along came a spider

A few weeks ago, I mentioned that Jen-Luc Piquant had recommended a mixture of honey and sugar paste as a homeopathic alternative treatment for my poor wounded knee. It's a time-honored folk remedy that dates back to ancient Sumeria, is mentioned in the Talmud, and was recommended by Hippocrates (we suspect he owned a bee farm). It's true that honey is naturally antibacterial, formed when bees swallow, digest and then regurgitate nectar collected from flowers, in the process adding a critical enzyme that makes hydrogen peroxide. But  scientists have yet to identify the active components that makes the magic happen. I'm skeptical of alternative treatments as a general rule, so I opted for my usual Neosporin ointment, and it worked just fine. However, sometimes conventional antibiotic treatments -- even prescription strength ones, not just over-the-counter products -- simply aren't sufficient to beat back serious infections, particularly as bacteria continue to mutate and become more and more resistant. So more and more medical practitioners are rooting around for promising alternatives, fostering a renewed interest in the efficacy of things like honey.

I was intrigued by last week's article at Wired News detailing the experiences of Jennifer Eddy, a doctor and professor at the University of Wisconsin School of Medicine and Public Health, who has dressed particularly stubborn infected wounds with honey-soaked gauze, with excellent results. One elderly patient was on the verge of having his foot amputated (having already lost two toes) after drug-resistant bacteria reduced it to an icky black rotting mess. The honey-soaked gauze treatment  beat back the infection within a few weeks, and a year later, the patient could walk again.

Of course, it's one thing to compile a compelling collection of anecdotal evidence; it's quite another to prove honey's antibiotic effectiveness via rigorously designed double-blind studies. Eddy knows this. In Germany, doctors at two dozen hospitals are experimenting with the use of honey to treat wounds, along with other medical practitioners in the UK, Australia, and New Zealand. It's less common in the US, but Eddy is conducting the first double-blind study of the treatment in hopes that honey could provide a solution to antibiotic resistant "superbugs" like staphylococcus aureus (MRSA), which causes more than half of all skin infections in US emergency rooms every year, and is becoming a serious problem in athletic locker rooms as well.

Just in case honey doesn't quite do the trick, we might have another option in, um, maggot juice.  Last week, New Scientist reported that the enzymes contained in the fluids produced by maggots can speed up the wound healing process. Really, you can't make this stuff up. It was news to me that live maggots are sometimes applied to chronic wounds because they eat dead tissue but pass on the healthy tissue. What's next, the re-emergence of leeches as a valid medical treatment? Well, yes -- clearly we are behind the times. And now researchers at the University of Nottingham in the UK are developing a tissue-regenerating wound dressing infused with maggot enzymes, by way of a spin-off company, AGT Sciences, although an actual commercial product is at least three years from market.

Should you find the notion of maggot enzymes just a bit too repulsive, there's also the possibility that a hefty dose of "webicillin" could beat back that stubborn infection. Scientists have known for ages that spider silk (especially the dragline silk spun by the golden orb-weaving spider, a.k.a., Nephila clavipes) is pretty amazing stuff. It's incredibly strong -- ounce for ounce, it's stronger than steel or Kevlar, although not as strong as fibers spun from carbon nanotubes. And it's waterproof, and incredibly stretchy, able to stretch 30-40% before it breaks, compared to 8% for steel fibers and around 20% for nylon fibers. But who knew -- other than perhaps Spiderman -- that it also had antimicrobial, blood-clotting, and other wound-healing properties? 

Well, one person who suspected as much was George Emery Goodfellow, a 19th century physician in Tombstone, Arizona, who witnessed a pistol duel between a couple of cowboys in 1881. He examined the body of the unfortunate loser, whose chest had been pierced by two bullets. But there wasn't a single drop of blood oozing from either bullet hole. There was, however, a silk handkerchief protruding from the chest wounds, and when he pulled it out, there was a bullet embedded in it. The bullet went through the other clothes, flesh and bone, but somehow couldn't make it through the silk fabric. Intrigued, Goodfellow starting documenting other cases of silk garments that could stop speeding bullets, collected in an essay entitled, "Notes on the Impenetrability of Silk to Bullets." In one memorable instance, a man wore a silk bandanna around his neck which kept a bullet from piercing the carotid artery.

Research on these more puzzling medical properties has been infrequent at best; mostly, scientists have focused on explicating the tensile strength and elasticity of spider silk. Here's what we know so far. Thanks to special glands located in the abdomen, spiders secrete a fluid protein containing lots of fibers, similar in structure to keratin, the protein found in hair and horns. The silk hardens ("polymerizes") as it oozes; scientists aren't entirely sure what activates this process. They have managed to identify the seven amino acids that make up the silk proteins: it's primarily alanine and glycine, with lesser amounts of glutamine, leucine, arginine, tyrosine, and serine.

In terms of structure, spider silk is pretty intricate. There are rigid layers to hold the silk together, soft areas to keep it flexible, and within those soft areas, places that enable the silk to stretch. Want a few more specifics? Two alanine-rich proteins embedded in a jelly-like polymer make up the fiber, per NMR analysis of the structure. One of these proteins has a highly ordered structure, while the other has a less ordered structure, but both adhere to a glycine-rich polymer that makes up most (70%) of the material. It's this weird blend of order and disorder that gives dragline spider silk its unique combination of strength and elasticity. In fact, a collaboration of scientists in Rennes, France, and Oxford, England have determined that spider silk exhibits behavior similar to certain smart materials (e.g., the Ni-Ti alloy Nitinol) known as shape memory alloys. This property is what makes spider silk so resistant to twisting and swinging. It stabilizes the spider as it suspends itself, and also makes the insect less perceptible to predators.

Scientists care a great deal about refining their understanding of spider silk's complex structure. Gain a sufficiently fine understanding of, and control over, said structure, and scientists would be able to make better artificial silk in the laboratory, with no need for the traditional labor-intensive (and expensive) method of "milking" spiders (essentially pulling out the threat from the spinners by hand). Some 1.3 million spider cocoons are needed to produce a mere kilogram of silk, which is why a lot of commercial-grade silk comes not from spiders, but silkworms, because they're easily farmed; spiders aren't community-oriented creatures and if you put two or more of them together in close quarters, eventually one will eat the other(s).

Making artificial spider silk has not been an easy process. Scientists have made great strides in recent years in terms of determining the fiber's molecular structure and architecture, and even in sequencing the genes. Chemist Glenn Elion of Plant Cell technologies (Chatham, MA) and his colleagues have isolated the entire dragline silk gene sequence -- some 22,000 base pairs in all. As of 2001, the sequences of silk from 14 species had been decoded, and in 2005, biologists at the University of California, Riverside, managed to determine the molecular structure of the gene for the protein used by female spiders to make their silken egg cases.

However, spinning the raw synthetic proteins into a usable thread is a bit more challenging. Spiders have ingeniously designed "spinnerets": usually three pairs of spinners (small tubes connected to specific glands), each with its own function. These spinnerets enable spiders to apply sufficient physical force to the protein fluid to rearrange its molecular structure into silk. We lack similar effective instrumentation, although again, there has been some progress. A Canadian biotech company called Nexia managed to produce spider silk in two genetically altered goats named Webster and Pete, but failed to spin it into silken fibers by pressing the protein solution through small extrusion holes designed to simulate the spinnerets.

However, Randolph Lewis is a molecular biologist at the University of Wyoming in Laramie, who's had a bit more success. He managed to clone parts of genes found in dragline spider silk and implant them in E. coli bacteria. The E. coli then produced silk protein in a fluid solution, which he was able to "spin" into synthetic fibers by squeezing it through a very thin tube. Scientists at the US Army Research, Development and Engineering Center in Natick, Massachusetts, have adopted a similar gene-based approach to make their own genetically cloned polymer fibers. Ditto for Elion and a few of the chemists at DuPont, most notably biophysicist Kenn Gardner. They're still working out how, exactly, to mimic the way spiders adjust the properties of their silk, probably by expressing different genes in different glands -- apparently, different genes produce proteins that contain differing amounts of crystalline material, which alters the silk thread's structure in subtle, yet significant ways.

Naturally, scientists would like to be able to fine-tune the properties of synthetic spider silk in a similar fashion, tailoring it to specific applications. MIT researchers have made synthetic fibers that are both soft and stretchy, like spider silk, and are now adding nanoscale particles to the mix, designed to bind to very specific regions to reinforce the soft material and increase its strength. Eventually, the hope is this material can be used to make garments that don't tear very easily. Weaving in other materials that absorb sweat and wick away moisture would open up even more applications, especially for he military, police, and emergency care workers.

Historically, spider silk has been used as fishing line by Polynesian fishermen, while certain New Guinea tribes used webs as water-repellent hats. During World War II they were used as hairs in measuring equipment, and Americans used threads from Black Widow spiders in their telescopic gun sights. Modern uses span an even broader application range, most notably the manufacture of wear-resistant shoes and clothing; stronger ropes, nets and parachutes. Other future uses could include strong, tough paper that can't be torn, ideal for banknotes, as well as bullet-proof vests for soldiers and policemen. And here's an unexpected application area: scientists at the University of California, Riverside, are exploring ways to use threads of spider silk to make hollow optical fibers for ultrafast nanoscale optical circuits, or to boost the resolution of optical microscopes.

Medical applications haven't received nearly as much attention, but spider silk (natural or synthetic, if scientists continue to progress in their ability to replicate its properties) could be used for tougher sutures, antibiotic bandages, artificial tendons and ligaments, and scaffolding support for weakened blood vessels. In fact, wrapping implants in spider silk might keep the body from rejecting them, since the substance doesn't appear to provoke the usual immune response to foreign objects

Who knows? One day you might find yourself treating oozing open wounds with gauze bandages woven out of spider silk, with no need for hydrogen peroxide or neosporin -- or honey, or icky maggot juice, for that matter. Or you can just make like Homer Simpson (per the fun folks at Frink Tank) and down gallons of the new food-grade ethanol that supposedly "takes just like vodka." I'd bet it's guaranteed to numb those pesky pain receptors, obliterate lingering germs, and most likely kill off a large number of brain cells in the process. But if you're drinking straight ethanol based on a blogger's suggestion, chances are you weren't using many of those brain cells to begin with....

Comments

[Blake Stacey]

No one I know has been able to drink more than a bottlecapful of pure ethanol in one go. Yes, I know people who've tried. . . .

[JScarry]

"Modern uses span an even broader application range, most notably the manufacture of wear-resistant shoes and clothing; stronger ropes, nets and parachutes." This statement intrigued me, so I started looking for examples. I found lots of statements on te web that are similar to this one, but all of them start our with 'If we could make spider silk". Given that it takes millions of anti-social spiders to make a kilogram of silk, it seems unlikely that any commercial poducts exist. Does anyone know of products that currently use spider silk?

[The Science Pundit]

You forgot to mention that tarantulas produce silk from their feet. Is it possible that Peter Parker was bitten by a radioactive tarantula?

http://www.sciencedaily.com/releases/2006/09/060927201410.htm

[JScarry]

"honey and sugar paste as a homeopathic alternative treatment" As they say in The Princess Bride, I don't think that word means what you think it means. If it was homeopathic it would be diluted until there was nothing there. I'm not up on the alternative-woo but the right word might be "holistic" or "naturalistic".

[Blake Stacey]

@JScarry:

Maybe "all-natural"? (You know, like deadly nightshade.) Or, how about "organic"? To quote my old college pal Dylan Stiles,

> I have always found the phrase "organic chemistry" somewhat ironic, because the word organic usually conjures up
> images of extra-crunchy Trader Joe's all-natural granola. But the reality of an organic chemistry lab is that
> it's filled with the nastiest, most toxic substances known to mankind.

http://archive.tenderbutton.com/?p=75

(Yes, he **is** the fellow who did the NMR of his own ear wax. He's moving on from blogging to write a regular column for **Chemistry World**, leaving the blogosphere a little poorer in his wake.)