(Image: Paul Wearing)
Would Like To Meet: Someone with verve and youthful optimism; a risk-taker who believes they can change the world for the better. Me? A little jaded, I suppose. Age? Oh, I wouldn鈥檛 like to say, but old enough to have been burned a few times.
And so a blind date was arranged. Both parties were unsure what to expect yet sufficiently intrigued to show up. For a few days in April, a group of conservationists and a group of synthetic biologists . The idea was to get to know each other a little better and see if techniques from synthetic biology could help solve some of the most intractable problems that conservationists have been wrestling with for decades.
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It was a bold idea. You could hardly find two more ill-matched scientific disciplines. Synthetic biology is barely a decade old and driven by excited young people who believe they can literally re-engineer the world by creating new and improved life forms from tailor-made building blocks. Conservation is a mature field, facing huge problems and desperate for new ideas. 鈥淲e are watching species disappear but we only know how to wring our hands, scream from the rooftops about how bad humans are, and make you put plastic booties on when you come visit these animals,鈥� said independent conservationist and meeting organiser , to the synthetic biologists. 鈥淧erhaps you can help us figure out what to do.鈥�
Could synthetic biology be the boost conservationists need, or are the two simply incompatible? To answer that question, first let鈥檚 get to know the tentative daters a little better.
Synthetic biologists apply the principles of engineering, specifically electrical engineering, to biological components to create what are effectively living machines designed with a particular purpose in mind. Proteins and gene sequences are to a synthetic biologist what light bulbs and diodes are to an electrical engineer; bacteria and yeast cells, the chassis into which they place their customised gene circuits. Whereas traditional genetic engineering might involve transferring a gene from one organism to another and hoping it will do what it is supposed to, synthetic biology is about designing organisms to solve specific problems. It entails a more precise level of control: as well as inserting a gene you are also tinkering with cellular machinery that governs when and how much of that gene gets expressed.
鈥淚t is a very creative, design-orientated field,鈥� says , co-director of the Centre for Synthetic Biology and Innovation at Imperial College London (ICL). 鈥淎 lot of the excitement of it is that it鈥檚 driven by real applications.鈥�
One of the reasons conservationists like Redford think synthetic biology might be able to help them is that conservation has had some success with genetic engineering in the past. In the 19th century, American chestnut trees were a common sight in the eastern US. But by the early 20th century, 3 billon of these 30-metre-tall behemoths had been reduced to sorry stumps by a fungal blight imported on Asian chestnut trees. Then, about 20 years ago, someone had the bright idea of giving the American chestnut a wheat gene that breaks down the toxin produced by the fungus. The project has since been widely hailed as a success and the hope is that if the modified trees get regulatory approval for release, they will be introduced to the wild for the first time in a small field trial in the Appalachians.
If genetic engineering can help with this relatively simple problem, perhaps synthetic biology, with its novel tools, could one day help with some of the more complex issues that keep conservationists awake at night. And boy, there are a lot. The wish list presented at the meeting includes: designing high-yield crops in the hope that more land can be left uncultivated; tackling invasive species; finding alternatives to meat; creating safe, targeted pesticides; making endangered species less vulnerable to extinction as a result of climate change or infectious disease; and thinking up novel ways to satisfy our demand for ivory and other animal products without harming elephants, rhinos and the like.
鈥淭he wish list includes tackling invasive species, finding alternatives to meat and creating safe, targeted pesticides鈥�
Laid out like this, the gap between conservationists鈥� hopes and reality seems more like a gulf. Synthetic biology has achieved a lot since around the turn of the millennium but it is not yet capable of solving any of these problems. In fact, the field is still laying down its foundational technologies, building up the tools to allow the efficient design, construction and testing of its creations. The focus is on designing the biological equivalent of logic gates and transistors, and creating a library of standardised, reliable biological parts, or BioBricks, that people can order online.
To date, any applications have understandably been focused where the money is 鈥� biofuels and chemicals production. Conservationists are not fond of these industries because they tend to eat up vast swathes of land and generate new pollution risks. But there are some green shoots appearing. Some synthetic biologists are at least thinking in terms of environmental issues, if not conservation per se.
The annual International Genetically Engineered Machines competition () is the main event in the calendar for synthetic biologists. In 2011, second prize went to a group of undergraduates from ICL, who decided to tackle the growing problem of desertification. One major cause is the loss of the top layer of soil due to deforestation or poor farming practices. The team members reasoned that they could lessen this erosion if they could anchor that soil in place by boosting the root networks of any plants that did remain.
Their solution was to create a new organism using the gut microbe E. coli as the chassis and inserting genes from three bacteria, one to produce a growth hormone and two to sniff out chemicals normally produced by plant roots. Now they had a microbe that was attracted towards roots, where it could be absorbed and would then secrete a hormone to boost root growth.
Solving the problem of plastic pollution in the world鈥檚 oceans is another project with lofty environmental ambitions that started life at iGEM. Half of all the pollution in the world鈥檚 oceans is plastic, often in the form of tiny particles that poison marine creatures and accumulate in the food chain. A team led by Yanika Borg and James Rutley at University College London spliced genes into an E. coli chassis that would enable the bacterium to detect microscopic plastic particles and break them down, while surviving the high salt levels found in seawater.
Students unburdened by notions of financial reality tend to have the most ambitious ideas, but they are by no means the only ones thinking along these lines. group at the University of Oxford has its sights on Striga, a parasitic weed that costs farmers in Africa $10 billion a year in lost crops. They have modified baker鈥檚 yeast to produce a plant hormone that tricks Striga into germinating prematurely so that it dies before any crops are planted. Such 鈥渟uicidal germination鈥� is not a new idea but until now, nobody has been able to produce the plant hormone cheaply enough to help subsistence farmers in Africa.
Low-hanging fruit
If improving the productivity of farmland is one low-hanging fruit on the conservationists鈥� wish list, restoring polluted areas could be another. Freemont鈥檚 team has developed bacterial sensors that detect whether water contains arsenic or the parasite that causes schistosomiasis. Freemont says it would not be hard to build biosensors that detect specific pollutants 鈥� the first step to cleaning them up.
But even if more synthetic biologists take up Redford鈥檚 call to arms, there is still an elephant lurking in the room. Most of the items on the conservation wish list would require synthetic organisms to be released into the wild, where they could, in theory, out-compete their non-modified counterparts or evolve in unpredictable ways. Synthetic DNA could also be transferred to other organisms: microbes regularly swap stretches of DNA, and genetic information could then be passed on to more complex species via viruses. So far, there has been no substantial release of a synthetic organism into the wild but, understandably, the potential risks scare the hell out of conservationists.
Many synthetic biologists say that their creations would not, in fact, last long on their own. Nonetheless, to reduce the chances of synthetic genetic material escaping, they build safeguards into their designs. Some organisms rely on a specific nutrient or chemical to function 鈥� once it runs out, they perish. Kill switches, which make the organism self-destruct, are also popular. These become activated when a certain threshold, such as temperature or glucose level, is reached. But neither method is foolproof, as there is always the chance that the environment will contain a trace of the key nutrient or that the organism will evolve resistance to the trigger designed to kill it. 鈥淓volution is a really persistent, dogged force, so if there鈥檚 a way to weasel out of a containment strategy, ,鈥� says ecologist at Stanford University in California. 鈥淎nd if you鈥檙e talking about microbes, that 鈥榚ventually鈥� will not be very long.鈥�
To really ensure that a synthetic organism cannot interact with its natural counterparts, you need to engineer it to talk a completely different language. One way to do this is to create a new genetic code that does not occur in nature, which is exactly what and his team at the MRC Laboratory of Molecular Biology in Cambridge, UK, have done. By altering or substituting the sugars that make up the backbones of the DNA double helix they have created six 鈥渁lien DNAs鈥� or xeno-nucleic acids (XNAs). A modified gene created with XNA rather than DNA contains a 鈥渄ouble firewall鈥�, says Holliger. Not only does the machinery in a natural cell lack the capability to read the XNA, but also, because XNA does not exist in nature, if the synthetic cell is to survive, it has to be added as a kind of nutrient. 鈥淭he moment you withdraw that nutrient, the system withers and dies,鈥� he says.
Even if synthetic biologists can solve the problem of bio-containment, conservationists have other worries. At the meeting they expressed concern about a future controlled by biotech companies and unauthorised releases by rogue scientists. They were also wary of synthetic biology being used as a convenient quick fix, rather than the harder task of changing people鈥檚 behaviour. But there was enthusiasm, too, at the prospect of getting involved in a field that is still in its infancy. 鈥淢y guard is up but I鈥檓 ready to listen,鈥� says zoologist Tony Whitten of the University of Cambridge.
鈥淚 think the science will happen,鈥� says Freemont. The synthetic biologists are certainly confident in their technical capabilities, but they realise that public perception could be a problem. 鈥淚f synthetic biology is to have some kind of role in environmental applications, society has to want it to,鈥� Freemont says. The opposition to genetically modified crops, particularly in Europe, suggests that this is a big hurdle. 鈥淚n principle, I think it鈥檚 an excellent area of research for us to explore but we must do it in conversation with the regulatory people.鈥�
鈥淭he synthetic biologists are confident of their technical capabilities, but they realise that public perception is a problem鈥�
Who鈥檚 going to pay?
On a practical note, everyone at the meeting recognised that there can be no collaboration without funding. Unfortunately, saving animals and ecosystems does not attract the dollars in the way that biofuels, chemicals or pharmaceuticals do. But synthetic biologist Drew Endy of Stanford University had an idea. He suggested that conservationists could use their expertise to help invent a new technology for bio-containment. 鈥淚f you patent something that every synthetic biologist has to use in order to carry out their work, you could get money for conservation and conservationists could be gatekeepers for synthetic biology,鈥� he told the meeting.
Another idea is that ambitious plans to bring extinct species such as the mammoth and Tasmanian tiger back to life could help bankroll synthetic biology鈥檚 foray into conservation. If successful, the money people will pay to see these resurrected species could be used to fund research on a list of conservation problems. Others, however, see the de-extinction work as a distraction rather than a potential source of funding.
Like any new relationship, the parties involved aren鈥檛 quite sure how this one will develop. Synthetic biologists seem excited by the prospect of novel challenges. And having met the newbie, conservationists still seem keen to give it a go. Since the April conference, more dates have been arranged: Redford was invited to talk at , the annual get-together of synthetic biologists, which happened in July.
Conservationists also now realise that, even if they are prepared to take on all the baggage associated with synthetic biology, a successful partnership will not provide the solutions they are praying for any time soon. Still, if both parties start thinking about each other a little more, some interesting collaborations are likely. And if that promise helps jaded conservationists get up in the morning, then surely the blind date was worth it.
This article appeared in print under the headline 鈥淭he odd couple鈥�
