose work focuses on emerging technologies, saw DIY bio as posing interesting questions: “What happens when you get a community that is, in essence, made up of individuals that people have argued are coming from a sort of hacker ethos, and may not want to come together around sorts of codes of conduct?” he said. “We saw it is an opportunity to sort of help the movement ask these questions about risk … helping to sort of develop the community and make it a bit more coherent.”
The leaders of the DIY bio community were keen to do so, in a genuine attempt at letting the public know what they were doing and that they were taking the necessary safety precautions. In 2011, Kuiken and the founders of DIYbio.org helped organize two workshops, in London and San Francisco, each with about two dozen participants, who hammered out a sort of Hippocratic code of ethics for the community.
And yet, as described in a New York Times article last year, “the ethos is closer to scout manual than peer-reviewed journal.” The codes of ethics aim to foster good behavior, but there will always be aberrations — and what then? “One of the things to keep in mind is that with a trusting and open and transparent environment like this, you share what you’re doing with other people, and you share what you’re learning,” said Kavita Berger, associate director for the Center for Science, Technology, and Security Policy at the American Association for the Advancement of Science. “People share, give each other advice, post to forums — so there’s this sort of self-correcting type of mechanism already in place in the community. If one community member ends up doing something harmful, that affects everyone. So there’s an incentive for them to make sure that everyone is fully aware of the risks and the legal framework in which they’re doing their work.”
To keep an eye out for potential bioterrorism, about four years ago the DIY bio community formed a partnership with the FBI similar to the Department of Homeland Security’s anti-terrorism campaign “If You See Something, Say Something.” The DIY labs have coordinated communications with local FBI agents to report any suspicious activity within their spaces.
But on the biosafety side, DIY scientists have been pretty much left to their own discretion. Luckily, they’ve taken their self-regulating roles very seriously. “I’ve argued that they’ve taken a lot of these issues more seriously, and addressed them more directly, than a lot of industry labs do,” said Kuiken. “They know that if something were to go wrong, that has a much broader impact on them than if something were to go wrong at a university lab, for example.”
Which is a big reason why BioCurious proprietors are keeping a stranglehold on the work the Glowing Plant team performed at their lab. If McCauley, Hathaway, and the rest of the BioCurious board ultimately decide that the project’s decision to release seeds is something they deem reckless — however legal — they’ll strike down the material transfer agreement to allow the Glowing Plant team take its research to its new lab.
“Best practice in the industry is that you’re not just guided by what’s legal; you’re guided by civic duty and responsibility, and even the perception of the problem,” said McCauley. “Listen, I like to have aspirational goals and be working on big projects. I like the educational potential of this. I like the idea of a glowing plant. I’d like to own one. But scaring a lot of people causes a backlash and probably causes restrictive legislation. And if there is a problem, there will definitely be a backlash. The fact that it could cause a problem is a problem in itself.”
One of the concerns is the potential for the glowing Arabidopsis plants to cross-pollinate with other Arabidopsis plants — a possibility that thus far the Glowing Plant team has said won’t happen. But, according to Ohio State University ecology professor Allison Snow, the plants are capable of cross-pollinating; and, though Arabidopsis is not a “native” plant, it’s still found in many places across the United States. So despite the fact that the plants’ machinery may be weakened as a result of producing the glow, cross-pollination can’t be entirely ruled out. It’s also worth considering that the plants may be able to persist in the wild, at least at a low level.
Still, Snow said, perhaps the more important question is so what? “I haven’t thought of any harm that would come from it myself,” she said, stressing the fact that this is a much more philosophical battle about disrupting nature, although most things we release into nature do something to disrupt it. “Ecologically, I don’t know that it would be any worse than a streetlight — it would probably be way less bad than that.” However, she said she still hopes the Glowing Plant team does the necessary testing. “But I do think it sets precedent, and I’m not too happy about the precedent that it sets,” she concluded.
Perhaps somewhat surprisingly, the Glowing Plant team’s scientific advisor, Alameda-based bioinformaticist Patrik D’haeseleer, shares Snow’s concerns over precedent. “That’s exactly why I’m supporting this project, because it raises all these issues,” he said. “Listen, if we decide that it’s okay for a multibillion-dollar company to do this, then they’ve got to let us biohackers do it as well, right? My attitude is that there’s a chance we might get shut down by the EPA or the USDA, but in my opinion that’s not necessarily a bad outcome. If it helps clarify the regulatory framework around genetic engineering, that might be a good thing.”
This is a point that Taylor also emphasizes: Given the fact that the rules are clearly inadequate and have been exploited by large corporations for several years, now is a good time to evaluate what’s appropriate for the field of synthetic bio to make and release into the environment, and the sometimes insular community of DIY biologists should be a part of the conversation. Too much regulation would quash innovation, but too little is a black box whose implications are more opaque. But, given a list of actual environmental risks that government should be concerned with, D’haeseleer and Taylor argued, the Glowing Plant project would probably not be at the top.
And, according to Kuiken, the Glowing Plant project has forced people on Capitol Hill and in various federal agencies to finally take note of the gaping loopholes in the decades-old legislation regarding environmental release of genetically modified plants. The changes will take time, and “will most likely require congressional intervention,” Kuiken said, stressing that it will be a “politically difficult” challenge. But, the discussions are happening. “This project has really awoken a lot of people in Washington that they’re going to have to reevaluate how they’re going to examine a lot of these things.”
For Taylor, the Glowing Plant project has been a double-edged sword. Since the Kickstarter campaign ended, he’s now able to work on the glowing plants full-time, having quit both his day job teaching high school science and his after-hours classes at BioCurious.
But he said the schism the project created in the DIY bio community has been “frustrating, disappointing, and in some ways heartbreaking” — especially now that BioCurious board members haven’t let the team take their research materials to its new space. “I’m basically running under the assumption that the work we’ve done at BioCurious already is gone,” Taylor said. “It’s cleaner that way.”
The Glowing Plant project has impacted BioCurious in another way: It’s now struggling to keep afloat. Traditionally, the space has relied on membership fees, classes, and corporate sponsorships to cover its rent, insurance, and supply costs that total upwards of $5,000 to $6,000 per month. But perhaps it had become too reliant on Taylor teaching classes there; since he left, lab revenue has declined. Some members of the DIY bio community believe the Glowing Plant team “owes it” to BioCurious to help it financially.
The argument highlights an issue at the center of the whole Glowing Plant controversy: No one can seem to agree on what it means to be DIY in the first place. Philosophical arguments abound over the issues of patenting (some members believe fiercely in open source), funding sources, profit, and even broader existential goals. Are DIY bio labs platforms for education and creativity, or, as one recent Nature article put it, “hackubators” for entrepreneurial bubbling? A forthcoming DIY bio space in Oakland, Counter Culture Labs, hopes to be a site for all those things.
And, as the discussions around the Glowing Plant project continue, the verdict is still out on the goals of synthetic biology itself. A field currently buzzing with excitement over new possibilities for fighting disease and meeting our ever-increasing energy requirements may also occasionally be overzealous about its own capabilities. “I believe that we should be able to construct any genome that we like,” Drory declared at a technology conference sponsored by Google last year. “It’s obvious to me.”
It may not, however, be so obvious to everyone else. Drory’s statement, while hyperbolic, belies the view of many in the field. On the other side of the spectrum is a knee-jerk rejection of anything deemed as “tinkering with nature,” despite human civilization’s long history of doing so. But divorced from the raging debates over genetically modified organisms in our food supply, and in all likelihood posing no threat to the environment, the Glowing Plant project asks a more fundamental question: As far as engineering novel life forms, where do our values stand?
It’s telling that the American outlook of innocent until proven guilty — or, in this case, safe until proven harmful — has been countered in Europe by a precautionary approach. We as a society simply don’t know what to make of the fact that we could hold such power over our own biology. Chernobyl was a wake-up call for physicists; though a much longer way off, given the vagaries and immense complexity of biological life forms, synthetic biology could come with its own set of unintended consequences. The fact is, no one knows.
In the meantime, as crowd-funding platforms become a more popular venue for people with clever ideas to raise money, it’s worth asking what types of DIY bio projects will get funded in the future. Kickstarter is, after all, based on the premise that backers will get something in return. Thus, it’s easy to see how a novel product like a glowing plant might take precedence over an effort like finding an obscure gene implicated in an even more obscure disease. All it might take is a clip from Avatar and a packet of seeds to contain the promise of the boundlessness of science — unless we as a society can figure out what we’d like the future to look like in the first place. Right now, like Taylor’s Arabidopsis plant itself, there’s not much in the way of light.