January 10, 2003

Scientists in Japan have genetically modified silkworms to secrete the human protein collagen. In their cocoons, the insects produced both silk and collagen, which is used to generate artificial skin and cartilage and in cosmetic surgery to fill out lips and wrinkles. The technology has potential to optimize the bulk production of collagen for medical uses.

Female silkworm moth depositing eggs. Courtesy Department of Entomology, University of Nebraska-Lincoln.

This is the first time insects have been used to produce a medically important protein, says Florian Wurm, a biotechnology professor at the Swiss Federal Institute of Technology in Lausanne, Switzerland. Wurm wrote a commentary accompanying the study in Nature Biotechnology.

Currently, most medical collagen comes from cow tissue, which can cause allergic reactions in some patients. Limited quantities of collagen—and other human proteins—are grown in animal cells.

Normal and transgenic adult silkworms (bottom) with red silk glands. ©Nature Biotechnology

Japan Science and Technology Corporation in Hiroshima led the project. Seeking an abundant source of patient-friendly collagen, the researchers turned to an industrious insect. They inserted a human gene for collagen into silkworms. The protein was produced in the silk glands and secreted into cocoons, where the collagen was extracted.

"The production is extremely fast and it appears that the [extraction] technology is not complicated," says Wurm.

Silkworm production is a major industry in India, Japan, China and Europe, and these resources could be converted to manufacture collagen and other human proteins, the researchers say. They estimate that a facility with 1.5 million silkworms could produce 5 kilograms of collagen per year, in addition to silk.

The technology is extremely "low-tech" in the sense that you don't need a molecular biologist to handle the day-to-day manufacturing, says Wurm.

Silkworm cocoons with one cut open to view pupa. Courtesy Department of Entomology, University of Nebraska-Lincoln.

Silkworms are larvae of the caterpillar, Bombyx mori, which has been bred for thousands of years for its production of precious fibers. The species is completely domesticated—no wild populations exist. After hatching from eggs, the worms snack on leaves from Mulberry trees and spin their silky cocoons in about three days.

Backers of the new biotechnology must still overcome some hurdles. Further research is necessary to determine whether insect cells produce the protein differently from human cells, and the collagen would need to be tested in clinical trials.

See related GNN article
»Building a better silkworm with piggyBac

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Tomita, M. et al. Transgenic silkworms produce recombinant human type III procollagen in cocoons. Nat Biotechnol 21 ,52-56 (January 2003).

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