Spinning Gold From Goats

Canadian Biotech Says It's Found a Way to Mass-Produce Spider Silk

By Terence Chea
Washington Post Staff Writer
Friday, May 31, 2002; Page E01

       Spiders and their intricate webs fascinated humans long before the Hollywood blockbuster "Spider-Man." For centuries, people envied the arachnid's ability to ensnare fast-flying insects with its delicate silk threads. Flexible and lightweight, the best spider silk is five times as strong as steel.

Despite relentless efforts, scientists couldn't figure out how to produce spider silk in large quantities. Unlike silkworms, fiercely territorial spiders can't be farmed because they will eat each other before satisfying demand for their valuable proteins.

Now researchers believe they have found the perfect spider-silk factory where few would look: the udders of dairy goats. On farms in the Montreal suburbs and in Upstate New York, researchers are breeding hundreds of goats genetically engineered to produce milk rich with spider-silk proteins that can be spun into fiber.

Officials at Nexia Biotechnologies Inc., the Canadian company that raises the goats, envision a burgeoning market for its spider-silk fiber, which it calls BioSteel. The military wants comfortable body armor strong enough to protect against bullets. The company also sees medical applications such as artificial ligaments and super-strong thread for surgery. Other products include biodegradeable fishing line and designer clothes.

"Nexia is trying to mimic what the spider does," said Jeffrey Turner, Nexia's president and chief executive. "Man always thinks strong things have to be big, but the spider has basically dwarfed what we've done with petroleum-based materials."

The development of industrial spider silk illustrates how biotechnology is harnessing the genetic machinery of nature to create innovative materials. The biotech revolution was launched in the late 1970s, when researchers figured out how to insert foreign genes into bacteria and produce large quantities of protein-based medicines. In the 1990s, scientists learned how to splice foreign genes into farm animals, transforming them into walking drug factories.

While no other research groups are developing synthetic spider silk in animals (or have publicized such efforts, at least), some researchers are making attempts in plants. Last year, German scientists announced they had successfully produced spider-silk proteins in potatoes. And researchers at the University of Wyoming are trying to splice spider-silk genes in alfalfa plants after accomplishing the task in a mustard plant.

Forged over 400 million years of evolution, spider silk is considered the Holy Grail of performance fibers. Three times as strong as Kevlar -- a petroleum-based material used to make bullet-proof vests -- spider silk is one of the strongest materials on earth that can be woven into a fiber. Researchers estimate the strongest spider silk can withstand up to 600,000 pounds per square inch.

Attempts to domesticate spiders failed miserably. While silkworms are content living in close quarters and munching on mulberry leaves, spiders are cannibalistic predators that resist socialization.

"If you put a whole bunch of spiders together, they're going to eat each other until there's enough space for them to be satisfied territorially," said Randy Lewis, a molecular biologist at the University of Wyoming at Laramie who studies spider-silk genes.

The latest attempt to find a new source of spider silk began in the mid-1960s during the Vietnam War, when military scientists began searching for new materials to protect soldiers on the battlefield. They wanted to develop an alternative to Kevlar, which is heavy, not very flexible, and is made from toxic chemicals.

After years of research, they discovered that a group of spiders called orb weavers make the highest-quality silk. Orb weavers make seven types of silk proteins, which are stored in a spider's glands until the spider is ready to spin thread. Researchers determined that the best silk was "dragline" or "frame" silk, which spiders use to hang from ceilings and weave the spokes of their webs.

Despite this knowledge, there was no way to produce large amounts of spider silk until genetic engineering came along. The breakthrough science allowed researchers to isolate genes that code for valuable proteins such as insulin and insert them into a bacterium such as E. coli. The genetically modified bacteria could then be grown in large fermenters and purified into protein-based medicines.

In 1990, Lewis, with funding from an Army research grant, identified the two genes needed to make dragline spider silk. With that genetic information, scientists at the U.S. Army Soldier and Biological Chemical Command in Natick, Mass., the University of Wyoming and chemical maker DuPont Co. tried to use genetic engineering to produce large amounts of spider-silk protein.

But attempts to coax bacteria into making the proteins had limited success. Researchers were able to produce small quantities of silk proteins, but the silk was of poor quality. Spider silk derives its strength from the repetitive nature of its genes. But the bacteria would cut out units of the gene, resulting in shorter proteins that made for inferior fiber.

"The bacteria did not like making the silk protein," said Steve Arcidiacono, an Army microbiologist who has researched spider silk for nine years. "We could make only small amounts, and the small amounts were typically very brittle -- nowhere near what the spider is capable of doing."

Scientists at DuPont, which began research into synthetic spider silk in the late 1980s, developed an artificial strand of DNA to produce proteins with spider-silk properties, but they had difficulty spinning the proteins in fibers, said John O'Brien, the researcher who headed the project. The company shelved the program two years ago.

Researchers also tried using yeast, a more complicated organism, but the fermentation and purification process damaged the silk protein.

Then along came Nexia Biotechnologies. In 1993, Turner, an animal genetics researcher at McGill University in Montreal, started the company to genetically modify cows to produce lactose-free milk. But that idea fizzled in the mid-1990s when the start-up's partner, a Canadian dairy company called Ault Foods, was acquired, and it pulled out of the project.

Nexia began looking for other high-value proteins to produce in transgenic animals -- animals with foreign genes. At that time, several biotech ventures were launched to create transgenic animals, which potentially offered a more efficient, less expensive way to make protein-based medicines. Nexia's first project was to produce dairy goats that would make a clot-dissolving drug called TPA in their milk.

In 1998, Turner became fascinated by spider silk and the failed attempts to make it. Seeing similarities between the glands of spiders and goats, he believed Nexia's transgenic goat technology could solve the problem.

"Everywhere we looked, people wanted spider silk, but no one could get it. We said, 'Hey, there could be an opportunity here,' " Turner said. "It was an intoxicating molecule because it resisted an enormous amount of experimentation."

The company licensed rights to the technology to isolate and clone spider-silk genes from the University of Wyoming. Then it struck a research partnership with the Army center at Natick, which could spin silk protein into fiber but could not make large quantities of it. In December 2000, the company sold the story to investors, raising $40 million (Canadian) in one of Canada's largest biotech stock offerings.

After three years of research, Nexia scientists made a major breakthrough. They produced high-quality spider-silk protein by inserting spider-silk genes into the cells of cow mammary glands and hamster kidneys. Then military scientists purified the proteins and squeezed them into tiny tubes, where they form super-strong silk threads with a strength approaching that of natural spider silk. In January, when the company published its findings in the journal Science, the Nexia's stock jumped 40 percent.

"It's a big step forward," the Army's Arcidiacono said. "It was the first time anybody had spun recombinant silk fibers that had meaningful properties."

Since then, the company has produced dozens of transgenic goats by inserting the spider-silk genes into goat embryos. The transgenic goats, which look just like ordinary goats, produce the silk protein in their milk and pass on that genetic trait to offspring through traditional mating.

Now the company wants to demonstrate that it can produce spider-silk protein on an industrial scale. The company is breeding the transgenic goats with more than 1,000 ordinary goats on a farm outside Montreal and a 65-acre decommissioned military base in Plattsburgh, N.Y.

Nexia recently announced it has struck a deal with a major medical textile supplier and it's in talks to partner with sporting gear makers. With genes for several kinds of spider silk, the firm hopes to eventually sell a variety of fibers with different properties.

Turner appreciates the interest the movie "Spider-Man" has generated in spiders and spider silk, but he believes Hollywood misrepresented the strength of spider silk. Because spider-silk is so strong, he said, the superhero wouldn't need webs as thick as rope to swing from skyscrapers and capture bad guys. A much thinner thread would do.

2002 The Washington Post Company