Summer 2003

Nature's Science

Spider silk is one of the toughest known fibers.

By Kaidian Smith

 

spiderweb
photos curtesy of Nexia Biotechnologies

Spiderman has nothing on this new development

 

It all started with the West African dwarf goats and the two common spiders, the garden spider and the golden orb weaver, native to many tropical forests. They might never be as famous as Dolly the sheep, cloned by Ian Wilmut of the Roslin Institute in Scotland. However, Jeffery Turner, molecular biologist and the president of Nexia Biotechnologies, Inc, is betting his career and a great deal of money that these animals could prove to be far more lucrative in the end.

 

Goatphoto curtesy of Nexia Biotechnologies

This goats milk is as smooth as silk.

Spider silk applications

BioSteel, a Nexia development segment, is a recombinant form of dragline spider silk protein synthesized in the milk of transgenic goats. The spiders silk lightweight fiber is strong, elastic, and tough. Its tensile strength is one of its most important attributes because the fiber can withstand great pressure before breaking-perfect for all sorts of economic applications, from military to industrial.

And that is exactly what BioSteel products does. Nexia have prioritized BioSteel- Medicine to lead BioSteel-Industrial because medical applications have higher margins than most industrial applications. BioSteel may be uniquely suited to the medical device market.

Nexia's Biopharmaceuticals patented technology produces recombinant human proteins for the treatment of life-threatening diseases. The large-scale production of authentic, complex drugs is the hallmark of their transgenic animal system. Nexia has focused on a drug, which is used to dissolve clots that may cause both heart attacks and strokes. This type of drug is known as a "clot buster", or a thrombolytic. They are currently researching a new biopharmaceutical product to boost its pipeline, designated NEX-91, for military and civilian market use. For 2003, Nexia intends to get funding for the program and achieve a critical technical milestone.

According to Nexia Biotechnologies Inc. Annual Report 2002, they have identified microsutures, surgical meshes, and artificial ligaments as three attractive BioSteel-Medicine market opportunities. Their initial market opportunities range from $150 to $450 million annually.

Sutures are one of the most common methods of closing wounds and medical professionals continue to search for sutures with improved properties for various applications. The wound closure market is estimated at $15 billion and includes sutures, staples and other wound closure materials. The market is divided equally between the two main types of sutures which are non absorbable and absorbable.

The market for artificial ligaments presents a tremendous opportunity for Nexia because there are currently no such products in the United States market. Artificial Anterior Cruciate ligaments are estimated to be approximately $450 million. Nexia believes that BioSteel- M may be a suitable fiber to develop an artificial ligament, such as an ACL, and they will work to expand initial prototypes in 2004.

Nexia believes that the expected properties of BioSteel- M will make it an ideal candidate to fill the unmet needs in the surgical mesh market. In 1997, there were 700, 000 medical procedures performed to correct hernias in the United States. In most cases, surgical meshes were used to correct the problem resulting in a $300 million market for surgical meshes in the U.S. They anticipate that BioSteel-M surgical meshes could enter the market as soon as 2005.

BioSteel also provides superior antiballistic fabrics combined with high toughness, modulus, strength, and flexibility in light weight material for military and law enforcement applications. BioSteel-I require a commercial spinning process that has consistent specifications for various applications such as technical sporting gear for its further development. To achieve this they have collaborated with Acordis Specialty Fibres to build up a spinning process.

Nexia also thinks their BioSteel- M production levels will be sufficient for development and initial sales that may not be case with BioSteel- I because a larger amount is required. Over the next year, Nexia will continue to expand their herds at both their production facilities and seek out progress partners for high value BioSteel- I applications.

Leaders and their research

Biomimetics, the field that mimics the materials made by living things, have been a resource for spider silk mass-production. According to the Scientific American 50, over the years, Anthoula Lazaris, senior scientist, and Costas Karatzas, senior vice president for R&D, a husband and wife team, and their colleagues at Nexia Biotechnologies in Montreal have achieved the same goal sought after by other companies such as DuPont.

Their spider dragline silk is lighter, much tougher, and more flexible than an equivalent volume of DuPont's Kevlar aramid fiber --the strongest synthetic fiber on the market. Nexia's scientists think the silk should be able to make a lightweight armor that can stop a bullet without weighing down a soldier. In 1990, they identified the two spiders genes that makes the dragline silk protein, but it was the military researchers who first spliced them into bacteria to try to manufacture the material. The bacteria turned out truncated proteins that lacked toughness, so with the companies expertise in areas of mammalian genetic engineering and large-molecule biosynthesis, Nexia decided to tackle the problem.

According to the Scientific American 50, Lazaris and Karatzas were at the technical heart of the effort and everything that Nexia does. With doctorates in molecular biology, Lazaris has a firm grasp on gene expression and Karatzas has a strong background in using that to make large proteins. Lazaris and Karatzas used their combined skills to prove that they could get silk from mammalian cells, splicing the spider genes into cow and hamster cells and culturing them until they could draw off enough protein to work with. Then collaborators at the U.S. Army Soldier and Biological Chemical Command in Natick, Massachusetts used syringes to squeeze out fiber a bit finer than human hair. The fiber turned out more elastic but wider and not quiet as strong as natural dragline silk.

Next, Nexia's scientists spliced the genes into mammary cells in Nexia's untested, fast growing, early lactating breed of goats. Goat mammary glands standing in for a spider's spinnerets can manufacture the silk along with the milk and secrete tiny silk strands from the animal's body by the bucketful. The polymer strands would have to be extracted from the milk and woven into thread. Previously, a few silk-secreting goats have been born, and the company breeds them with hundreds of standard animals on two farms in Canada and the U.S.

A common garden spider's silk producing genes are extracted and tested in the Charlotte machine to determine whether or not the gene will work when it's inside an actual goat. The gene is popped into a goat egg and becomes active only in the mammary glands of adult females. The silk-milk mixture lactation is reduced to "spin dope," then pushed out as silk through a tiny aperture, which mimics the workings of a spider anatomy. When the silk is ready to be stretched and wound, it will be five times as strong as steel. Scientists hope to use it to make, among other things, bullet-resistant clothing.

What's next for Nexia?


 

NATURE'S HELPERS

Nexia, founded in 1993, presently has 100 employees at its three locations: its headquarters in Vaudreuil-Dorion near Montreal, its BioSteel - M/Biopharmaceutical production farm in St. Telesphore, Quebec, and its industrial-grade BioSteel - I production farm in Plattsburgh, New York.

In December 2000, Nexia raised CND $42 million in Canada's largest life sciences initial public offering.

SILK OF STEEL

Spider silk is a lightweight fibre that is strong, elastic, and tough. One of the most important attributes of any fibre is its tensile strength, which measures the load the fibre can withstand before breaking. Elongation is the percentage increase a fibre can stretch relative to its initial length before breaking. Toughness is the amount of energy absorbed by the fibre before it breaks and it's a function to both strength and elongation (shared area). Toughness is a quality important to a rock climber, for example, because the rope must absorb kinetic energy during a fall without breaking, but have enough elasticity to slow the fall. Given this definition, a rope that is elastic and strong will absorb more energy than a rope that is inelastic and strong.

Spider silk is one of the toughest known fibres. One of the unique attributes of dragline spider silk is its biphasic modulus. Essentially spider silk can be thought of as having two different sets of properties. First, spider silk is "stiff" in that it can withstand a load initially without much elongation: the steeper slope of the stress-strain curve. Second, near peak load spider silk becomes more elastic -stretching almost 40% before breaking: the more horizontal slope of the stress-strain curve.

Spider silk has the advantage of having both high strength and elastic properties. From the stress-strain curve, the aramids are extremely strong (they can hold a large load before failure) but are not elastic which means that they break without much elongation. Alternately, nylon is elastic but withstands much less stress.

Spider silk is made from biodegradable protein. Spider webs degrade over time, and it is expected that BioSteel will also have this property. The rate of degradation may be controlled by changing the BioSteel protein used to make the fibre or by coating it.

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