‘I didn’t mean to hurt you’: new research shows funnel webs don’t set out to kill humans

Funnel webs are considered one of Australia’s most fearsome spiders, but their ability to kill humans is by accident rather than design, our new research shows.

In findings published today, we reveal how the highly toxic and quick-acting venom of male funnel-web spiders is likely to have developed as a defence against predators.

When male funnel-web spiders are young, their venom is potent mainly to insects, which they eat. But once males start searching for a female mate, they must leave the safety of their burrows. That’s when their venom becomes potent to vertebrates such as reptiles and mammals – including humans.

So while humans can theoretically die from a funnel web bite, this is just an evolutionary coincidence – our research suggests the spiders aren’t specifically out to get us.

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Funnel webs are among Australia’s most feared spiders. Shutterstock

Why so deadly?

About 15% of all animals use venom for reasons such as to kill or immobilise prey, self-defence or to gain advantage over competitors, such as during breeding season. As an animal matures and its activities change, so too can its venom.

Australian funnel webs are among a small group of spiders whose venom can kill humans. However all 13 recorded deaths occurred before anti-venom was introduced in 1981.

Funnel web venom is lethal because it contains a type of neurotoxin called “delta-hexatoxin”. This toxin can kill humans by attacking the nervous system, keeping nerves “turned on” and firing over and over again. In severe cases the venom can cause muscles to go into spasm, blood pressure to drop dangerously, coma and organ failure, and ultimately death – sometimes within a few hours.

Scientists have long been puzzled by why these toxins are so deadly to humans, when we and other primates have never been funnel web prey or predator. Scientists were also perplexed as to why male funnel webs appeared to have much deadlier venom than females, and caused most human deaths.

However we did know most funnel web bites in humans occur during the spiders’ summer mating season, when the male spiders rarely feed. This suggested the venom played a defensive role.

Venom from a male funnel web spider can kill vertebrates, including humans. David Wilson

Spider sleuthing

We set out to solve this mystery, using molecular analysis of the venom. Although 35 species of Australian funnel-web spiders were officially recognised, only nine delta-hexatoxins from four species had previously been identified. Our analysis increased the number of known delta-hexatoxins to 22, from the venom of ten funnel-web species.

Having this extra data helped us paint a much clearer picture of the venom’s story. It all comes down to natural selection – the process where organisms best adapted to their environment survive and procreate. The genes responsible for this success are preserved and carry on to the next generations, driving the process of evolution

Our data revealed how natural selection triggered a change in the venom of adult male funnel webs. When males sexually mature, they leave the safety of their burrow and wander considerable distances to find a female. This puts male funnel web spiders in the path of vertebrate predators. These can include reptiles (such as lizards or geckos), marsupials (such as antechinus and dunnarts), mammals (such as rats) and birds.

When funnel-web spiders evolved millions of years ago, toxins in its venom mainly targeted their natural prey: insects such as cockroaches and flies. We examined the genetic sequences of all delta-hexatoxins in funnel web venom. We found over time, the venom of adult males evolved to be potent to vertebrate predators. Unluckily for humans, who are vertebrate animals, we copped it in the process.

Female funnel webs stay safely in their burrows and let the males come to them. So the venom of females is thought to remain potent only against insects their entire lives.

Female funnel webs stay in their burrows, so are less likely to be eaten by predators. Shutterstock

Take comfort

Now armed with a stronger understanding of how delta-hexatoxins evolved, we want to put that knowledge to use. The new genetic sequences we discovered will enable a better understanding of what funnel web spider venom does to the human body. This could be critical for improving existing anti-venoms, and for designing evidence-based treatment strategies for bite victims.

We’re not just looking at the venoms of sexually mature males. We’re also examining female funnel-web venom, hoping their insect-specific toxins will lead to new types of insecticides which are less harmful to non-target insects and the broader environment.

Funnel webs may be one of Australia’s most deadly spiders. But perhaps its some comfort to know their venom is not targeted against us, and the potential lethal effects are just a stroke of evolutionary bad luck.

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By Bryan Fry / Associate Professor, School of Biological Sciences, The University of Queensland

Overview

Venoms play a range of adaptive roles in the animal kingdom from predation to defense to competitor deterrence. Remarkably, despite their biological importance and uniqueness, the evolution of venom systems is poorly understood. New insights into the evolution of venom systems and the importance of the associated toxins cannot be advanced without recognition of the true biochemical, ecological, morphological and pharmacological diversity of venoms and associated venom systems. A major limitation has been the very narrow taxonomical range studied. Entire groups of venomous animals remain virtually unstudied. My research is inherently interdisciplinary, integrating ecological, evolutionary, and functional genomics approaches in order to understand the evolution of venom systems. Studies range from discovering the shock-inducing hypotensive and anticoagulant venom of the iconic Komodo Dragon through to exploring the unique temperature specific adaptations of Antarctic octopus venoms.

Qualifications

Doctor of Philosophy, The University of Queensland
Publications

Journal Article: Weaponization of a hormone: convergent recruitment of hyperglycemic hormone into the venom of arthropod predators
Undheim, Eivind A. B., Grimm, Lena L., Low, Chek -Fong, Morgenstern, David, Herzig, Volker, Zobel-Thropp, Pamela, Pineda, Sandy Steffany, Habib, Rosaline, Dziemborowicz, Slawomir, Fry, Bryan G., Nicholson, Graham M., Binford, Greta J., Mobli, Mehdi and King, Glenn F. (2015) Weaponization of a hormone: convergent recruitment of hyperglycemic hormone into the venom of arthropod predators. Structure, 23 7: 1283-1292. doi:10.1016/j.str.2015.05.003

Journal Article: Ancient venom systems: A review on cnidaria toxins
Jouiaei, Mahdokht, Yanagihara, Angel A., Madio, Bruno, Nevalainen, Timo J., Alewood, Paul F. and Fry, Bryan G. (2015) Ancient venom systems: A review on cnidaria toxins. Toxins, 7 6: 2251-2271. doi:10.3390/toxins7062251

Journal Article: Evolution of an ancient venom: recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone
Jouiaei, Mahdokht, Sunagar, Kartik, Gross, Aya Federman, Scheib, Holger, Alewood, Paul F., Moran, Yehu and Fry, Bryan (2015) Evolution of an ancient venom: recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone. Molecular Biology and Evolution, 32 6: 1598-1610. doi:10.1093/molbev/msv050

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Grants

Imaging the world of miniature venomous arthropods
(2014–2017) ARC Linkage Projects

A sensitive, high resolution QTOF mass spectrometer with nanoUPLC system for qualitative and quantitative biomolecule analysis.
(2014–2015) UQ Major Equipment and Infrastructure

Beyond genomes, transcriptomes and proteomes: high throughput analysis of gene and protein expression and function
(2014–2015) UQ Major Equipment and Infrastructure

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Supervision

Centipede Venom Evolution: Casting light on a neglected group of venomous animals
(2014) Doctor Philosophy

Investigation of origin of toxin proteins in Heloderma venom and identification of toxin proteins novel isoforms
Doctor Philosophy

Evolution and diversification of the Cnidarian venom system
Doctor Philosophy

By Volker Herzig / Associate Professor, University of the Sunshine Coast

Associate Professor Volker Herzig is an ARC Future Fellow and his lab is focussed on the biodiscovery of novel arthropod venom components, particularly peptides, for potential applications in basic science, medicine and agriculture. Associate Professor Herzig has compiled the world's largest arachnid venoms collection (currently comprising 550 spider and 150 scorpion venoms) that is already used in a variety of collaborative projects spanning the following areas:

Toxins as bioinsecticides or antiparasitic agents
Toxins as therapeutics
Toxins as tools
The main focus of his lab are bioinsecticides. The agricultural sector is plagued by many pests and parasites causing significant economic damage. Fortunately, some arthropod toxins are selective and potent modulators of ion channels and receptors in the insect nervous system, which aids in overcoming prey or fending off predators. By studying the interaction of arthropod toxins with their molecular targets, Associate Professor Herzig is hoping to discover novel and environmentally safe bioinsecticides and antiparasitic agents.

A future area of research that he will embark on at USC is to investigate how venom toxins modulate learning and memory in insects. This might not only lead to novel tools for controlling insect pests and parasites, but it could even provide a more general understanding of the molecular processes underlying learning and memory.

(Source: theconversation.com; September 22, 2020; https://tinyurl.com/y4s6pxbu)
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