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THE SILK GENE
Sericulture may be on its way out. In the past decade, scientists have come up with several ways of producing silk cheaply, in bulk, without spiders or silkworms, all by utilizing the power of genomics. Progress started in 1999 when a geneticist named Randolph Lewis at the University of Wyoming decoded the silk gene sequence of Nephila clavipes spiders (“orb weavers”), identifying the genetic instructions that those spiders follow to assemble silk protein. Since the genes of all living things are conveniently written in the same programming language, that of DNA, a fully functional snippet of DNA identical to the orb weaver’s silk gene can be inserted into the DNA of other life forms. The silk gene, once identified in spiders, could theoretically be used to make any organism create silk.
Soon after Lewis decoded the silk gene, molecular biologists at a Canadian company called Nexia Biotechnologies inserted it near the milk gene in goat egg cells. These were fertilized, gestated, and born, growing up to be world-famous goats that in 2002 produced a syrupy solution of silk in their milk. The tricky part, according to the biologists, was gleaning silk protein from the syrup and turning it into a product they called BioSteel—the first “transgenic” material ever made. Despite the company’s processing difficulties, the New York Times Magazine described Nexia’s research as writing “a new chapter in biotechnology.”
There were still more chapters to come on the subject of neat-and-tidier ways to make silk. A group led by Sang Yup Lee at KAIST, a technology institute in Korea, chose to slip the silk gene into the DNA of Escherichia coli bacteria. E. coli is the darling of molecular biology, due to its simple genome and low-maintenance laboratory growth. It also is unusually proficient at following genetic orders. By transplanting spider DNA into E. coli, the KAIST biologists created strains of the bacteria that synthesize silk protein in less than a day. Two more days of purification produce a solution of liquefied silk, and so, after a mere three days’ work, the technique produces silk, in a process far more efficient than that used by traditional silk farmers. Lee and his colleagues believe their method of transgenic silk cultivation is ready to be scaled up and commercialized.
Alternatively, several other groups of biologists, most notably a team led by Udo Conrad and Jurgen Scheller in Germany, are growing silk protein in transgenic tobacco and potato plants. In a recent article the scientists noted that plant organs like seeds and tubers serve as ideal storage containers for transgenic proteins; they also argue that their method is better-suited for commercialization than KAIST’s bacterial method, since “mass production of plants is common … and harvesting technologies are well-developed.”
Back at Tufts, Kaplan (who follows all transgenic silk developments closely) agrees that the crop farming method may ultimately be the most sustainable since plant growth is powered by the Sun; some bacteria rely on messier methods of obtaining energy. He also finds it aesthetically appealing. “I picture a world of small family ‘pharms’,” he said, “growing, alongside food, a huge range of pharmaceuticals, as well as incredibly useful materials like collagen and silk.”
A healthy competition between the animal, bacterial, and vegetal camps is playing out in the world’s top-tier journals. In the end, though, whether silk is grown in fields of transgenic tobacco, tubs of E. coli, or goat’s udders, it seems clear that silkworms’ and spiders’ monopoly is over.
A NEW ROAD FOR SILK
The textile industry may well benefit from efforts to produce silk in bulk, but scientists are not interested in cheapening its manufacture merely for the sake of fashion. In the hands of the Tufts scientists and their collaborators, the uses of silk seem virtually endless, and revolutionary. Juan Enriquez, who Fortune has also profiled as “Mr. Gene”, is a venture capitalist and the founding director of the Life Sciences Project at Harvard Business School. Enriquez is a leading authority on the economic impacts of biotechnology, and has lately become enthralled by Kaplan’s and Omenetto’s research.
“What’s exciting about the project is that there are so many broad applications for it,” he remarked. “Silk has led to the rise and fall of civilizations, and now here are two interesting, quirky, smart scientists leading the re-engineering of this familiar material, in a huge range of ways that nobody’s thought of. It’s so broad,” he added. “They are such broad thinkers.”
Concerning silk, their thoughts were largely without precedent. Despite the thousands of years during which people marveled at the material’s miraculous strength and luster, almost nothing was known of its true nature when Kaplan entered the silk scene as a graduate student in the 1980s. He verified that silk is a protein, then spent a decade studying its chemical and mechanical properties. He was doing the sort of research that scientists often find hard to justify to taxpayers: work driven by curiosity, which doesn’t promise immediate benefit. “There was not even a hint of thinking about applications at that point,” Kaplan recently recalled. “I was just fascinated by the fundamentals.”
He was grasping the scientific explanations of silk’s well-known traits; determining, for example, that its strength arises from hard-to-break hydrogen bonds that form between adjacent protein chains. As his research progressed, completely new, unexpected traits began revealing themselves as well, offering Kaplan tantalizing glimpses of the material’s true potential. Silk was turning out to be even more incredible than he, or anyone, knew.
Depending on how it is processed, silk can take on a variety of manifestations. It can be a fiber, a liquid, a sponge, or a gel; it can be poured into a mold and hardened as a solid plastic. In all these forms it is optically transparent. This is hard to tell from silk fabric, which has tightly-woven fibers that tend to scatter light, but silk itself is clear, as anyone who has ever walked through an unseen spider web can confirm.
Best of all, silk is extremely biocompatible: It meshes well with living things, whether beneath or on top of their skin. Nobody knows quite why this is so, but Kaplan has offered the most likely hypothesis. “The protein is made of amino acids like glycine and alanine which are extremely hydrophobic (water-repellant),” he explained, “so when you implant silk inside the body, which is a very watery place, we think it’s as if your body doesn’t see it.” Silk isn’t entirely ignored by the body’s immune system. Inside the body, rather than being attacked by an army of white blood cells, silk is gradually broken down, and its amino acids are recycled and used.
In short, silk is a malleable, clear, organic, phase-changing, biotic material, the like of which does not exist elsewhere on this planet. As more uses for it are imagined and actualized, what began as purely curiosity-driven science has evolved into a research project that Enriquez has described as possessing “the potential to change the world.”
For instance, a range of novel silk-based technologies is already changing healthcare. Silk tissue scaffolds engineered by the Tufts group several years ago were the first of these technologies to receive FDA approval, under the name SeriScaffolds by a spin-off company called Serica Technologies. Last year Serica was bought by Allergan, a large pharmaceutical manufacturer, and their products have now hit the market. The scaffolds are made of spongy silk that has the look and feel of human tissue. Implanted during reconstructive surgery, they can support or restructure damaged ligaments, tendons, and other tissue; due to their biocompatible nature they simply degrade over time as natural tissue grows over and around them.
A potentially higher-impact development is that of doped silk implants, which aim to revolutionize drug delivery, especially for the treatment of chronic illnesses. According to Eleanor Pritchard, a Tufts engineer, the dime-sized implants are made by blending drugs into a liquid silk solution and then shaping and hardening the mixture to form a small film. The drugs stay evenly mixed throughout the film; on the molecular level, they are locked in a grid of silk proteins. When the film is implanted under the skin, the silk biodegrades, gradually releasing the drug at a steady rate. The time frame over which the silk breaks down, which can range from days to years, is a precisely controllable parameter that depends on what percentage of the silk has crystallized during fabrication. Pritchard explained that this technology is directed toward patients in need of long-term drug supplies. “Instead of taking daily growth-hormone shots, or dosages of anti-seizure medications,” she observed, “patients can get these implants and receive a constant, stable dosage of whatever it is they need.”
One benefit of this method of drug delivery is its ability to circumvent what is called the “blood-brain barrier” —a precautionary feature of physiology that stops many drugs carried by the blood from circulating into the brain. For epilepsy patients who have insufficient levels of a chemical called adenosine in their brains, the blood-brain barrier prevents supplements from reaching the brain via the bloodstream and, according to Pritchard, renders a third of epilepsy cases untreatable. But with the advent of the new technology, a small silk rod doped with adenosine can be inserted directly into the brain—a surprisingly minor surgery—to provide a steady, long-term supply of the chemical supplement as the rod biodegrades. According to the scientists, a single silk rod could prevent epileptic seizures for years. Pritchard noted that this technology has already been tested in rats and could be ready for human patients as soon as next year.
Silk may have the strength to break down another major healthcare barrier as well. Currently, effective delivery of many drugs requires a temperature-controlled supply line, or “cold chain,” leading from the point of a drug’s manufacture to that of its destination. Continuous refrigeration is necessary to prevent antibiotics and vaccines from getting too hot and clumping—an irreversible process which renders them chemically inert. However, vast swaths of the globe lack adequate resources (e.g. electricity and refrigerated trucks) to maintain the cold chain, and consequently, according to the Gates Foundation, an estimated 4 million people die of preventable diseases every year from lack of antibiotics and vaccines.
But drugs are stabilized when mixed into capsules of silk; they are unable to clump, and can stay chemically active for years without needing refrigeration. When the silk-antibiotics capsules arrive at their destination, perhaps in a sweltering village in Niger, they can simply be dissolved and gulped down in a glass of water. Kaplan reported that this drug-storage technology is undergoing the final stages of testing, and that he and his colleagues are “in talks with potential funding partners.”
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