The same biological compounds that spiders use to paralyze their prey may help save human lives one day.
These eight-legged arachnids—along with scorpions, centipedes, and a handful of other insects—have evolved over hundreds of millions of years to make highly potent venoms that immobilize or kill their meals. Unlike snake or lizard venom, poisons from these tiny creatures target the central nervous system,the part of the body that controls movement.
More specifically, insect and arachnid venoms tend to make ion channels malfunction. These channels are like the chemical locks on the body’s cell-communication canals: They need to open and close in order for cells to send and receive charged particles, which starts off the electrical signaling process between cells. This inter-cellular dialogue eventually leads up to controlling vital biological processes and muscle movement. If the ion channel locks stay open or closed at the wrong intervals, however, they can cause convulsions, paralysis, or other kinds of neurological miscommunications, some of which are ultimately fatal.
Compared to spiders, we’re massive. In all but four cases, the amount of venom a spider can give us with a single dose isn’t enough to kill us (the recluse, black widow, Brazilian wandering spider, and funnel web spider are the notable exceptions). Even better, these venoms may be able to help us. Glenn King, a molecular biologist at the University of Queensland in Brisbane, Australia, and his team study these neurological venoms, and believe they could to be to treat neurological disorders or complications—conditions like epilepsy, ischemic events like strokes, and even pain management—by changing the way ion channels allow our nerves and neurons to communicate.
Quartz spoke with King about the therapeutic potential of these compounds, and where the field is going in the future. This interview has been lightly edited for content and clarity.
Quartz: How did you first recognize the potential of spider and insect venom as a source for drugs for humans?
King: We didn’t come at this from a drug angle originally. We were looking at spider venoms because we were interested in trying to find environmentally friendly insecticides. We thought “Where would a good place be to look for natural insecticides?” and spider venom seemed like the obvious choice because their main diet is insects. They’ve spent 450 million years trying to evolve venoms that will kill or paralyze them.
Spider venoms turned out to be way more complex than I ever expected. They contain hundreds to thousands of small compounds, and as you wouldn’t be surprised to hear, most of them are actually insecticides.
How could these same compounds help people?
The reason we’re interested in those small venomous arthropods is we’re interested in nervous system disorders where are the underlying problem is an ion channel. During the course of our insecticide work we realized these venoms were full of iron ion channel modification modulators that modulate ion channels in the nervous system.
What are some examples of the drugs you’re researching now?
In all of our three areas of interest, we have molecules that are close to entering preclinical studies that are geared toward clinical trials. We have one antiepileptic drug for a particular epilepsy called Dravet syndrome. We have a stroke drug for protecting the brain after stroke, and we have a molecule we’re developing as an analgesic for chronic pain.
The stroke stuff is really important because there are no drugs for stroke. If you have a stroke now, when you get to the hospital after three or four hours, there’s really nothing that can be done for you. You just have to hope that you recover.
[We’ve found] a molecule that can protect the brain even when it’s given up to eight hours after the stroke. When you have a stroke, the region of the brain where the occlusion occurs loses oxygen. The brain is the biggest consumer of glucose in the body. It burns huge amounts of glucose, and it needs oxygen to do that. When it can’t do that it has to use glycolysis, and the end product of glycolysis is lactate, or lactic acid. Just like a muscle that runs out of oxygen when you’re working out, the brain produces large amounts of lactate after a stroke and so just like your muscle it ends up with lactic acidosis. The brain becomes acidic. We have molecules that stop that process.
We also have an interest in pain and and defensive venoms. What defensive venoms generally do is cause pain.We’ve been using those venoms to ask questions like how do you activate that pain pathway. We published a paper in Nature [editor’s note: Scientific Reports is published by Nature] last year where we used to venom to show us a new ion channel that was involved in the transmission of pain that’s now become a new analgesic target.
Is anyone else looking at venom as a potential resource for future drugs?
I should start by saying there about six venom drugs that are FDA-approved that you can get prescribed for you now. There certainly is a lot of activity in that space in pharmaceutical companies. Merck, Janssen, and Johnson & Johnson are just scouring through spider venoms.
Two [current] clinical trials are really exciting: There’s one from a sea anemone—it’s a peptide and it’s being developed for autoimmune diseases, so things like type 1 diabetes, multiple sclerosis, psoriasis, and lupus. I Phase one clinical trials were completed against multiple sclerosis and psoriasis, and it’s about to enter phase two. The really cool thing about it is it’s not an immunosuppressant or steroid. It would suppress their autoimmune disease but it wouldn’t suppress their immune system, so if patients had a bacterial or viral infection they would be able to respond to it just like you and I could.
The other one is a toxin that, for reasons which we don’t totally understand, happens to like to bind to tumor cells. With brain tumors the real problem is you want to take out the tumor but as little of the healthy tissue as possible. Jim Olson, [a researcher] at the Pediatric Cancer Center in Seattle, has put a fluorescent marker on this toxin, and it lights up the tumor. The surgeons can see exactly where the tumor is. They know exactly what bit to take out so they don’t end up taking out any good brain or leaving any tumor behind because you can see exactly where it is. That’s in phase two as well.
What makes arachnid venom superior to existing synthetically made chemical compounds?
Spiders were around 200 million years before dinosaurs—they’re really ancient. They’ve just been working on these molecules for a very, very long period of time. What we’ve found is that spiders have lots of the same sort of molecules, but infinite variations. They invented combinatorial chemistry probably 400 million years ago.
What spiders do is that they take one particular three-dimensional peptide scaffold. It’s a small structural motif that’s three disulfide bonds. The really cool part about it is that as long as you have that basic architecture of that peptide chain, you can hang anything you want off of it. It’s like having the frame for a house and being able to build whatever you want around it. So you can infinitely change that molecule but keep that beautiful shape and that shape gives it very special properties that make it very stable. It’s really quite amazing.
How do you extract venom from these animals?
You take the spider, and you have to put the fangs inside what would be a centrifuge tube, and then you bring out some electrified forceps. You put them on the fangs and that causes them squirt the venom into the tube.
The reason you put just the fangs into the tube [and not the whole mouth] is because otherwise the spiders would sort of spit out and salivate gastric juices as well, and you don’t want to contaminate the venom. We actually put a little paraffin [wax] over the tube and put the fangs through that so all you get is venom into that tube. For a scorpion, the process is the same except you’re using the tail.
If you get 10 microliters (0.01 milliliters), that’s a good day. With that few microliters you can…get a transcriptome [editor’s note: this is an analysis of all the proteins produced by an animal] and analysis of the entire venom components.
We’re limited in terms of what we can keep and get into Australia [because the country has incredibly strict quarantine laws]. We do have Australian venomous animals, and we have an insect factory within the building where we keep spiders, scorpions, assassin bugs, and centipedes, and we milk them on a very regular basis.
I also have a postdoc who once a year goes overseas and goes on a field trip. He goes around Europe and collects venom. He actually milks these animals on site and brings the venom’s back to Australia.