by Joseph DeSisto
Poisons and venoms often contain hundreds of different chemicals, each with a special role. When venom is dangerous to humans, it is useful to know which of the molecules involved is causing harm. In the case of the blue-ringed octopus, tetrodotoxin is the culprit, paralyzing your nervous system and keeping you from breathing. Cobras and sea snakes accomplish roughly the same thing with a whole suite of neurotoxins. Vipers, on the other hand, use hemotoxins to destroy blood vessels and force clots to develop, so oxygen can’t reach the cells that need it.
Brown recluse venom is far less dramatic. As in all spiders, the primary purpose of venom is to kill and digest insects or other prey, but recluse spiders and their relatives (members of the family Sicariidae) have a protein that does something special. That protein is called sphingomyelinase D – we’ll call it SMD. Exactly what SMD does when injected into insects isn’t clear, but when it enters a person via a spider bite, the protein may cause the tissue around the bite to die and form a necrotic lesion. In extremely rare cases, SMD can be carried by the bloodstream to other parts of the body, causing illness or even death.
Recluses and their cousins, the sand spiders (genus Sicarius), belong to the family Sicariidae or six-eyed spiders, which includes all the 132 spiders that use SMD in their venom (Binford and Wells 2003). No other animals are known to produce SMD, but there are bacteria that make it, and it just so happens that all of these bacteria are known to cause infections in humans (Binford et al. 2005).
One of them is Clostridium perfringens. Chlostridium is a genus of bacteria with around 100 species, all but five of which are completely harmless. See the layer of dust at the back of your desk? Run your finger through it – write your name, or make a smiley face. Now look at the dust that’s gathered on your fingertip. Chances are you’ve just collected some Clostridium, which is also found in soil, water, plants, and the digestive systems of animals. Clostridium spores are virtually indestructible, so the bacteria can contaminate just about any surface. Since the vast majority of species are harmless, that isn’t much of a problem.
Five, however, can cause serious illness in humans. The best-known is Chlostridium botulinum, which makes a poison called botulinotoxin and causes, as you might have guessed, botulism. C. perfringens, meanwhile, can cause food poisoning and gangrene using, among other proteins, SMD. Here’s where the plot thickens: Brazilian researchers discovered in 2002 that perfringens often lives in the venom glands of recluse spiders, manufacturing SMD alongside the spider’s own arsenal of venom-producing cells (Monteiro et al. 2002).
The same scientists then tested the strength of the spiders’ venom on rabbits, using spiders with and without bacterial “infections.” As expected, spider bites led to bigger lesions when bacterial colonies were present in the spider’s fangs, suggesting these bacteria might actually help the spiders by making their venom stronger. In return, the bacteria get a relatively safe place to multiply, within their host’s venom glands.
Recluse spiders aren’t unique in using bacteria to help manufacture toxins. Pufferfish, for example, wouldn’t be poisonous if it weren’t for tetrodotoxin-producing bacteria that live within their skins and livers. What’s different about the recluse-bacteria relationship is that neither party truly depends on the other – perfringens bacteria can easily find shelter elsewhere, and recluse spiders can make plenty of SMD without the microbial help, thank you very much.
The gene that allows for SMD in both spiders and bacteria reveals that life was not always so. Instead, more than 150 million years ago, an enterprising spider stole the bacteria’s SMD-making genes and inserted them into its own DNA toolkit (Binford et al. 2005). That spider did very well — all of today’s six-eyed spiders, the SMD-producing recluses and sand spiders, are descended from that individual.
Bacteria aside, all recluses are not equally dangerous to humans. The North American brown recluse (Loxosceles reclusa) is relatively tame: bites are very rare, to the point that 80% of alleged recluse bites aren’t actually recluse bites (Swanson and Vetter 2005). A review of “suspected” brown recluse bites revealed that around a third of bite victims developed lesions, 14% fell ill, and none died or suffered serious complications (Wright et al. 1997). The United States is also home to five other recluse species, none of which are known to be harmful to people.
Travel to western South America and the story changes. The Chilean recluse (Loxosceles laeta) is the most dangerous of the recluse species, partly because it likes to live in and around buildings. In Spanish it goes by the name araña de rincón, which means “corner spider,” after this spider’s habit of finding shelter in the secluded, dusty corners of old homes. Even though Chilean recluses are not especially aggressive, their preferred habitats makes encounters with humans very likely, and a few bites each year are inevitable.
Bites from Chilean recluses are also more toxic than those of their northern cousins. A survey of bite cases found that 84% of people developed lesions, 15% fell ill, and 3.7% died (Schenone et al. 1989). A 3.7% death rate sounds pretty scary, but this was in 1989 – medical care has improved since then, and spider antivenom today is much more widely available (Lucas 2015).
Sand spiders also possess SMD and can cause lesions in humans. Yet despite sand spider venom being far more toxic than most recluse venoms (Van Aswegen et al. 1997), no human deaths have ever been reported. Why? Because sand spiders, unlike recluses, don’t tend to live in places where human encounters are likely. Instead they inhabit remote desert regions of South America and Africa. Even though sand spiders have some of the most powerful venoms of any spiders, loaded with SMD, but bites are extremely rare and the worst cases have only resulted in lesions similar to those caused by recluse bites (Lopes et al. 2013)
Millions of years of desert living have hardened the sand spiders – some species can live longer than a decade. Opportunities to catch prey in the desert are rare, so strong venom might help reduce the spiders’ error rate. Sand spiders are also experts at camouflage, often covering their bodies with sand to disguise their bodies in a barren landscape.
So what’s the difference? Why are some recluses and sand spiders more toxic than others? Since among all the proteins in recluse and sand spider venom, SMD is the one that causes harm to humans, it makes sense that spiders with higher levels of SMD in their venom are more dangerous. Specifically, we would expect the sand spiders and the Chilean recluse to have more SMD in their venom than the other, less dangerous recluse spiders. But how to test our theory?
The first step: extracting venom from recluses and sand spiders, which is easier than you might think. Scientists at the University of Arizona (Binford and Wells 2003) did this by knocking out spiders with carbon dioxide, then shocking their fangs with tiny electrodes. The minute electric shock caused the unconscious spiders to release all their venom into tiny vials, which could then be stored in a -80̊ C freezer. The same technique works for extracting venom from all kinds of animals, from rattlesnakes to scorpions to honey bees.
Next comes measuring the SMD levels in venom from each species — in this experiment, ten recluses and two sand spiders. The results were surprising in that the sand spider and Chilean recluse venoms had moderate concentrations of SMD — no greater or smaller than those of the other spiders. Instead, these three differed from the others in another regard.
They had more venom by, on average, nearly seven times. Usually, large spiders have more venom than smaller ones, but all the spiders in this experiment are roughly the same size. Why the sand spiders and the Chilean recluse should have so much more venom than their relatives is unknown for practical purposes, it doesn’t really matter. What matters is that, even if SMD concentrations are about equal, sand spiders and Chilean recluses still have seven times more SMD than any of the other recluses.
Venoms and poisons are bewilderingly complicated. They’re also amazing, and locked within each molecule are incredible opportunities to understand the natural world, improve medical care, and even save lives. When the diversity of life on earth meets the diversity of biochemistry, it’s clear that studying these amazing substances will keep scientists occupied for as long as there are spiders, hiding in corners and striding across the sand.
Thanks are owed to Sean McCann, who gave me permission to use his photograph of an Arizona recluse (Loxosceles arizona), rarely seen in the United States. You can check out more of his photography at his website, http://ibycter.com/.
Catherine Scott, a PhD student and arachnologist at the University of Toronto, maintains a blog devoted to spider biology. She wrote a fantastic article on identifying brown recluses, which you can read here. You can also follow her on twitter (@Cataranea) and inquire about spiders you think might be brown recluses.
Binford G.J., M.H.J. Cordes, and M.A. Wells. 2005. Sphingomyelinase D from venoms of Loxosceles spiders: evolutionary insights from cDNA sequences and gene structure. Toxicon 45: 547-560.
Binford G.J. and M.A. Wells. 2003. The phylogenetic distribution of sphingomyelinase D activity in venoms of Haplogyne spiders. Comparative Biochemistry and Physiology Part B 135: 25-33.
Lopes P.H., R. Bertani, R.M. Gonalves-de-Andrade, R.H. Nagahama, C.W. van den Berg, and D.V. Tambourgi. 2013. Venom of the Brazilian spider Sicarius ornatus (Araneae, Sicariidae) contains active sphingomyelinase D: potential for toxicity after envenomation. PLoS Neglected Tropical Diseases 7(8): e2394. doi: 10.1371/journal.pntd.0002394
Lucas S.M. 2015. The history of venomous spider identification, venom extraction methods and antivenom production: a long journey at the Butantan Institute, São Paulo, Brazil. Journal of Venomous Animals and Toxins Including Tropical Diseases 21: 21.
Monteiro C.L.B., R. Rubel, L.L. Cogo, O.C. Mangili, W. Gremski, and S.S. Veiga. 2002. Isolation and identification of Clostridium perfringens in the venom and fangs of Loxosceles intermedia (brown spider): enhancement of the dermonecrotic lesion in loxoscelism. Toxicon 40: 409-418.
Saupe E.E., M. Papes, P.A. Selden, and R.S. Vetter. 2011. Tracking a medically important spider: climate change, ecological niche modeling, and the brown recluse (Loxosceles reclusa). PLoS ONE 6(3): e17731. doi: 10.1371/journal.pone.0017731
Schenone H., T. Saavedra, A. Rojas, and F. Villarroel. 1989. Loxoscelism in Chile: epidemiological, clinical, and experimental studies. Revista do Instituto de Medicina Tropical de São Paulo 31(6): 403-415.
Swanson D.L. and R.S. Vetter. 2005. Bites of brown recluse spiders and suspected necrotic arachnidism. The New England Journal of Medicine 352: 700-707.
Van Aswegen G., J.M. van Rooyen, D.G. van der Nest, F.J. Veldman, T.H. de Villiers, and G. Oberholzer. 1997. Venom of a six-eyed crab spider, Sicarius testaceus (Purcell, 1908) causes necrotic and haemorrhagic lesions in the rabbit. Toxicon 35(7): 1149-1152.
Wright S.W., K.D. Wrenn, L. Murray, and D. Seger. 1997. Clinical presentation and outcome of brown recluse spider bite. Annals of Emergency Medicine 30(1): 28-32.