Written for Spring 2012 issue of I, Science magazine.
In May 2010, the J Craig Venter Institute held a press conference to announce the creation of a synthetic bacterial species. After 15 years of work, Craig Venter’s team, led by Nobel laureate Hamilton Smith, managed to synthesise the entire genome of a bacterium and insert it into a recipient cell. “This is the first self-replicating species we’ve had on the planet whose parent is a computer”, said Venter. “It’s also the first species to have its own website encoded in its genetic code.”
When Venter had described the sequence of technical breakthroughs leading to this result – transplanting a chromosome from one bacterium to another, synthesising the Mycoplasma genitalium genome, growing artificial chromosomes in yeast, adding ‘watermarks’ such as a web address to synthetic DNA to make it distinguishable from naturally-contaminated DNA – there was a single question from the crowd of reporters. “Could you explain, in laymen’s terms, how significant a breakthrough this is?”
It’s a question I put to Dr Tom Ellis, a synthetic biologist from Imperial College London’s Department of Bioengineering. For him, biological science and biotechnology are turning into an information science. “Think of the human genome as a vast amount of data”, he says. “Now we’re sequencing the genome of a new organism almost every day.” Admittedly, these are mostly bacteria with relatively small genomes, but the amount of data appearing is still staggering. “Biology is now an information-rich subject”, says Ellis. “Really information rich.”
Unsurprisingly, the common analogy is one of computation. “One of the major tenets of synthetic genomics”, says Smith in Creating Synthetic Life, a documentary made for the Discovery Channel, “is that the genome, the chromosome of the cell, is the software – the operating system of the cell – and the cytoplasm is simply the hardware that allows a genome to express itself.” The computational analogy can only be pushed so far, since DNA itself – the software – is physical: “You’ve got an operating system which is also part of the hardware”, Ellis notes. But it’s compelling, nonetheless.
“Synthetic biology is building new subroutines to run on the operating system”, he says. Slightly adapting Smith’s metaphor, we can put these subroutines in a more familiar context by thinking of them as apps, with the cell as a phone and the genome as an operating system such as iOS or Android. These apps are currently modest constructions, but researchers are “building up to entire programs that you can load and even subroutines that can then be engineered to run within those programs”, he says. “We’re getting up to that sort of complexity now.”
“The majority of synthetic biologists are working on the design of effectively small software apps that will boot up and run within the genome”, says Ellis. “What Venter showed is that all the materials are there to be able to write the entire operating system.” But, importantly, he didn’t rewrite it from scratch. Imagine a hacker copies the code for an operating system and adds something at the end – perhaps just a comment with her name. “That’s what Venter’s done – copied the entire genome and in just a few places put watermarks to say this isn’t the original one, this is the one with our change”, he says. “Do they understand the program, the operating system? Not really. Not yet. But they want to.”
Many institutions are working towards standardisation – in terms of data, how specific biological parts should be defined, and how parts are measured – that will bring an even greater level of engineering maturity to the field. “At the moment the computing analogies function to galvanise people into action,” says Dr Darren Nesbeth of University College London’s Biochemical Engineering Department. “Right now, most biological labs in the world pretty much do things in a bespoke manner. If people constructed biological devices using the same standardised language, then there are benefits to that in terms of what people can do.”
Standardisation will further support the establishment of repositories of biological components such as the BioBricks Foundation, which maintains a catalogue of parts and devices. “Hopefully, we’ll get to the stage where you can have an algorithm which tells you all of the rules for where things should go if you build up an entire genome from scratch”, Ellis says. “And then from that point, someone like Venter could sit down with the parts list he wants and create a cell that had a completely synthesised genome based just on parts.”
“The actual definition of synthetic biology is quite hard to pin down”, he tells me. “But the simplest way you could put it is that it’s about applying engineering principles to biology.” The more I think about what this prosaic statement actually means, the more I’m struck by its audacity.
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