Clean tech enthusiasts rework genetic codes for industrial use

A decade ago, a group of biologists, venture capitalists and computer whizzes in the U.S. gathered under the name “clean tech.” They hoped to overturn polluting industries with microorganisms cheerily recycling industrial chemicals through the miracle of reprogramming nature’s genetic code.

The idea lost billions of dollars. Genes may indeed be programmable code, akin to computer software, but it turned out nature was more complex than first believed.

Now, with less fanfare, a few clean-tech companies are aiming for a comeback. And the big idea has not changed much: Create cheap, safe and natural materials for fuel, cosmetics and other goods, much the way yeast ferments sugars into alcohol.

This time around, they believe they have better tools for editing genetic codes, measuring results and automating how chemicals are produced at a large scale. They have also set their sights lower, for now targeting just a few chemicals, not remaking how the world powers cars.

“This is like agile programming, but for biology,” said Eric Steen, a co-founder of Lygos, a California start-up creating yeasts that make malonic acid, an ingredient in fragrances commonly derived from cyanide. “Evolution is the most powerful algorithm ever, but you have to figure out how to stack it in your favour.”

In computer-based agile programming, small teams reinforce positive signals about the way their code is working online. The Lygos version of this is to rapidly measure the performance of a novel yeast strain and quickly build on those results with gene-editing tools that are 100 times faster than when Mr. Steen was in graduate school, 15 years ago.

Big data

“It’s a big data problem,” he said, echoing one of the trendiest terms in computing. “There’s 2,000 genes in this yeast, and each gene may use 300 amino acids. There’s well over a million variants. Our first successful strain had just a tiny poop of malonic acid as a byproduct, but we seized on that, and kept building on it.”

The company, which Mr. Steen and others spun out of the University of California, Berkeley, in 2011 with a $150,000 grant from the U.S. Energy Department, recently secured $13 million, on top of $8 million it got from the government and a few private investors over the years.

It is natural to look at genetic engineering and think of H.G. Wells’ Dr. Moreau, creating an island of miserable and dangerous freaks. At the same time, altering genes is what mankind has done for millenniums, breeding wolves into Chihuahuas and cobs of loose-podded maize into big, uniform ears of corn.

What is different, and troubling to some, are the tools and the time scale. By directly altering the genetic make-up of plants and animals, the creations happen a thousand or more times as fast.

Lygos and other contemporary bio-based manufacturers benefit in particular from a tool called Crispr, which can snip into a sequence of DNA and insert desired features, like a propensity to create malonic acid. The process underlying Crispr was first observed in bacterial behaviour and then experimentally demonstrated in 2007, too late for the first bio-based chemical companies.

This capability, commonly spoken of as the genetic version of cutting and pasting in a word-processing program, bypasses the slow adjustments to a complex ecosystem that happen when nature brings forth a new species.

Nature’s complexity is one reason clean tech fell short. Amyris, a clean-tech pioneer in Emeryville, California, first worked on anti-malarial drugs with backing from Bill Gates, then set out to make bio-fuels. Amyris found that organisms created in a California lab behaved differently in a Brazilian factory. The company spent $250 million trying to figure out the problem while regular oil prices fell.

“It turned out, we had to track every part of the process and automate as many things as possible,” Peter Denardo, a company spokesman, said. “We’ve hired a lot more software and analytics people.”

At least some big producers agree that these new tools and styles of genetic coding are reviving the clean-tech field.

“We have better tools, better computational biology,” said Markus Pompejus, who runs a biotechnology program for BASF, the German chemical giant. “The whole thing is very real. It’s already getting big.” — New York Times News Service