A Blog by Ed Yong

Can We Save the World by Remixing Life?

In 2011, a team of undergraduate students from Imperial College London devised a fresh way of halting the spread of deserts: Make bacteria that will persuade plants to grow more roots.

Drylands—areas that get little rain—cover around 40 percent of the Earth’s surface. They are already fragile places and a combination of drought, climate change, overgrazing, and unsustainable farming can finish off any plants precariously clinging to life there. Without roots to hold the soil together, wind and water erode the top layers, leaving only the infertile lower ones. In this way, more and more land transforms into barren desert with each passing year.

There are many possible ways of countering or preventing desertification but the Imperial team wanted to try something new. They added a set of genes to the gut microbe Escherichia coli that allow it to detect malate—a chemical released by plant roots. When placed in soil, the bacteria swim towards roots and gets taken up by the plant. Once inside, they use another second set of added genes to produce auxin, a hormone that stimulates the growth of roots. Longer roots mean more stable soil, which means less desertification.

Individually, the bacteria, genes and hormones are all found in nature. But it was the combination of these components that yielded a synthetic organism unlike anything seen before—a plant-tracking, root-making, soil-stabilising gut bug.

Remixing life

This project is just one example of synthetic biology, a growing field that brings engineering principles to the world of cells, genes and living things. It’s telling that the team described their creations in the lingo of engineers. They took genetic “parts” from a standardised registry, packaged them into different “modules” and shoved them into a bacterial “chassis”. Other scientists should be able to assemble the same parts in new combinations to do different jobs, just like Lego bricks.

Living things have been doing this for millions of years, borrowing “parts” from each other to survive in the world’s worst environmentsharness sunlight, snatch bodies, and destroy coffee. Synthetic biologists pull off similar tricks but with a dash of deliberate design. As in engineering, each part should have a specific purpose and its role in the whole should be predictable.

It’s grander in scope than most genetic modification, which involves modestly changing a few genes. By contrast, synthetic biologists work with large networks of genes to produce yeast that can brew antimalarial drugs instead of beer or cells that self-destruct if they turn cancerous. In his new book Creation, Adam Rutherford compares the field to the hip-hop scene of the 1970s, where DJs would start to create new music by mixing existing beats, riffs and lyrics. “Synthetic biology is remixing,” he wrote. “The ethos of this emergent scene is one of unprecedented and unbridled creativity.”

Take the root-making bacteria. It was the second-place winner of the 2011 iGEM (International Genetically Engineered Machine)—a vibrant talent competition where teams of undergrads design and build new genetic machines to solve a problem, using an inventory of standard “parts”. They have 10 weeks—it’s basically a summer project. While many college students spend similar projects on achingly dull menial tasks, the iGEM competitors tinker with biology before they even enter a PhD programme.

Two households, both alike in dignity

Chris Schoene, now at Oxford University, was part of the Imperial iGEM team and described their work at a conference at Cambridge, UK, entitled “How will synthetic biology and conservation shape the future of nature?” The meeting aimed to bridge these fields, which rarely talk but definitely should. Many of the mooted applications for synthetic biology have the potential to affect the planet for good or ill, from yeast engineered to make fuels, to plants modified to use resources more efficiently, to sensors that detect and break down pollutants.

But while both camps are often looking at the same problems, their outlooks are so different that tensions inevitably emerge. As conference organiser Kent Redford  from the Wildlife Conservation Society said, “Conservationists get more pessimistic when they drink, but synthetic biologists only get more optimistic.”

Synthetic biologists combine the brash hopefulness of people in a hot, growing field with the can-do attitudes of engineers. Like the iGEM competitors, they look for solutions and work backwards. But conservationists are facing huge and depressing challenges, and they’ve been burned by the unintended consequences of well-meaning solutions. Many hear “synthetic biology” and their minds race to creatures like cane toads and mongooses that were introduced to islands to deal with pests and ended up killing local wildlife instead. Or, as someone inevitably mentioned, Jurassic Park.

“It’s not like engineering a machine. If you make a really bad car, it won’t make itself,” said Steve Palumbi , an ecologist from Stanford University. If you make a mistake with a living thing, “you may be stuck with your ‘solution’ forever.”

Many of these concerns are longstanding ones, imported from debates over genetically modified organisms. Synthetic biology stands out if only for the complexity of its manipulations. Also, cheapening technology and the field’s free-spirited ethos mean that amateur “biohackers” now have the tools to run experiments in their garages or kitchens. As one delegate said, “There could be thousands of people making millions of invasive species.”

Adding known genes to well-studied microbes like E.coli, as the Imperial iGEM team did, is unlikely to have such dire consequences. But even then Paul Falkowski from Rutgers University noted that we have sequenced scores of microbial genomes, but still don’t know what 40 percent of the identified genes are doing. “We are monkeying with stuff we don’t really understand,” he says. “We say we’re going to invent a bug that will make a fuel and solve problems? It’s naive.”

Jim Haseloff, a synthetic biologist from the University of Cambridge who works on plants, understands the risks of introducing species into new environments (“I’m Australian!”). But he noted that possible harms are a given for any new technology. Focusing upon that ignores the fact that conservationists already face a dire uphill battle and need new solutions. “We’re living in an environment where we’re progressively eroding the natural environment—that’s the default,” he said. “Can we divert or deflect that harm?”

Peter Kareiva, chief scientist at the Nature Conservancy, adds that ecologists have learned from the lessons of the past. “Mongooses and Jurassic Park are old stories. Ecologists know not to release predators,” he says. By contrast, most modern invasive species are escapees from the pet and aquarium trade. Those are existing challenges that worry Kareiva more than any synthetic organisms might.

Still, risks exist, and Palumbi would be reassured if the synthetic biology community devoted as much creativity and cleverness into avoiding unintended consequences as it does into cool engineering fixes. “We want a culture where containment is as well-researched as creation,” he said.

Lego tigers. Credit: Stefan, via Flickr.
Lego tigers. Credit: Stefan, via Flickr.

Doing it right

Amid all the hype and hubris, the doom and gloom, Schoene’s root-making bacteria stood out as a tangible, grounded nexus for discussion. For starters, their goal seemed sensible. Jon Hoekstra from the World Wildlife Fund noted that the world has around 2 billion hectares of degraded land—an area the size of South America. Rehabilitating that land, either to create spaces where life can thrive or to grow crops that then don’t have to encroach on pristine spaces, is a goal that synthetic biology could realistically help with.

They were also wary of risks from the start and consulted extensively with biotech companies like Syngenta and environmental organisations like Greenpeace. Again and again, the same concern came up: Genes from the synthetic bugs might move into naturally occurring ones. Microbes, after all, can swap genes with tremendous ease, especially by exchanging mobile rings of DNA called plasmids.

So Schoene and his crew created a containment system called GeneGuard. They loaded their microbes with plasmids containing a toxin gene that kill the bacteria by making them literally split their sides. The only thing saving them is an antitoxin gene in the bacteria’s main genome. If the engineered bug passes its plasmid into a wild one, the recipient would make the toxin but not the anti-toxin, and self-destruct.

The team took steps to mitigate other risks. They chose to modify a gut bacterium rather than a more obvious soil-dweller like Bacillus subtilis because they didn’t want the engineered microbe to outcompete others in its environment. They consulted with ecologists who confirmed that the extra auxin wouldn’t cause problems if it leached into the soil, because it breaks down quickly outside a plant. They talked to the Berkeley Reafforestation Trust about how they might eventually piggyback off existing reforestation initiatives. And through panel discussions, they discussed whether the engineered bacteria could ever harm human health or hurt their plant partners.

“It’s a really nice example of not just solving a problem, but talking to people and finding out the issues that they’re concerned about,” said Keith Crandall, a geneticist from Brigham Young University. “That’s really the key— putting in safeguards that will satisfy the community.” The iGEM judges felt similarly, and specifically commended the team for being inclusive.

Plasters, panaceas and open doors

But the root-making bacteria also became a symbol for a different debate: Should synthetic biology play a role in conservation at all? Does it merely provide “sticking-plaster solutions” that seductively tackle some aspects of conservation problems, while distracting from more important issues. Desertification, for example, is largely caused by overgrazing. What will root-making bacteria do about that?

“The starting point of taking a tool and asking how it will solve a set of problems is putting the cart before the horse,” said Jim Thomas from The ETC group, a watchdog organisation looking at ecological aspects of new technologies. “Farmers already have other techniques to deal with desertification. The danger is that these inventive technological fixes might develop a halo as a way of dealing with the problem.”

“It would be hubristic to claim that the project was a panacea, but I didn’t hear anyone claim that,” countered Luke Alphey from the University of Oxford, who is developing genetically-modified mosquitoes to control dengue fever. “It would be equally hubristic to claim that these problems are so complex that no new technology could contribute to a solution.”

“It’s nowhere near perfect, and we haven’t been able to test it in a normal field, let alone in arid environments,” said Schoene. “It was a 10-week project.” Indeed, by the end of the competition, the team had tested the bacteria’s root-finding and auxin-making modules, but had not completed the GeneGuard. And since then, they have disbanded and started their own graduate programmes. The root-making bacteria are languishing in development limbo. Their legacy isn’t so much as a barricade for deserts, but as a symbol of tensions between a young hopeful discipline and an older weary one.

But they also show that tentative bridges are starting to form between the two communities. In 10 short weeks, the Imperial team focused on a relevant problem, carried out an incredible amount of engineering, took due heed of potential risks, and engaged with people from all sides. Perhaps, as one delegate suggested, if conservation biologists could take part in the next iGEM alongside synthetic biologists, they could infuse the competition and the discipline with their own values and priorities.

“You’re pushing against a huge open door, and I invite you to walk through,” said Paul Freemont, co-director of a synthetic biology centre at Imperial College London, to the assembled crowd. And with a smile: “And do please cheer up just a little bit.”

6 thoughts on “Can We Save the World by Remixing Life?

  1. “They loaded their microbes with plasmids containing a toxin gene that kill the bacteria by making them literally split their sides. The only thing saving them is an antitoxin gene in the bacteria’s main genome. If the engineered bug passes its plasmid into a wild one, the recipient would make the toxin but not the anti-toxin, and self-destruct.”

    A bit like the lycopene dependency and female-only population safety measures built into Jurassic Park’s dinosaurs, then? :)

  2. I would expect the real problem is that growing longer roots isn’t in the plants’ adaptive interest, or they would already have found that solution, so the plants will before long develop some way to get rid of the bacteria or at least the engineered effect. The people doing these things should probably read Darwinian Agriculture by Ford Denison. Not my field, but it seems very naive to think that organisms in the wild are going to “agree” with the intentions of engineers for very long.

  3. Darwinian Agriculture looks like a great book. I agree with Carl Zimmer: The phenomena of increasingly shady biotech innovation efforts at “saving the world” is “Increasingly disturbing”. But, I don’t know the context of his statement. And that’s the main problem with the titillating hopes of “saving the world” with biotechnology. Biotech engineers are ignoring the phenomenal importance of context to all life and ideas. What about encouraging a Pop Culture mythology that expresses the ingenious contributions of the single cell, and the innate empathy growing power of multilingualism? Encouraging these three holistic disciplines: Symbiosis in Microbiology, Multilingualism, and Mythology seem to have greater promise than bioengineering designers who take life out of context to save the world. If more people became multilingual like bacterium do with “quorum sensing” would they naturally share food and water more? If more people were consciously engaging their dreams with a more holistic biospheric mythology that did not swelter regional mythologies and cultures, would we all be more altruistic, fight less, work more collaboratively on avoiding meteorite impacts and other biospheric threats? The recent Presidential action of signing HR 933 shows the failure of politics to protect identity by increasing threats to context in a true democracy that unchecked biotechnology promotes against honest self protecting efforts such as the peoples initiative to require the labeling of GMOs, Initiative 522 in Washington State coming to vote this Nov 2013. Biotech firms generating “world saving” technology and then fighting concepts like labeling GMOs are a fundamental threat to free speech and free identity and to maintaining ecological “context” of “human nature” in a co-evolutionary life like poem. If GMO’s are so great they should want to label them; they should show their colorful plumage or their intimidating lions mane like the best of biology; explain how you relate and want to procreate like everything else.

  4. When GMOs first came into public prominence, I read that although the process where the genes of organisms are modified is called gene splicing — which brings up a vision of something very surgical, precise and discrete, like grafting part of one tree to another — the reality of the process is much less precise. In fact, it is more like firing a shotgun loaded with the gene that you wish to “splice” onto a gene sequence; it is not very precise at all.; the “spliced” gene can end up anywhere in the sequence. Additionally, we know that genes are much more than on off switches like bits in computer code; they effect each other in ways that we have yet to understand. Knowing that very simple organisms, like bacteria, swap genes and modify themselves at blinding speeds should be a red flag cautionary signal to any bioengineer who thinks that a bacteria, even with a “kill switch” to prevent it from spreading in the wild, can be contained. Remember, the swine flu model: pig infected with avian and human flu, both flus swap genes and voila!, you have an avian flu capable of infecting humans. Also, there’s that GMO corn that was supposed to be containable and has migrated — wind-born or carried by birds — to neighboring fields that were supposed to be protected from it. There needs to be a really, really long lead time from lab to real world on these things with stringent oversight and public commentary to make sure that this promise of scientific gold doesn’t turn out to be pyrite.

  5. this area is fascinating but the problem with these type of technofixes are the unintended consequences that often end up worsening the situation in the long term.
    take the yeast that brews anti-malarials as an example. this sounds like a brilliant solution until you look at the wider context. Artemesin for anti-malarials is currently grown by thousands of small-scale farmers in africa and asia, and more than enough artemesin is already being produced. These farmers now look likely to lose their entire market and may face destitution. the guardian has an indepth article on this at http://www.guardian.co.uk/global-development/poverty-matters/2013/apr/12/synthetic-malaria-compound-artemisia-farmers?CMP=twt_gu.
    You may think – well at least more land is freed up for food production – but it isn’t that simple. The engineered yeast needs sugar as a precursor, which also needs to be grown. In addition, the sugar industry is notorious for bad environmental and labour practices. So it looks like the long term effect of this synthetic artemesin will be to impoverish small scale farmers and increase the power of large agribusiness, while increasing environmental degradation. And to no real end, as there is already enough artemesin being produced by the farmers. There is a similar scenario on the verge of happening with vanilla farmers, as Evolva is planning on commercialising a vanilla produced by engineered yeast.
    There is a real need for the wider consequences to be properly considered before these synthetic biology projects go ahead. There is an alarmingly glib attitude that scientists often seem to have, but this technology is too powerful for that attitude to do. Is there any way of getting them to engage more deeply with the context of their interventions?

    [Joyg, thanks for the measured and thoughtful comment. Getting the synthetic biologists to hear these concerns was indeed one of the points of the conference and I think some headway was made there. The issues you mention about the artemisinin-making yeast were discussed, and I think specifics like that were far more impactful than hand-waving “Oh it’s unnatural and, oh dear, Jurassic Park.” People were listening. – Ed]

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