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Silk from Milk

The gossamer, flexible, yet incredibly durable material that spiders spin out in order to catch oblivious flies and other hapless insects is one of the finest marvels of nature that has often served as both a representation of finesse and a symbol of dread in many writings. Spider-less silk is also one of the nature’s most sought-after materials. And, now researchers from Nexia Biotechnologies in Montreal seem to be on the verge of manufacturing it in large quantities, and by a most surprising method – in the milk of transgenic goats.

Transgenic animals are the results of special biological engineering processes in the course of which extra genes from other animals – often entirely different species – are inserted into their genome. Researchers have been fiddling about with the DNA of different creatures for years. Scientist have inserted into rhesus monkeys and rabbits the gene that makes jellyfish glow in the dark, they've produced chickens that never grow feathers, they’ve made salmon grow up to six times larger than normal, they’ve altered cow and goat milk many times in order to obtain the desired composition, and have accomplished many other similar far-fetched feats. But only recently have they begun to develop large-scale industrial plans for these creatures. And the production of spider silk from goat milk is the best example of a certain plan to industrially produce an exceptional, but very useful thing by means of biotechnology.

As a matter of fact, Nexia's project is less about altering nature than harnessing it. And, if it does succeed – which seems very probable – the product, called "BioSteel" may soon be used for a variety of applications, from medical sutures to bulletproof vests to space stations. The process may also mark an outstanding stride toward the production of other biomaterials, and the commencement of a new kind of technical and industrial revolution – one based on the use of organic processes instead of minerals.

Spider web silk has an average tensile strength of 300,000 pounds per square inch and is both stronger and lighter than compounds based on steel or petrochemicals. The exceptional properties of spider silk have long been recognized. Experienced old fishermen in India have always appreciated its outstanding quality that has had a particular value in the production of fishing nets. American Civil War soldiers frequently used spider web as surgical dressing. The eternal problem, however, has been its dearth, from which stems the great interest of being able to produce it in sufficient quantities, perhaps the way the ancient Chinese learned to “harvest” silk from silkworms.

However, the grand plan to collect spider silk has one small hitch – whereas silkworms are tame herbivores, content with dwelling in close quarters and munching mulberry leaves, thus being submissive subjects of animal husbandry, spiders are aggressive territorial predators that need plenty of space and resist socialization. They always vehemently attack and eat each other if placed in contact or in close proximity. Thus, if you put a bunch of them together, soon you’ll probably end up with only one big, fat, happy spider. And that is the very reason why all attempts to domesticate spiders have failed miserably. However, farming amiable goats is a cinch.

Biotechnology researchers have tried producing spider silk the way they produce medically useful proteins such as human insulin. This involves inserting the gene for the desired material into bacteria, which consequently synthesize the desired proteins in their normal vital course at a fairly good rate. But that produced only a gooey substance with little similarity to the natural product, and no commercial value.

Now, researchers at the Quebec-based Nexia along with scientists at the U.S. Army's Soldier Biological Chemical Command (SBCCOM) in Natick, MA, say they may have figured a way out of the sticky situation. The actual solution consists of inserting the spider genes that code silk structure into the DNA of milk animals. Although there is no general anatomical similarity between spiders and goats or cows, and combining their genomes seems patently outlandish, there is, in fact, an absolutely logical scientific background. The pivotal point is the fact that, unlike the case in the “Spiderman” movie, no fictional and spine-chilling mutations are going to take place – the genes taken from spiders will only express themselves in the mammary glands of these animals. And this is more than logical, as there are very close anatomical similarities between the silk-producing glands of spiders and the milk-producing glands of ruminant animals. It’s just that, when evolution figures out a way of doing something, it often does that with slight variations in many different species. Thus, actually, female mammals are nature's protein factories, inasmuch as milk production is basically protein synthesis. And that is why the goats represent a promising new avenue in the controversial field of transgenic bioengineering.

The scientists' first efforts in the laboratory involved splicing the spider-silk gene into cells taken from the mammary glands of large animals. The silk genes worked with amazing efficiency in the mammary cells, and Nexia scientists were soon producing high-quality spider silk through cell culture. They then produced a line of transgenic mice to see how it would work in living animals.
That experiment also succeeded. The next step was to get the gene into some full-size milk-producing animals. They selected a type of African goat known for its ability to begin reproducing and lactating at an early age (as early as three months after birth). All the transgenic goats are supposed to join a special menagerie of genetically engineered animals, many of which produce proteins in their milk.

The entire procedure seems rather simple, though all the work needs painstaking attention. The spiders are frozen in liquid nitrogen, and then ground into a brown powder. Since every cell of a spider contains the precious silk-producing genes, it's easy to extract them. These genes are then tested in the “Charlotte machine”, what scientists call a “synthetic goat” that tests whether or not the gene will function inside an actual goat. Next, the gene is altered. A “genetic switch” is added, which programs the gene to “turn on” only inside the mammary gland of its new female host during lactation. The altered gene is then pushed on a fine glass pipette into a goat egg. The baby goat will have a spider gene present in each of its cells (its eyes, ears and hooves will all be part spider), but only in the mammary glands of female goats will the silk gene actually spring to life. The goat will eventually start lactating a kind of silk-milk mixture, which looks and tastes just like normal milk. This milk is first skimmed of fat, and salt is added to make the silk proteins curdle into thin whitish particles that promptly sink to the bottom. After the residue has been removed from the milk, a little water is added to this sediment until it turns into a golden-tinged syrup. This silk concentrate is known to scientists as “spin dope” and is more or less identical to what is inside a spider's belly. Now completely stripped from its milky context, the syrupy raw silk is ready for spinning.

The next challenge comprises the procedure of pure silk protein extraction from the milk and its spinning into fabric by processes roughly comparable to the way artificial fabrics are manufactured from petrochemical solutions.

The spin dope is extruded through a tiny aperture at the end of a device that looks like a syringe and into another solution of methanol, prompting the proteins to align and form crystals spontaneously, assembling into fibers that are lighter, yet tougher than Kevlar, and nearly as elastic as nylon. By playing with the production conditions, or adding a second spider protein, they hope to achieve the flex of natural silk.

Naturally occurring spider silk is widely recognized as the strongest, toughest fiber known to man. It is a science wonder, a self-assembling, biodegradable, high-performance, nanofiber structure one-tenth the width of a human hair that can stop a bee traveling at 20 miles per hour without breaking. Spider silk has long been admired by material scientists for its unique combination of toughness, lightness and biodegradability. Dragline silk, which comprises the radiating spokes and serves for anchoring the spider webs, just 3 microns thick, is roughly three times as tough as DuPont's bulletproof Kevlar, stretches better than nylon and, weight for weight, is five times stronger than steel. A woven cable as thick as your thumb can bear the weight of a jumbo jet. These incredible qualities are the product of 400 million years of evolution, and have incontrovertibly dwarfed man’s achievements in material science to date. And, now spider yarn has been spun by Nexia Biotechnologies of Montreal, marking a milestone in efforts to ape arachnids.

Spider silk is ultra strong, light, elastic and biodegradable – simply ideal for everything from surgical sutures to body armor. Since it is compatible with the body, the first uses of BioSteel will probably be in microsurgery for super-thing biodegradable sutures, and then, possibly, for the production of artificial tendons or ligaments. Medicine could also apply it for hemostatic dressings. Fashion’s another thing that could benefit. Farther down the line, it might be the stuff of bulletproof vests lighter and stronger than those currently in use, parachute cords, aircraft and automobile material, the coatings of space stations, perhaps even in bridges or other structures.

It is of course a bit early to know where this will lead, but we live in fast-moving times when technological changes often leap ahead of the most optimistic imagination. Clearly it advances a new field of biotechnology – biomaterials – which could be not only commercially viable but also have more appeal to environmentalists than some other biotechnology products, since spider silk is both a renewable resource and a biodegradable material. In some ways this work recalls the dreams of the social philosophers of the early 1900s, who speculated about a shift to "biotechnical" industries in which biological production systems would replace the inorganic machines of the factory and end (or at least reduce) reliance on mineral-based materials.

By Denis Dilion

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