Companies rush to build ‘bio-factories’ for medicines, flavorings and fuels

For scientist Jack Newman, creating a new life-form has become as simple as this: He types out a DNA sequence on his laptop. Clicks “send.” And a few yards away in the laboratory, robotic arms mix together some compounds to produce the desired cells.

Newman’s biotech company is creating new organisms, most forms of genetically modified yeast, at the dizzying rate of more than 1,500 a day. Some convert sugar into medicines. Others create moisturizers that can be used in cosmetics. And still others make biofuel, a renewable energy source usually made from corn.

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“You can now build a cell the same way you might build an app for your iPhone,” said Newman, chief science officer of Amyris.

Some believe this kind of work marks the beginning of a third industrial revolution — one based on using living systems as “bio-factories” for creating substances that are either too tricky or too expensive to grow in nature or to make with petrochemicals.

The rush to biological means of production promises to revolutionize the chemical industry and transform the economy, but it also raises questions about environmental safety and biosecurity and revives ethical debates about “playing God.” Hundreds of products are in the pipeline.

Laboratory-grown artemisinin, a key anti-malarial drug, went on sale in April with the potential to help stabilize supply issues. A vanilla flavoring that promises to be significantly cheaper than the costly extract made from beans grown in rain forests is scheduled to hit the markets in 2014.

On Wednesday, Amyris announced another milestone — a memorandum of understanding with Brazil’s largest low-cost airline, GOL Linhas Aereas, to begin using a jet fuel produced by yeast starting in 2014.

Proponents characterize bio-factories as examples of “green technology” that are sustainable and immune to fickle weather and disease. Backers say they will reshape how we use land globally, reducing the cultivation of cash crops in places where that practice hurts the environment, break our dependence on pesticides and result in the closure of countless industrial factories that pollute the air and water.

But some environmental groups are skeptical.

They compare the spread of bio-factories to the large-scale burning of coal at the turn of the 20th century — a development with implications for carbon dioxide emissions and global warming that weren’t understood until decades later.

Much of the early hype surrounding this technology was about biofuels — the dream of engineering colonies of yeast that could produce enough fuel to power whole cities. It turned out that the technical hurdles were easier to overcome than the economic ones. Companies haven’t been able to find a way to produce enough of it to make the price affordable, and so far the biofuels have been used only in smaller projects, such as local buses and Amyris’s experiment with GOL’s planes.

But dozens of other products are close to market, including synthetic versions of fragrances extracted from grass, coconut oil and saffron powder, as well as a gas used to make car tires. Other applications are being studied in the laboratory: biosensors that light up when a parasite is detected in water; goats with spider genes that produce super-strength silk in their milk; and synthetic bacteria that decompose trash and break down oil spills and other contaminated waste at a rapid pace.

Revenue from industrial chemicals made through synthetic biology is already as high as $1.5 billion, and it will increase at an annual rate of 15 to 25 percent for the next few years, according to an estimate by Mark Bünger, an analyst for Lux Research, a Boston-based advisory firm that focuses on emerging technologies.

Reengineering yeast

Since it was founded a decade ago, Amyris has become a legend in the field that sits at the intersection of biology and engineering, creating more than 3 million organisms. Unlike traditional genetic engineering, which typically involves swapping a few genes, the scientists are building entire genomes from scratch.

Keeping bar-code-stamped vials in giant refrigerators at minus-80 degrees, the company’s repository in Emeryville, Calif., is one of the world’s largest collections of living organisms that do not exist in nature.

Ten years ago, when Newman was a postdoctoral student at the University of California at Berkeley, the idea of being able to program cells on a computer was fanciful.

Newman was working in a chemical engineering lab run by biotech pioneer Jay Keasling and helping conduct research on how to rewrite the metabolic pathways of microorganisms to produce useful substances.

Their first target was yeast.

The product of millions of years of evolution, the single-celled organism was capable of a miraculous feat: When fed sugar, it produced energy and excreted alcohol and carbon dioxide. Humans have harnessed this power for centuries to make wine, beer, cheese and other products. Could they tinker with some genes in the yeast to create a biological machine capable of producing medicine?

Excited about the idea of trying to apply the technology to a commercial product, Keasling, Newman and two other young post-docs — Keith Kinkead Reiling and Neil Renninger — started Amyris in 2003 and set their sights on artemisinin, an ancient herbal remedy found to be more than 90 percent effective at curing those infected with malaria.

It is harvested from the leaves of the sweet wormwood plant, but the supply of the plant had sometimes fluctuated in the past, causing shortages.

The new company lined up high-profile investors: the Bill & Melinda Gates Foundation, which gave $42.6 million to a nonprofit organization to help finance the research, and Silicon Valley luminaries John Doerr and Vinod Khosla, who as part of a group invested $20 million.

As of this month, Amyris said its partner, pharmaceutical giant Sanofi, has manufactured 35 tons of artemisinin — roughly equivalent to 70 million courses of treatment. The World Health Organization gave its stamp of approval to the drug in May, and the pills are being used widely.

Concerns about risks

The early scientific breakthroughs by the Amyris founders paved the way for dozens of other companies to do similar work. The next major product to be released is likely to be a vanilla flavoring by Evolva, a Swiss company that has laboratories in the San Francisco Bay area.

Cultivated in the remote forests of Madagascar, Mexico and the West Indies, natural vanilla is one of the world’s most revered spices. But companies that depend on the ingredient to flavor their products have long struggled with its scarcity and the volatility of its price.

Its chemically synthesized cousins, which are made from petrochemicals and paper pulp waste and are three to five times cheaper, have 99 percent of the vanilla market but have failed to match the natural version’s complexity.

Now scientists in a lab in Denmark believe they’ve created a type of vanilla flavoring produced by yeast that they say will be more satisfying to the palate and cheaper at the same time.

In Evolva’s case, much of the controversy has focused on whether the flavoring can be considered “natural.” Evolva boasts that it is, because only the substance used to produce the flavoring was genetically modified — not what people actually consume.

“From my point of view it’s fundamentally as natural as beer or bread,” said Evolva chief executive Neil Goldsmith, who is a co-founder of the company. “Neither brewer’s or baker’s yeast is identical to yeast in the wild. I’m comfortable that if beer is natural, then this is natural.”

That justification has caused an uproar among some consumer protection and environmental groups. They say that representing Evolva’s laboratory-grown flavoring as something similar to vanilla extract from an orchid plant is deceptive, and they have mounted a global campaign urging food companies to boycott the “vanilla grown in a petri dish.”

“Any ice-cream company that calls this all-natural vanilla would be committing fraud,” argues Jaydee Hanson, a senior policy analyst at the Center for Food Safety, a nonprofit public interest group based in Washington.

Jim Thomas, a researcher for the ETC Group, said there is a larger issue that applies to all organisms produced by synthetic biology techniques: What if they are accidentally released and evolve to have harmful characteristics?

“There is no regulatory structure or even protocols for assessing the safety of synthetic organisms in the environment,” Thomas said.

Then there’s the potential economic impact. What about the hundreds of thousands of small farmers who produce these crops now?

Artemisinin is farmed by an estimated 100,000 people in Kenya, Tanzania, Vietnam and China and the vanilla plant by 200,000 in Madagascar, Mexico and beyond.

Evolva officials say they believe there will still be a strong market for artisan ingredients like vanilla from real beans and that history has shown that these products typically attract an even higher premium when new products hit the market.

Other biotech executives say they are sympathetic, but that it is the price of progress. Amyris’s Newman says he is confused by environmental groups’ criticism and points to the final chapter of Rachel Carson’s “Silent Spring” — the seminal book that is credited with launching the environmental movement. In it, Carson mentions ways that science can solve the environmental hazards we have endured through years of use of fossil fuels and petrochemicals.

“The question you have to ask yourself is, ‘Is the status quo enough?’ ” Newman said. “We live in a world where things can be improved upon.”

 
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