Tuesday, June 03, 2008

A gene-altering technology from biotech Sangamo BioSciences may radically change what we eat.

Jerome Peribere, the chief executive of Dow AgroSciences, has a slide show for investors. It explains how one could theoretically turn the offspring of a wild, berry-size tomato into a plant bearing full-size tomatoes just by tinkering with one gene. The sweet corn we eat for dinner would be a shriveled gray precursor called teosinte were it not for the activity of a handful of genes. Food scientists have understood these distinctions for a decade thanks to traditional plant biotechnology research. It's what's on the next few slides that gets Peribere going: the possibility of easing world hunger by turning inedible oil crops like crambe into edible versions; tomatoes that will always taste good; crops that can survive through severe drought. These traits could be edited into a new form of the same species in a far more precise and accurate way than with the existing tricks in genetics' kit bag.
In Pictures: Foods Of The Future

This technology, which Dow AgroSciences is moving toward the market, is called a zinc finger, a naturally occurring protein that can be used in a cell nucleus like an editor's red pencil. Zinc fingers, so named because they contain a zinc atom and are shaped like an index finger, can turn specific genes off or on or to some point in between, delete genes altogether or add new genetic material. "Within biotech," says the 54-year-old Peribere, "we believe this is one of the very disruptive technologies."

Success with the zinc finger could also give Dow AgroSciences, the crops unit of $54 billion (sales) Dow Chemical (nyse: DOW - news - people ), the second-largest chemical company in the world, a bigger share in the global agbiotech boom. Monsanto (nyse: MON - news - people )'s stock is up sevenfold since 2004 (trouncing Dow shares) thanks to its huge success selling seeds bioengineered to fight off bacteria and withstand direct application of Monsanto's own weed killer Roundup. Peribere's group, with $3.8 billion in revenue, lacks a significant presence in the genetically modified seed business. Its sales still come mostly from weed and bug killers, and in sum are less than half the sales of either Monsanto or Syngenta (nyse: SYT - news - people ). But zinc fingers, because of their precision, could give Dow a significant leg up by cutting a year or two off the six to eight years it now takes to develop a modified plant and get it past regulators.

In October 2005 Dow AgroSciences entered into an exclusive research agreement with Sangamo BioSciences (nasdaq: SGMO - news - people ), a biotech company in Richmond, Calif. that controls most of the intellectual property around zinc finger research. It has drugs in development for ten diseases and two ongoing clinical trials, including ones for diabetic nerve injuries. Sangamo has also licensed its technology to Sigma-Aldrich (nasdaq: SIAL - news - people ), a chemicals firm, for use in discovering novel reagents for research. Amgen (nasdaq: AMGN - news - people ) and Genentech (nyse: DNA - news - people ) are also using Sangamo's zinc finger proteins to improve their manufacturing yields.

"We can target and regulate genes inside any cell in any organism," boasts Edward Lanphier, founder and chief executive of Sangamo. "This is enormously powerful science."

Dow Agro will likely sign an exclusive commercial licensing agreement with Sangamo between now and October, paying it royalties on sales of products developed using zinc finger proteins. So far Dow Agro has paid Sangamo $20 million, including a $4 million equity investment. The first fruits of the partnership aren't expected for four more years. Dow is coy about its plans, but Peribere drops hints.

"What about dramatically improving the sugar content in sugarcane?" he asks. Dow Chemical, in a separate project, already plans to make polyethylene from sugarcane ethanol in Brazil. Upping the sugar content in the cane would lead to a higher yield of ethanol per acre. A second possibility: altering specific genes to make it easier to break down the lignin in the cell walls of corn leaves and stalks, with an eye to making so-called cellulosic ethanol out of the unused part of the plants. Dow Agro biologists have already accurately inserted genetic material into specific locations in maize and rapeseed genomes using Sangamo's technology.

Use of highly targeted gene-modification tricks comes at a fortuitous time. Biologists are unearthing a trove of genomic information about plants. The rice genome was fully mapped in 2005. Corn's rough DNA blueprint was released in February, and the soybean's DNA is being mapped now. With maps in place, Dow and Sangamo's zinc fingers can be aimed directly at the genetic locations that would play the biggest role in curtailing the recent and sure to be ongoing disruptions in food and biofuels supply. "We are at the stone age of plant biotechnology," says Peribere. "In 25 years we are going to be laughing about what we are doing now."

Zinc fingers may also offer a way to get some genetically altered foods through regulatory approval faster than before. The European Commission and armies of environmentalists battled Monsanto nearly to a standstill over its GM seeds, but thanks to pressing global grain demand, Monsanto eventually won approval in all the world's biggest markets. The knock against Monsanto's technology was the use of foreign genes, something that Peribere says zinc fingers can avoid. When zinc fingers are used to delete genetic material, the mechanism for doing so, called a zinc finger nuclease, does not remain in the plant for more than a few days. "Our expectation is that as you are not introducing anything that stays in the plant, this is going to be considered non-GMO [by regulators]," Peribere told analysts in December.

That remains to be seen. Greenpeace International, a vocal opponent of genetically modified crops, is skeptical that zinc fingers can evade the GMO labeling. "It's not 100% clear, but I think that most of this would still be considered GMO because you're introducing a new gene, even if [the finger] doesn't stay in the plant," says Greenpeace International scientist Janet Cotter. Friends of the Earth Europe, another anti-GMO group, says that the Sangamo technology may well turn out to be a type of genetic modification that it would oppose.

If, that is, Sangamo crops ever make it out into the field. Zinc fingers are still unproved outside the lab. Dana Carroll, a biochemist at the University of Utah who has licensed some research to Sangamo, has run fruit fly experiments using zinc finger nucleases in which the flies' genomes were cut in unintended places apart from the target area. Sangamo and other researchers have worked to fix some of this errant DNA editing, but Carroll says it is impossible to know if all unintended cutting has been eliminated.

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