Engineering Life

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.

See Your Favourite Acts, Discover New Ones

Interview with TEDxImperialCollege host Gareth Mitchell.

“This is turning out to be my fantasy dinner party,” says our TEDxImperialCollege host Gareth Mitchell as he looks through the list of speakers. “These have been an exciting few weeks. Every few days, the organising committee has been adding new speakers to the line up. Just look at the disciplines covered here: engineering, computing, art, green energy, entrepreneurship, development, neurotechnology, neuroscience (yes there IS a difference and I look forward to exploring that over a cup of tea!), music, fashion, design, and support for offenders.”

As well as being a lecturer in Science Communication at Imperial College, Gareth also presents Click – the BBC World Service radio show covering engineering and technology – and regularly contributes to BBC Focus magazine. As he puts it himself, his geek tendencies go back to a childhood spent playing with electronics, and as a science communicator he’s clearly relishing the prospect of hosting such an eclectic set of talks.

“There will be no ghettos here: just amazing, unexpected conversations both within and outside the sessions,” he says. “I am familiar with some of the speakers already but there are others who I’ll get to know for the first time. It reminds me of music festivals where the joy of seeing your favourite acts is matched only by that of discovering new ones for the first time.”

And just as the experience of seeing a band at Glastonbury is made richer by the atmosphere and heritage of the place, so too with TEDxImperialCollege: “One really feels the spirit of the Great Exhibition around these parts. South Kensington exudes the feeling of a place that’s been a home to science, culture and exploration for the last century and a half.”

“As for me, on the day I’ll do my thing: usher people on, usher them off, do the intros, make sure everyone’s happy and politely pester the speakers if they run over time. But most of all, I’m going to sit back, listen and soak it all in. See you there!”

Polydactyl Kittens with Multiple Mittens

Written on 11 January for The Dog & Pony Show, my I, Science blog.

Welcome to The Dog & Pony Show! Let’s talk about cats.

Not all cats are created equal. A couple of days ago, the BBC posted an article about a pair of polydactyl kittens. (If you’re wildly picturing a chimera of cat and pterosaur, you’ve headed off in the wrong direction. Come back.) Polydactyly is an anatomical anomaly in which a hand or foot (or paw) has more than the usual number of digits – which is of course five for humans, but five on the front feet, including the dewclaw, and only four on the back for cats. Occasionally, the extra digits can form an entire sub-paw.

Polydactyly appears to be both a relatively common condition in cats – or at least certain breeds of cat – and a relatively common source of news for the BBC: links to two other stories about cats with supernumerary toes accompany the latest post. This week’s kittens, Ned and Fred, have an extra eight and 10 toes, respectively. Last month an entrepreneurial cat named Daniel, from Wisconsin, USA, put his 28 toes to good use by getting people to donate a dollar per toe in a fundraiser for a local animal rescue centre.

Henry VIII’s second wife, Anne Boleyn, is rumoured to have had an extra digit. But this is probably due to an unflattering description written 50 years after her death by the C16th propagandist Nicholas Sanders, a man as influential as he was unreliable: “It is said she had a projecting tooth under the upper lip, and on her right hand six fingers. There was a large wen under her chin, and therefore to hide its ugliness she wore a high dress covering her throat”. Sanders does not paint a pretty picture.

In cats though, an extra toe on each front foot often gives the cute impression of thumbs – as with this adorable little gremlin – and there are many polydactyl-cat enthusiasts. Ernest Hemingway was a fan and his former home in Florida is now a museum of sorts and home to about 50 cats, half of which are polydactyl and all descended from cats belonging to the writer. Indeed, polydactyl cats are occasionally referred to as ‘Hemingway cats’.

As Hemingway’s legacy suggests, though polydactyly can occur by itself, it more commonly appears as a congenital anomaly, inherited as an autosomal single dominant trait of the Pd gene. This, and the observation that the east coast of North America centred around Boston has an especially high proportion of polydactyl cats, has led to the idea that most, if not all, of these cats are descendants of extra-toed cats brought over on ships from the UK – apparently because they were considered lucky by sailors. (In other parts of Europe, polydactyl cats were largely wiped out – apparently because they were considered unlucky by everyone else.)

The Straight Dope tells me that an article in Cornell University’s Cat Watch in 1998 looked at studies that suggested the polydactyl trait may indeed be traceable to cats arriving in Boston by ship. But we’ll have to set that against a 2008 study by geneticists who found that the polydactyly in the cats they looked at in the US and in the UK can be caused by different genetic mutations, suggesting that the extra toes originated in more than one place independently.

Whatever its origin, polydactyl cats are now being bred in the US to preserve the trait. Once barred from cat shows, breeds such as the Polydactyl Maine Coon are now recognised by TICA (The International Cat Association) and a New Traits class introduced to official shows to cater for them. To get a polydactyl kitten you just need one of the parents to carry the trait, making it relatively easy to select for. The only problem for the cat – except in extreme cases, where too many toes can impair mobility – is that untrimmed extra claws might twist and dig into the skin. Odd as a six-toed cat may sound, it’s certainly no stranger than selecting for squashed noses or baldness.