Welcome to Gene Club: underground genome editing

Tools like CRISPR are allowing anyone to alter DNA – even amateurs. Who are they, and what are they up to? JV Chamary meets the biohackers...

5th January 2016
Welcome to Gene Club: underground genome editing (JV Chamary/BBC Focus Magazine)

Within a tiny room in a north London basement, Ilya Levantis opens a tupperware containing what looks like a leftover takeaway. “Fashion designers these days get interested in this stuff,” he says, proudly showing off a rubbery pancake in a brown liquid.

The “stuff” is kombucha, which is used to make fermented tea. It’s produced by a colony of microbes, the most important being Gluconacetobacter, which secretes strands of cellulose. Unlike material made by plants, a kombucha pancake is almost pure cellulose. When thin, it can be dried for paper, and used in wound dressings and high-end speaker cones. When thick, it’s tough enough for clothing. “Some people call it vegan leather,” says Levantis, a 25-year-old graduate who works in bioinformatics. He can now do genetic engineering as a hobby.

Levantis is director of Biohackspace, a laboratory that’s half the size of a garage in the London Hackspace – a building located, aptly enough, in Hackney. Some of the lab’s equipment was built using tools from the nearby electronics, woodwork and metalwork workshops, while other kit was donated by universities.

Biohackspace contains a PCR (polymerase chain reaction) machine that’s used for amplifying DNA samples, shelves of chemical reagents and a fridge full of Petri dishes – all the things you’ll find in a typical molecular biology laboratory.

Except the lab doesn’t cater for professionals, but amateurs. In March this year the UK Health and Safety Executive (HSE) registered Biohackspace as ‘GM Centre 3266’ – the first lab in the country that allows anyone to try their hand at genetic engineering.

Reagents used for growing cells include vinegar and seawater
Reagents used for growing cells include vinegar and seawater

Although many of us think ‘hacker’ means a person who breaks things (technically, that’s a ‘cracker’), the word more properly applies to people who make or repurpose things, especially those who tinker with technology. ‘Biohackers’ play with biotechnology and form part of the Do-It-Yourself biology movement.

DIY bio groups are run by volunteers, and members usually pay a monthly fee to cover the costs of facilities and supplies for a shared lab, which provides affordable access to anyone curious about biology. In 2010, there were only a handful of biohacking labs; according to diybio.org, there are now over 60 local groups around the world. While groups generally start as ‘garage biology’, others – like BioCurious in California – have become larger.

Britain’s biohackers

London’s Biohackspace currently has about 20 regular members from various backgrounds, ranging from artists to engineers. Most have no scientific training. Lena Asai, a design student at Goldsmiths, University of London, got interested after seeing biology-inspired art at a museum in her native Japan, where a scientist suggested she find a community lab. That led her to Biohackspace.

“They didn’t know what to do with me in the beginning,” explains Asai. “The first thing I said was, ‘I want to play around with DNA and stuff’. Obviously I didn’t know anything back then!” She has since attended a bootcamp at University College London (UCL) to learn basic genetic modification techniques. Her goal is to bring scientists and artists together. “We’re not doing science just for fun,” she says. “A communal lab is a great place where we should initiate collaboration.”

A thin sheet of dried kombucha produces strong paper
A thin sheet of dried kombucha produces strong paper

One of Biohackspace’s collaborations involves the kombucha pancakes grown by Levantis. The liquid has added vinegar – to lower the pH for acidic culture conditions – plus food in the form of sugar, which can come from fruit juice. The team at Biohackspace wants to use the kombucha in a 3D-printing project called ‘JuicyPrint’. While many 3D printers squeeze melted resin from a tube, depositing layers that turn solid after exposure to UV, JuicyPrint would use bacteria genetically-engineered to only produce layers of cellulose when blue light is shone on them.

Another project is a ‘DIY Beer Kit’, which aims to draw attention to hacking by exploiting the trend for home brewing. The kit includes a pick-and-mix of yeast strains, each genetically modified to make molecules that offer weird and wonderful flavours. Biohackspace entered its DIY Brew Kit in the 2015 International Genetically Engineered Machine (iGEM) competition, where it won a Bronze medal.

DIY bio and iGEM are closely linked to synthetic biology, which involves building living machines from a set of standard parts – genetic Lego blocks called BioBricks. This requires a toolkit, and the most powerful new technique in molecular biology is the CRISPR-Cas9 system, known as ‘CRISPR’.

What is CRISPR?

CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) are sequences of DNA letters, first discovered in E. coli in 1987. A decade later, researchers revealed that CRISPRs form part of an anti-viral defence system used by bacteria and other microbes: after a virus invades a cell, enzymes cut and paste bits of the viral genome between CRISPR sequences in the cell’s DNA. This leaves a genetic memory for an RNA ‘guide’ that an enzyme called ‘Cas9’ uses to recognise and destroy viral DNA, should an invader return. In 2012, bioengineers showed that the RNA guide could be reprogrammed to target any DNA sequence.

Unlike most gene-editing techniques, CRISPR is revolutionary because the technology is precise. It’s also quick, cheap and easy to use – so simple that even amateurs can use it.

Johan Sosa, an IT consultant and member of hacking group BioCurious, is already experimenting. “Currently we’re creating the guide RNA that we’re going to use to edit a yeast genome,” he says. One possible application is the ‘Real Vegan Cheese’ project, which aims to modify baker’s yeast so it produces milk proteins.

What is CRISPR? What is CRISPR? What is CRISPR? What is CRISPR?

Scientists design a ‘CRISPR’ made from RNA. It includes a series of letters that matches a unique 
DNA sequence within an organism’s genome.

The CRISPR molecule is attached to ‘Cas9’ (shown here in beige). This is an enzyme that uses its RNA ‘guide’ to recognise the target DNA sequence.

The CRISPR-Cas9 tool cuts the strands of the target DNA’s double helix, then the cell’s repair machinery will fix the damage – minus the old DNA sequence.

The CRISPR technique can be used to delete unwanted DNA, or to find and replace a sequence by adding genetic material – such as a new gene.

 

PLAYING SAFE

Anyone who tinkers with nature can be accused of ‘playing God’. And given that some people are wary of genetic modification by professional scientists, it’s understandable that some might worry about amateurs meddling with organisms they don’t understand. But even with CRISPR, we shouldn’t overestimate what biohackers are capable of.

“CRISPR is merely a tool – you still have to have an idea of what genes you want to turn on and off,” explains Dr Darren Nesbeth, a synthetic biologist at UCL. “Knowledge itself is the biggest barrier to being able to redesign a cell.”

Prototype cell-washing machine (left) for removing salt so bacteria accept new DNA, and two bioreactors (right) for making biofuels etc
Prototype cell-washing machine (left) for removing salt so bacteria accept new DNA, and two bioreactors (right) for making biofuels etc

Biohacking is also limited by the resources available to a typical DIY bio lab. Reagents such as enzymes can be expensive, and companies that manufacture CRISPR sequences have safeguards to ensure they don’t supply potentially malicious genetic material. “Somebody can’t order the sequence to build the Ebola virus,” says Maria Chavez, Director of Community at BioCurious. “Nobody is going to sell you those genes.”

Objections to biohacking are similar to arguments in the GM debate, which discuss hypothetical scenarios such as strains escaping, or terrorists designing weapons. Nonetheless, DIY bio groups take it seriously. US government agencies like the FBI and Department of Defense keep in touch and send agents to visit labs. “At the beginning they were coming through quite frequently – at least once a month, formally,” says Chavez. “Informally, I’m not sure how many times they may have dropped in.”

DIY bio groups also have rules for what their members can work with. BioCurious labs are classified at biohazard safety level-1 (BSL-1), which means no projects using mammalian cells. At Biohackspace, no pathogens are allowed. “They’ve got a licence now from the HSE to do genetic modification, which requires they have a safety panel of individuals,” says Nesbeth, one of the group’s advisers. “There’s a framework and guidance there equivalent to what happens at a university.”

CITIZEN SCIENCE

Research has traditionally followed two routes – academic and industrial – but hobbyists could provide a third way. Such citizen science involves freedom from responsibilities such as teaching and writing scientific papers. It also offers a nice environment for brainstorming, but such blue-sky thinking is less tethered in reality, says Nesbeth. At Biohackspace meetings, he tries to bring members back down to Earth without being too negative. “So you have to avoid just being there to be a party-pooper and saying, ‘Well, this will take millions of pounds,’ or ‘Actually, that will take 10 years’.”

Biohackspace director Ilya Levantis (far right) discussing future plans with artist Lena Asai (centre) and other lab members
Biohackspace director Ilya Levantis (far right) discussing future plans with artist Lena Asai (centre) and other lab members

Nesbeth supervises UCL’s iGEM teams and studies industrial applications for synthetic cells, such as manufacturing drugs and biofuels. He believes the biggest impact could be on altering the perception that genetic engineering is only done by academics in an ivory tower. “I see it as a route to demystifying science for the general public,” he says. Anyone can sign up to join their local biohacking lab.

At the end of Biohackspace’s weekly Wednesday night meeting, several members take away sandwich bags containing kombucha to grow at home. Levantis mentions that because more people are getting involved in DIY biohacking, the lab now needs to expand beyond a basement in Hackney, a location which also makes it seem a bit hipster-ish.

“It’s literally underground,” Levantis jokes. “Our goal for the next lab is to 
have windows.”


JV Chamary is a biologist and a writer. His latest book is 50 Biology Ideas You Really Need To Know

This article first appeared in the December 2015 issue of BBC Focus Magazine.

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