The Pursuit and Development of Spider Silk

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Historically, the idea of a fabric made from spider silk that is strong enough to withstand extreme forces such as being hit by bullets, but soft and comfortable enough to be worn as normal, everyday clothes has been a dream for centuries, but few have been able to produce it until very recently.

In the early 1700’s, the first recorded use of spider silk was by Francois-Xavier Bon de Saint Hilaire, a Frenchman who was successfully able to harvest enough silk directly from spiders to produce gloves, socks, and even a full suit for his king, Louis XIV. It was said that he would go out and gather hundreds of spiders at a time and store them in crates only to return and find only a few left due to the fact that spiders have a tendency to eat each other when placed in close proximity.

A little over one hundred years later, a Spaniard working in Italy named Raimondo de Termeyer was able to produce a pair of stockings and a shawl for Emperor Napoleon and his then wife Empress Josephine. He was able to do this by using a machine that he invented that would immobilize the spider and remove the silk without harming the spider.

In the late 1800’s, a French Jesuit missionary named Jacob Paul Camboué who lived in Madagascar began experimenting with extracting silk from spiders. He later teamed up with another Frenchman who went by Mr. Nogué and, inspired by Termeyer’s design, created a hand powered machine capable of extracting silk from up to 24 spiders simultaneously and combining it into one continuous strand. Using this machine, the team was able to create a set of bed hangings which was on display at the 1900 Exposition Universelle in Paris.

More recently in 2004, using the design documented by Camboué and Nogué, Simon Peers and Nicholas Godley attempted to recreate the machine and create their own spider silk fabric. Every morning they collected new spiders, “milked” them for their silk, and returned them to the wild when they were done with them. The entire process was extremely slow and the amount of silk that could be acquired from each spider was very minimal because it takes around 23,000 spiders to produce only one gram of silk. So, over the course of five years, using over one million spiders, and spending half a million dollars, they had finally produced enough silk to weave a single golden cape decorated with intricately embroidered and appliquéd motifs that depict the spiders that were used to generate the material. This cape is said to be incredibly strong, yet as soft as cashmere.

Milking spiders for their silk can also be used for purposes other than textiles. An old wound remedy that was used as far back as the Roman Empire included gathering spider silk and applying directly to a wound to help the healing process. Borrowing from this, the Department of Plastic, Hand, and Reconstructive Surgery in the Medical School Hannover in Germany has developed a way to utilize a woven mesh of the dragline silk extracted directly from Nephila spp spiders to create an “artificial skin” that may be applied to the skin to repair it without any immune system response. They did this by placing normal skin cells onto a spider silk mesh and, in the right conditions, were able to create the outer and inner layer of skins in only a week’s time. This could be used as a natural alternative to plastic surgery to regrow skin on burn and trauma patients.

Unfortunately, due to the large number of spiders that is required to produce just a small amount of silk and spiders’ cannibalistic nature, it is impractical to harvest silk directly from them. Knowing this, there have been and are currently many companies and organizations trying to get around this by racing to develop and commercialize fibers that have properties similar to that of natural spider silk.

In 1993, a company called Nexia Biotechnologies Inc. was founded in Montreal, Canada by Dr. Jeffrey Turner and Paul Ballard. Originally working and failing to produce lactose-free milk, it found new direction when Dr. Jeff Turner suggested that they work to incorporate spider DNA into the milk to produce spider silk proteins. By licensing research done by one of the world’s top researchers on spider silk, Dr. Randy Lewis, they isolated and cloned the proteins for spider silk and were finally able to produce 10 grams of spider silk proteins in goat milk in 2002. At full capacity, they were producing small quantities of the proteins with each batch of milk harvested and spinning some of them into a fiber that they named “Biosteel™”. Unfortunately, with the extremely limited amount of proteins that could be created in addition to the high cost to produce these proteins, they found that the business was unsustainable. They ended up selling most of their assets in 2005 and finally went bankrupt in 2009.

Dr. Randy Lewis was not giving up and was determined to take this idea further. He took the idea of the “spider goats” and ran with it in parallel with Nexia Biotechnologies, creating his own breeds while working out of the University of Wyoming. He was also in talks with Dr. Don Jarvis, a noted molecular biology professor that specialized in silkworms at the University of Wyoming, to somehow incorporate the spider DNA into the silkworms in a similar manner as the goats.

Meanwhile, Kim Thompson, a business lawyer with a strong interest in the process of making artificial spider silk, had contacted the University of Notre Dame’s Dr. Malcolm Fraser. Dr. Fraser was one of the initial scientists that had worked on producing the first transgenic silkworms as well as one of the researchers who was able to develop a method to replace the DNA in a specific part of an insect with another unique sequence. He called this method “piggyBac”. Thompson was highly interested in using this method to replace the DNA in the silkworm’s spinnerets with spider DNA. Together, Thompson and Fraser contacted Lewis and Jarvis and decided to work together to create this artificial spider silk.

In 2006, Thompson founded Kraig Biocraft Laboratories Inc. and began working to create transgenic silkworms that have been injected with spider DNA. In 2010, they finally achieved their goal and created a silkworm capable of spinning a much stronger silk, which the company dubbed “Monster Silk®”. They published their methods and findings in a PNAS paper and begun ramping up the production of silkworms to commercial quantities. Since then they have also licensed another method for more precise gene insertion called “Zinc finger” from Sigma-Aldrich. Using this method, they were able to produce an even stronger fiber which they dubbed “Big Red”. Recently, they have been working with Warwick Mills, a technical textile company based in New Hampshire, to test and develop their fibers into practical applications. They are also in talks with the Vietnamese government to build a commercial factory pending Vietnamese legislation. They have stated that they hope to be at commercial production levels of Monster Silk® as early as this year.

Dr. Randy Lewis has since moved on with his work, attempting to further develop the production of artificial spider silk. Bringing his “spider goats” with him, he transferred to Utah State University and started diversifying his work, injecting spider DNA into many organisms such as alfalfa plants, E. coli bacteria, and silkworms using even more recently developed methods for replacing DNA such as the CRISPR/Cas9 system. In 2012, he founded his own company, Araknitek Inc., and is determined to bring his own version of artificial spider silks to the market.

Other companies have seen the opportunity that these fibers can provide and have started development using their own methods.

In England, Oxford University’s silk research group lead by Professor Fritz Vollrath with Dr. David Knight founded a company named Spindox Ltd. Rather than inject spider DNA into silkworms, they had developed a method to spin silkworm silk proteins into a stronger silk fiber that resembled the properties of natural spider silk by cleaning and modifying the fibers. They named this fiber “Spidrex®”, changed their name to Oxford Biomaterials Ltd., and are currently working on producing vascular grafts that are more reliable than those on the market today. They have also produced three spinoff companies using and developing Spidrex® fibers: Suturox Ltd., Neurotex Ltd., and Orthox Ltd.

Suturox was founded in 2007 and hoped to develop naturally biodegradable sutures made form Spidrex®, but were unable to do so and were dissolved in 2013. Neurotex, founded in 2006, hopes to commercialize a Spidrex® nerve conduit and is currently working to prefect it. Orthox, founded in 2008, uses Spidrex® fibers to develop a cartilage replacement that they dubbed “FibroFix™”.

A German startup company called Spin’tec Engineering GmbH. Founded by Dr. Michael Rheinnecker in 2004, purchased the spinning technology from Oxford Biomaterials Inc. and has since improved upon it. They are currently working with their own breeds of silkworms and have been embedding biological agents into the silks from the silkworms while still spinning them in such a way that will produce a thread with properties approaching a spider’s thread. They hope to use these threads to assist with bone healing, wound healing, and developing artificial tissues and organs as well as other medical and pharmaceutical uses. They are currently working with the KLS Martin Group to develop an innovative maxillofacial product.

Another German company has been developing an artificial spider silk using a different method. AMSilk GmbH is using E. coli bacteria that have been genetically modified with spider DNA to produce spider silk proteins. They have already successfully commercialized creams and powders for cosmetic use that they named “TruSilk©” and are currently working on making a coating for breast and other silicone implants which they call “Bioshield-S1©” to reduce the possibility of the body rejecting the implant. They also are close to commercializing an over the counter wound care patch that they call “SanaSilk®” that will keep the wound clean and hydrated. They have even been successful spinning fibers from the proteins. They named these fibers “Biosteel®” after Nexia Biotechnologies abandoned the trademark. They are currently working to optimize these fibers and bring them to market.

AMSilk is not the only company using modified bacteria to produce its silk. Spiber Technologies AB was founded in 2008 in Sweden based on the research from the veterinary faculty at the Swedish University of Agricultural Sciences. The founding researchers discovered a method to produce artificial spider silk in physiological conditions and have since developed a recombinant spider silk protein that they call “Spiber™”. These proteins are very versatile as they can be spun into a fiber, made into a thin film, frothed into foam, or cut into a mesh for custom uses. Spiber™ can also be bioactivated with additional functions to better suit final applications. The company is currently working on perfecting the use of their Spiber™ proteins for wound healing, implants, and other medical applications.

Another company with almost the same name, Spiber Inc., was founded in Japan in 2007. The choice for their name was coincidentally the same as the Swedish company and they also use modified bacteria to make their silk proteins, but they are not working together. Since their formation, they have started working with Kojima Industries Corporation and the Korea Advanced Institute of Science and Technology (KAIST) and have been able to build a small pilot facility capable of producing 100Kg of silk protein a month. They have spun some of this protein into a fiber that they have called “QMONOS®” (pronounced “kumo no su” meaning “spider web” in Japanese) and have woven a dress from it. They have recently started constructing an even larger facility capable of producing 20 metric tons of silk protein a year at full capacity and created a spinoff company called Xpiber, Inc. They plan on selling the proteins and fibers for practical applications by the year 2017.

An American company founded in 2007 in North Carolina by Dr. David Brigham named EntoGenetics Inc. is also attempting to create their own transgenic silkworms. It is Brigham’s goal to produce 100% spider silk from a silkworm and produce everything to make the silk in the USA. Initially working out of his home and recently growing mulberry on marginal land at a repurposed water treatment plant, he has created a very strong silk and has a contract with the Army to produce bulletproof vests. He is currently in the process of expanding operations.

Even another American company founded in 2009 in California by UCSF graduate Dr. Dan Widmaier and his partner, UC Berkeley graduate Dr. David Breslauer, goes by the name of Bolt Threads Inc. They have recently changed their name from Refactored Materials Inc. and are also attempting to produce an artificial spider silk. Their initial experiments were working with using transgenic salmonella to generate the silk proteins and have since moved on to other methods. Since their founding, they have been granted over $1 million by the National Science Foundation and a contract with the Department of Defense to produce bulletproof vests. They hope to start selling their silk commercially by 2016.

The Okamoto Corporation, a Japanese luxury sock company, announced in 2007 that they are working on a new sock made from spider silk as generated from genetically altered silkworms. They are currently working with Shinshu University’s Faculty of Textile Science and Technology to commercialize these socks and have already produced a prototype pair of socks. They are currently working on creating a silkworm research and breeding center that should be up and running by spring this year.

Like Nexia Biotechnologies, some other, better established companies that have also jumped on the artificial spider silk bandwagon haven’t done so well In 2001, DuPont, the producer of Kevlar, had experimented with injecting spider DNA into plants, silkworms, and E. coli bacteria to produce fibers with the strength of spider silk, but gave up on the project after only a few years because they could not achieve the mechanical properties that they wanted in a consistent manner.

Artificial spider silk is of great interest and is currently being researched at many universities. Practically every company listed was spun out of a university and there are many more in the process of developing spider silk that may form a company and attempt to commercialize in the future. For example, the National Institute of Agrobiological Sciences (NIAS) in Japan has produced their own transgenic silkworm and has recently used its silk to knit a sweater and scarf and documented everything in a PLOS One article. They have even recently visited the Indian Andhra Pradesh State Sericulture Research and Development Institute (APSSRDI) and looked at their transgenic silkworm programs. They are now looking into expanding production there.

The Wyss Institute for Biologically Inspired Engineering has created genetically modified shrimp injected with spider DNA to harvest their cartilage that they named “Shrilk” in order to create an environmentally friendly, biodegradable plastic.

The Southwest University in Chongqing, China, Tufts University in Medford, MA, USA, the University of the Pacific in Stockton, CA, USA, and likely many others have all been working separately on creating their own version of spider silk.

Modifying organisms with spider DNA has become so common that a team of students from the University of Bordeaux in France even decided to modify E. coli bacteria with spider DNA themselves for entry into the 2014 International Genetically Engineered Machine (iGEM) competition in which they won a bronze medal. They have named this bacteria “Elasicoli” due to its elastic nature, and presented it as a viable green alternative producing to plastics, alternative to medical sutures and replacement tendons, and method to create stronger textiles.

Even with so many companies and organizations simultaneously racing to produce these products, there will still be plenty of room for other competitors to flourish in the market as these fibers start to overtake and replace the current leaders in the industry. It is only a matter of time before we will start seeing these spider silk products available in stores and hospitals worldwide.

Sources:

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4. Wendt H, Hillmer A, Reimers K, Kuhbier JW, Schäfer-Nolte F, et al. (2011) Artificial Skin – Culturing of Different Skin Cell Lines for Generating an Artificial Skin Substitute on Cross-Weaved Spider Silk Fibres. PLoS ONE 6(7): e21833. doi:10.1371/journal.pone.0021833
5. “Nexia Biotechnologies.” McGill Unversity. 30 Oct. 2002. Web. 5 Nov. 2014.
6. Pelzer, Jeremy. “University of Wyoming Professor Helps Create ‘monster’ Silk.” Casper Star-Tribune Online. 1 Feb. 2012. Web. 5 Nov. 2014.
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9. “A Method of Spinning Spider-like Silk, the ‘Holy Grail’ of Bio Materials.” Oxford University. Inside: Technology, Issue 8, The Technology Partnership Plc., 20 July 2012. Web. 5 Nov. 2014.
10. Kuwana Y, Sezutsu H, Nakajima K-I, Tamada Y, Kojima K (2014) High-Toughness Silk Produced by a Transgenic Silkworm Expressing Spider (Araneus ventricosus) Dragline Silk Protein. PLoS ONE 9(8): e105325. doi:10.1371/journal.pone.0105325
11. “Team:Bordeaux.” Web. 5 Nov. 2014. < http://2014.igem.org/Team:Bordeaux >
12. Fujisaki, Masahiko. “Project under Way in Kyoto to Commercialize Spider-silkworm Thread – AJW by The Asahi Shimbun.” AJW by The Asahi Shimbun RSS. N.p., 27 Nov. 2014. Web. 03 Dec. 2014.

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Source by Ryan Chapman