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Gene Genie

Meet Barry Canton. Barry works in a dull-looking warehouse on the Boston shipyards. It’s beside a large dry dock where they raise cruise liners from the water to scrape off barnacles and repaint their undersides.

On the opposite side of the dry dock is a tatty warehouse built by the US military. Its lifts are strong enough to take Humm-Vees to the fifth floor, but all it houses nowadays are artists and artisans, who unwittingly look across the dock at part of America’s energy revolution. Unassuming Barry from Sutton is part of a group of dockland geeks who could revolutionise fuel production for the coming century.

Barry, his wife, their lecturer and a few fellow college classmates left MIT two years ago to start their own business, Ginkgo Bioworks, named after a rare plant classed as a living fossil. At the time there were plenty of research businesses going belly-up, and broke scientists were offloading lots of usable but unsaleable equipment. So Barry and his team did some scientific skip-diving, grabbing equipment for free or for cheap and fixing what need to be fixed to equip their lab. They fitted out their premises largely with orphaned machines, carted out the back door of college labs, and quietly went to work.

Two years later, things are a little different. US Vice-President Joe Biden has just cut a $6million cheque made out to Barry, his team and their collaborators to develop a new fuel from genetically-modified bacteria. That’s some good recycling.

Their work is, publicly, much-maligned stuff. The Ginkgo team deal in Franken-science, DNA-tinkering, injecting genetic material into a nasty little bacteria that most people treat with heavy doses of bleach spray. The modified E-Coli organisms that Ginkgo produce do not do what regular bacteria do. They emit fragrances, flavourings, and now a fuel that you can pour straight into the petrol tank of your car. Barry’s team are making a bacteria that ‘eats’ Carbon Dioxide and ‘poops’ a clean, lead-free, sulphur-free petrol.  And they have plans for much more. Their collaborators are working on bacteria that make foodstuffs. Bacteria that produce malaria drugs. Bacteria that kill cancer cells.

Of course, you’ve never heard anything about this Dublin-born scientist because, despite pitching the story widely to Irish newspapers, no-one wanted, or had the budget this feature. But it’s a story worth telling. So here it is, as it could have been, below the fold.

But for now, and for the team at Ginkgo, it’s all about petrol.

Giving Bacteria a Case of Gas

Says Canton: “We figured out a way to use E.Coli to accept hydrogen and CO2 as inputs and convert those into iso-octane which can go right into the gas tank of your car.
“We think we can make it pretty easily. It’s a very good fuel, and it’s relatively good in terms of its anti-knock capabilities. We’re creating a hydrocarbon, so burning that isooctane will be cleaner than other fossil fuels because it will be sulphur-free and nitrogen free, more similar to burning methane.
“It will be releasing CO2, but we’re also consuming CO2 when we make it, so in theory the whole system shoud be carbon-neutral.”

He makes it sound simple, but building enough DNA to programme a bacteria is not like worming a dog. It is an extremely elaborate process, for which the team at Ginkgo have enormous flair. In an interview months before receiving their government grant, Canton was pretty confident that their skills would be in demand.

“It’s definitely going to be a big business. There’s a big market for writing the short pieces of DNA, and there’s a growing market for products like flavour molecules, and what have you. And there needs to be a bunch of people who are good at putting together the longer pieces of DNA and making sure that they’re the right pieces of DNA.

“That’s where our niche is going to be. It’s pretty valuable.”

If you imagine DNA as text, it boils down to a simple sequence of letters. Chemists, says Canton, can write up to 100 letters of DNA pretty easily.

“But if you want to make one of these products that we’re talking about, you probably need about 1,000 to 10,000 letters” he adds. Once you get above a few ‘words’ of DNA to longer ‘sentences’ and beyond, it’s not simply a matter of spending longer at your desk. Putting together larger strands of DNA means creating assembly reactions.

“There are some companies out there that write words, short strands of DNA,” says Canton. “We operate at a level above that, we take paragraphs of text and put it together in ways that make sense.”

And those paragraphs operate as detailed instructions for the E.Coli bacteria do to pretty much whatever they want it to do. Like make petrol, for example.

E.Coli – Friend or Foe ?

Mixing the dark art of genetic modification with one of science’s most-hated bacteria, as Ginkgo and other scientists do, doesn’t bode well for good PR. Escherichia coli is a nasty piece of work, one of the 99.9% of bacteria that household bleach sprays are proud to kill.

Its benign cousins live quietly in the bowels of most warm-blooded mammals, including you and me. However, the few bad eggs among them cause plenty of gastrointestinal havoc, and its transmission to humans is most commonly fecal-oral, which explains its lack of popularity. E.Coli is associated with unwashed vegetables and under-cooked meat, and the results of ingesting it range from the mild but unpleasant (a tummy upset or diarrhoea) to the potentially fatal, such as when a colon ruptures, giving E.Coli an opportunity to infect the lining of the abdomen. Urinary Tract Infections and even neo-natal meningitis are also part of its perfidious repertoire. It is not the nice guy of science.

So why, then, use E.Coli to make flavour molecules and food additives? Surely mixing a pathogen with your ingredients is a recipe for disaster?

Perhaps not. Like any long-fought battle, rule one is ‘know your enemy’, and genetic scientists have developed a deep and meaningful relationship with E.Coli’s various guises over the years.

“E.Coli is a laboratory workhorse,” says Canton. “It has been used for 60 years during all the early work in figuring out what DNA is and how genes and proteins work. It was all done in E. Coli so it’s the organism that everyone understands the best.

Furthermore, says Canton, there’s little chance of cross-contamination.

“The E. Coli that we work with wouldn’t last ten minutes outside the lab. There’s lab strains that have been evolved over 50 or 60 years that are not toxic, can’t survive in the real world and everyone understands how to use them, how to work with them, and it’s been fully sequenced, its genome. We understand it really well.”

In a turn of redemption akin to DarthVader’s deathbed recant, scientists like Canton have seen the good in organisms like E.Coli and are making it a hero. Using E.Coli to make drugs, for example, can result in a cheap but effective treatments for massively damaging diseases.

“There’s pretty nice stories, like an anti-malarial drug called artemisinin,” says Canton.

Artemesinin comes from a tree native to China, the Annual Wormwood, and the natural process to extract it requires a purification process that is horribly expensive.

“There was initially an academic effort and now a company in California where they figured out how to make the precursor to that drug, first in E. Coli then in yeast.  Now they’re making big vats of yeast to make something that’s almost this drug and that’s much, much cheaper, and you don’t need to deal with purifying this random molecule out of a tree.”

In time, bacteria should be developed that can locate, identify and kill cancer cells, meaning a biological vaccine for cancer.

“In 50 or 100 years, we’re going to be able to do that sort of stuff, engineer bacteria to safely go in and treat problems that right now we treat by horribly crude means like scalpels and chemotherapy. We’ll have these really elegant solutions.”

Squeaky Wheels Get The Grease

The disease on which Ginkgo are  training their bacteria at the moment is America’s addiction to gasoline. The symptoms of that affliction are well-known. Global warming, geopolitical instability and, famously, a slick the size of Florida, off the coast of Florida, heading for Florida. Deep drilling for oil is likely to become more and more common as oil becomes harder to find, and finding a way of producing fuel cleanly and safely will become a licence to print money. Add to that the fact that the fuel will absorb as much CO2 as it release, and you have the enviromentalists on side.

Making the E.Coli seems like the easy part, but in fact Canton and the team at Ginkgoo have high-end collaborators across the US helping them work out the fine details. Jay Keasling, a biofuels expert, advises them from Berkely. David Baker (“a protein design guy”) and Mary Lindstrom (a carbon metabolism expert) have all contributed to getting this project off the Agar plate and into a reactor.

“You’ll have a bioreactor, which looks like something you’d have in a brewery,” says Canton.

“There’s a bunch of E.Coli in there, growing, and you’re bubbling a concentrated source of CO2 through them.  You have a separate plant where you’re making hydrogen through electolysis, and you’re bubbling hydrogen through your bioreactor as well.

“It’s basically like a pot on a stove with gas bubbling through it, and the E.Coli are producing isooctane which is secreted and ends up in the media and floats to the top. Then it can be pulled off and purified a little further and plugged into the liquid fuel stream.”

Batteries Not Included

An underpinning assumption in this project is that the energy to produce the hydrogen, the product’s other input, would come from excess wind power or other renewable sources.

“This is a forward-looking project, the idea being that in 10 years or so there’s going to be cheap and plentiful sources of electricity.”

Wind power will form a major part of that, but wind is notoriously unpredictable. You may have masses of wind at times when no-one wants electricity, meaning the blades are turning but there’s nowhere for the power to go. Conversely, there can be no wind at times when you need energy most. The same thing goes for solar and tidal energy.

Either way, says Canton, “You still have the storage problem with electricity. Battery technology sucks, it’s hard to transport, et cetera. So what they want to do is figure out a way to go from plentiful electricity to liquid fuels that are compatible with existing infrastructure.”

So,why not just use the energy to create hydrogen and convert the national automobile fleet to hydrogen? Well that’s a matter of simple economics. If you can devise a clean fuel that will work with the existing infrastructure, there’s no need for expensive fleet overhauls. Converting millions of private vehicles to hydrogen is just too damn expensive.

The Vice-president and the Department of Energy agreed. The numbers stacked up. Of the $106 million disbursed in May, the $6 million cheque written for Ginkgoo’s project was the biggest of the lot. Until they can create a bacteria that poops dollar bills, this is as big an endorsement as any bio-boffin’s likely wipe up.

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