Cathal Garvey used to work in cancer research. Now he is the scientific director of IndieBio, a biotech accelerator based in Cork, Ireland which is about to open a branch in San Francisco. Garvey originally studied genetics. “I got into genetics after seeing a documentary about it when it was quite young.” he says.”I had already decided that I was going to be a biologist at an even younger age. And then I thought ‘Oh my God, living things operate on a code.’”
After graduating, Garvey became interested in the DIYBio movement of amateur biotechnologists. “I started seeing all these people doing really exciting stuff,” he says. “They were just doing what they wanted to do. It was what I imagined I would do when I was going into college and what I imagined nobody ever got a chance to do when leaving college.” So Garvey quit cancer research, built a lab in his mother’s spare bedroom, and started to conduct biocoding experiments using his own open source tools.
DIYBio is the wetware equivalent of the maker movement: amateur biotechnologists tinkering with DNA using low-cost tools and an open source ethos. Synthetic biology, or biocoding as Garvey prefers to call it, is a subset of DIYBio, which views biological systems and organisms as technologies which can be engineered at the cellular and DNA levels. Biocoders don’t just want to use sequencing to determine the order of nucleotides within a DNA molecule but to synthesize entirely new molecules. Biocoding can be used to engineer organisms like bacteria and yeast to make everything from vegan cheese to new cancer therapies.
“This is a technology that changes the way we eat, the clothes that we wear, the environment that we breathe,” says Garvey. “It can undermine the inability of the existing pharma industry to provide the drugs that we need. They are not meeting some of our demands because they can’t with their technologies or their capital requirements. Synthetic biology could.”
IndieBio started life in summer 2014 at University College Cork, Ireland. Ireland is already a biotech hub and one of the world’s biggest exporters of pharmaceuticals. Six teams from all over the world spent three months in Cork manufacturing artificial milk for vegans, engineering yeast to produce THC for medicinal purposes, and even making flowers that change color throughout the day. Most of IndieBio’s first cohort of teams had strong backgrounds in the biological sciences (the technology for Revolution Bio’s chameleon flowers, for example, was first developed as part of a DARPA project to make plants that would change color when they encountered explosive residues). IndieBio San Francisco is likely to add many more software developers to the mix.
Ryan Bethencourt is a cofounder of Berkeley BioLabs and now program director at IndieBio San Francisco. “Almost 50% of the people that we have in the lab are developers, software engineers, electrical engineers,” he says. “Many developers get involved in this because they stumble across an interesting open source hardware project which is for biotech. Some of them learn bioinformatics and some of them actually want to get their hands dirty. They will build their own DNA sequence and then they can insert it into a new bacteria. “
The “Hello World” experiment of biocoding is glowing bacteria. First you need a chassis, a living cell that will host your new DNA. The E. coli bacterium and yeast are popular chassis since they are well understood and readily accept new genes. Select a fluorescent protein, generally from a firefly or jellyfish, in the color of your choice and order the DNA sequence for it. This sequence must be pasted into a plasmid, a circular DNA molecule which can replicate independently of chromosomal DNA. Essentially, you cut out part of the plasmid, paste in your fluorescent DNA sequence, and inject the plasmid into the E. coli. The bacteria manufactures the protein and starts to glow. With the right equipment and supplies, of the kind available at your friendly local biohacking space, you can do this experiment in under an hour.
Protocols, or step-by-step guides, are available online for many biocoding procedures like PCR (polymerase chain reaction). PCR replicates a DNA segment billions of times. It’s the same process used in every crime show to take a cheek swab from a suspect’s DNA and match it. “A protocol is a recipe for doing science,” says Bethencourt. “You position the gel as such, you warm the gel for x number of minutes. There’s nuance in it in the same way that you can be a good baker or a bad baker even when you follow the same recipe.”
Once they have learned the basics, and made some mistakes along the way, developers start to engineer their own biotechnology products. “I’ve seen everything from developing new types of fermented mushrooms to algae bio batteries that were printed by a biochemist,” says Bethencourt. “A computer scientist created cellulose. He took a bacteria and got it to grow a baking pan full of cellulose. When he dried it out it looks like parchment, so he basically made paper out of bacteria. So you just put in sugar and out comes paper.”
So far there aren’t many software tools available for making new DNA, as opposed to understanding existing DNA, but that is starting to change. Synbiota is a web-based groupware DNA design platform. “Think GitHub for biotechnology,” says Garvey.
Antha is a new open source high level language (based on the Go language) for biological experiments, which builds work flows from individually testable and reusable Antha Elements. An element can be anything from genetic elements such as a gene, transcription factor, or the particular strain of yeast or bacteria used as a chassis to an experimental procedure such as DNA assembly. Antha can be used to control existing lab equipment and capture experimental data automatically. “It’s hard to find a mental framework where using a computer to design the whole process makes sense, “says Garvey. “That’s why I am excited about Antha because I think they are very close to getting that right. ”
Biocoding is still considerably more messy than its software equivalent. “It can be quite frustrating,” says Garvey. “There’s no compiler. There’s no debug. Nothing drops to the command line when your program crashes. It’s hard, it takes time, it’s a challenge but it’s going to be a very rewarding challenge. Whoever gets into biocoding at this stage will be the people who shape it.”
There is one characteristic, however, which biocoding does have in common with software. It scales. “Every diabetic in the world today uses insulin produced by genetically modified yeast or bacteria,” says Garvey. “The cost of ordering the DNA for insulin is in the range of 200 EUR ($250). This is a technology that scales because every factory producing insulin, every cell of E. coli, can duplicate itself. In fact, it can’t stop duplicating itself without human intervention. If you want to make a mobile app that does something or an organism that does something, there are many occasions where you will find that it’s actually more straightforward and cheaper to do it with an organism.”
“If you look at manufacturing in biology the costs are often sugar water and that’s it,” says Bethencourt. “So if you are talking about a bacteria or yeast, clear sterile sugar water that goes in and hopefully out comes your product. It’s not expensive to get the basic equipment, maybe $1,000-2,000. If you have to buy newer equipment sometimes tens of thousands of dollars. Half a million dollars is enough to build a real biotech company.”
Garvey now wants to educate the next generation of biocoders. CoderDojo is a global network of over 500 volunteer-led, free programming clubs for kids aged 7-17, which also started in Cork. Garvey is currently recruiting kids from CoderDojo to participate in the first BioCoderDojo. CoderDojo places a lot of emphasis on peer-led learning. Once the kids reach a certain level of proficiency, they mainly teach each other. Since most kids have tablets and laptops, but won’t be familiar with lab equipment, the initial learning curve will be steeper for BioCoderDojo but its DIY ethos is the same.
“What we want is for these kids to come in and say ‘What you did was cool but I have a better idea’ and we actually support them in their own projects in the same way that CoderDojo does,“ says Garvey. “I want them to feel like this is something that is going to be very normal to your generation. Because that’s how it’s going to be.”