Did you enjoy learning about the Gila monster last week? I’m still in a Halloween mood. Let’s talk about spiders.

First, I must confess I love spiders. They are such wonderful engineers. Did you know that, as they are spinning their web threads, they can modify the diameter, flexibility, recoil, tensile strength, and stickiness of each thread? Thus, the structural, weight-bearing parts of the web are quite strong (ounce for ounce as strong as the cables that stop jets landing on aircraft carriers), and the insect catching parts are very sticky and elastic, so bugs landing there don’t just bounce off, but are trapped. The web shape each spider makes is genetically determined. I once sat at a tennis match and watched a spider making a new web in the bleachers; more interesting than the tennis match itself. Enough, enough! Let me tell you why spiders are great Halloween monsters. It’s their venom!

Spiders have had over 300 million years to perfect their venom. Almost all spiders are venomous, but most of them aren’t dangerous to humans. Most spider venom just doesn’t bother humans, and many spiders have tiny mouths that can’t penetrate human skin. Out of 50,000 known species of spiders, only about 25 have venom capable of making humans sick. You North American readers of my blog have little to worry about. Only the Black Widow and the Brown Recluse are venomous where we live.

Spider venom is a treasure-trove of chemical compounds, as spiders use their venom to kill prey (mostly insects) as well as for defense from predators (also mostly insects). Since spider venom is so good at killing insects, specific compounds from the venom have been altered to create effective insecticides, such as Spear, a bioinsecticide that is safe for pollinators and mammals.

University of Queensland’s Professor Glenn King has a fascination with venom, and his lab houses the most extensive library of venoms in the world, including samples from more than 600 species of spiders, scorpions, centipedes, and assassin bugs. He is particularly fond of the Australian K’gari funnel-web spider, a spider all Australians have been taught to fear and avoid. Its venom has more than 3,000 components, making it “probably the most complex chemical arsenal in the natural world”, King says.

Many spider venoms (like the K’gari) target ion channels, modulating receptors in the nervous system and muscles. This specificity has led to research using venom extracts to minimize brain damage after strokes. Here’s how it works. Ischemic strokes happen when a clot forms, blocking blood flow in part of the brain, starving those brain cells of oxygen. Our current treatment is based on rapid administration of tPA, a “clot buster”, which restores circulation to those cells. However, tPA only works if given within 3-4 hours of stroke onset. Professor King’s team of researchers at University of Queensland Institute for Molecular Bioscience has been studying the venom of the K’gari funnel-web spider. A specific peptide (protein) in the venom, Hi1a, targets another process that is going on during a stroke. Once an ischemic stroke occurs, and the cells lose blood flow, lactic acid is produced, and the pH drops. This drop in pH activates an acid-sensing ion channel ASIC1a, leading to cell death. The spider venom peptide Hi1a blocks the ASC1a ion channel, preventing the acid-induced cell death. Pre-clinical trials in mice have shown that Hi1a can protect brain cells and reduce brain damage by up to 80% when given even as late as eight hours after a stroke. This is exciting because most stroke patients arrive at the hospital outside the short window of time when tPA can help. Additionally, Hi1a may also help the other type of strokes, hemorrhagic strokes (involving bleeding in the brain rather than a clot). None of this is ready for prime time yet, but Phase 1 human clinical trials have started with a Hi1a nose spray!

Dr King’s K’gari venom research is also leading to possible treatments for Dravet syndrome (a rare, life-threatening form of epilepsy in infants), and other types of epilepsy. His research has also led to a possible venom-based treatment for the abdominal pain of irritable bowel syndrome. Thanks, K’gari spider!

Researchers at the Victor Chang Cardiac Research Institute in Australia have collaborated with Dr King’s team, and are testing the same ion channel principle of the K‘gari venom in heart attacks. When a coronary artery is blocked by clot or spasm, the same cell death process we just talked about in stroke, begins in the heart muscle. Hi1a has been also found to bind to damaged heart muscle cells after heart attacks, blocking the ion channel “cell death message” and averting tissue damage. Their four-year human trials have just begun, evaluating a medication that could be given to heart attack patients by first responders, thus minimizing heart muscle damage. Thanks again, K’gari spider!

Early research looks promising for developing a non-narcotic pain medication from chemicals from tarantula spider venom, utilizing similar ion channel properties.

None of these drugs are ready for prime time yet, so don’t start your spider-breeding facility yet! And they say dogs are man’s best friend!