Snakebite, antivenom research, and basic science

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In the past few weeks, a peculiar congruence of several seemingly-unrelated events took place. (At least) two new scientific papers about snake biology were published, a new video series was announced, some scientists entered contests, and the U.S. executive branch announced a budget proposal with deep cuts to science funding. However, these events aren't as unrelated at they might seem at first glance, and they have something to tell us about where snake biology, and science in general, are going in the future.

The science: part I (puff adders)

A puff adder (Bitis arietans)

Puff Adders (Bitis arietans) are among Africa's most widespread vipers. They are heavy-bodied snakes that are found in savannas and open woodlands. Like most vipers, they eat mostly rodents as adults, which they ambush from carefully-selected sites, which they sometimes occupy for weeks at a time. Recently, Xavier Glaudas and Graham Alexander published a new study showing that, even though Puff Adder strikes last less than two seconds, they can choose to either hold onto or let go of the prey depending on its size. Specifically, they hold onto small mice, shrews, birds, toads, and lizards, but strike & release larger rodents and rabbits, because retaliatory rat bites are dangerous to them. After they let go of these larger prey, which usually run off a short distance before the venom kills them, they track them down again using stereotypic strike-induced chemosensory searching behavior to locate the scent of non-toxic components of their own venom. This is really similar to findings by Bree Putman and Rulon Clark that Southern Pacific Rattlesnakes (Crotalus oreganus) were more likely to hold onto smaller rodents than to larger ground squirrels. You can watch 26 awesome videos selected from an archive of thousands of hours of video taken in the wild over more than two years.¹

This research matters because venomous snakes and their prey are in constant evolutionary arms races, leading to:

1. a mosaic of new biochemical compounds that are often useful in treating disease
2. a mosaic of new biochemical compounds that can make venomous snakebite really hard to treat

We'll come back to the second one in a minute. The obvious importance of human medicine and venomous snakebite treatment overshadow a third important reason to study snakes and what they eat. Although the beneficial role of snakes in rodent control is taken as gospel by many advocates of snake conservation, the amount of data that we actually have on what snakes eat in the wild is surprisingly small. For many species, we don't even have a general idea of what kinds of prey they like to eat. Given recent estimates that spiders eat about as much meat as people do worldwide, and the potential for snakes to reach very high population densities in certain habitats, it's likely that the top-down effects of snakes as predators are significant ecosystem services that most humans aren't aware of and thus undervalue. Indirect effects on other aspects of the ecology of snake prey species, such as predation release and disease transmission, link snake predation even more strongly to human health. This is particularly timely in light of recent predictions that 2017 will be a big year for white-footed mice and thus for Lyme disease in the northeastern USA, controversy over the reintroduction of Timber Rattlesnakes, one of the white-footed mouse's top predators, to Quabbin Island in Massachusetts², and the continuation of both the infamous Sweetwater Rattlesnake Roundup³ and the reformed Claxton Wildlife Festival and Lone Star Rattlesnake Days earlier this month.

The science: part II (how cobras got their flesh-eating venoms)

A Mozambique spitting cobra (Naja mossambica) spitting its venom

Spitting cobras are even more well-known than puff adders because of their defensive venom spitting abilities, showcased on the BBC's Life in Cold Blood. They are found in Africa and Asia and are thought to have evolved two or three times from non-spitting cobras. A new paper from the lab of Bryan Fry at the University of Queensland sheds some light on when and why venom spitting evolved. Elapid snakes, including cobras, have venoms rich in neurotoxins, which are highly potent toxins that are very effective at paralyzing their prey. Cobras also have less potent cytotoxins that kill cells directly, which is a bit weird. What is the function of these toxins?

Toxicity of snake venom to human cells grown in culture.
Warm colors indicate higher toxicity.
From Panagides et al. 2017

The hypothesis put forth here is that the first step towards venom spitting was the evolution of hooding behavior and morphology, which happened twice in elapids: once in "regular" cobras and once in King Cobras, which are more closely related to mambas. Only once a conspicuous visual display was present was there selective pressure for cytotoxic venom components delivered to the eyes of potential predators via spitting. Although the venom of both groups is cytotoxic, Hemachatus (rinkhals) and Naja cobras use three-finger toxins, whereas King Cobras use L-amino acid oxidase enzymes, consistent with the undirected, opportunistic nature of our current model of venom evolution by gene duplication and mutation. The authors suggest that further elevations in cytotoxicity are linked to bright bands and other aposematic colors or hood markings, although their paper did not attempt to quantify these attributes of cobra displays, which can be quite diverse even within species. Further evidence in support of the hypothesis is that Naja naja and Naja oxiana seem, based on their nested position, to have lost spitting but to have retained cytotoxicity, and their close relatives Naja atra and Naja kaouthia might represent steps down this evolutionary path, being capable of spitting only in some populations and with less accuracy than the African and southeast Asian clades of true spitting cobras.

This is an extremely cool and popular topic. It was covered by IFLS, The Wire, Gizmodo, and the Washington Post. It goes to show that people worldwide are fascinated by venomous snakes, and the Fry lab has done a great job capitalizing on that interest (among other accolades, Fry's graduate student Jordan Debono recently won the Queensland Women in Science Peoples' Choice Award [a contest that was decided by an online popular vote; more on this later] for her research on global snakebite treatments). One reason for this fascination has to do with the question of who, exactly, these cobras are defending themselves from? The most reasonable hypothesis, given the timing and geography of the diversification of spitting cobras and the precision with which they can target forward-facing eyes and hominoid faces, is primates. Us, and our ancestors, who have eaten and been eaten by snakes for millions of years. Studying spitting cobras is a window into our own evolutionary past, a way for us to learn about ourselves. But, let us not be misled into thinking that interactions between humans and cobras are a thing of the past.

The upshot: the truth about snakebite

You can follow the ASV @Venimologie

If you haven't read the blog by medical toxinologist Leslie Boyer, you really should. Earlier this month she wrote about the vicious circle of antivenom shortage in sub-Saharan Africa, where millions of people are bitten by venomous snakes every year, many of which die or suffer awful injuries because they lack access to good antivenom. This crisis has prompted the creation of the African Society of Venimology and a new series of snakebite training videos in English, French, and Spanish. The politics and economics of antivenom are complicated and reflect larger issues in medicine, education, quality control, supply and demand, and how global economics and corporations have failed to respond to the needs of local communities and consumers. In a nutshell, the issue is that antivenom manufacturers don't make enough good antivenom, because not enough people buy it. People don't buy it because it's expensive, and it's expensive because not that much is made. This is despite a huge need for it—but not everybody with a snakebite goes to a hospital and gets antivenom in Africa, partially because it's not certain there will be any and partially because a lot of patients and doctors don't know about antivenom, because it's not in widespread use (which is mostly because of the reasons above). Other exacerbating problems include that it's often not certified, fake products can price the real antivenom out of the market, and the infrastructure for distributing antivenom and information in Africa is sub-optimal (but improving). Fixing any one or even most of these problems won't fix the whole system—if any one of them break down, supply and demand will be out of balance and people won't get the care they need.

A lot of the same issues used to be present in Mexico, but product improvements, government outreach, and massive education efforts in the 1980s and 1990s dramatically reduced mortality from venomous snakebite and led Mexico to become a major producer and consumer of high-quality, affordable antivenom, so much so that the USA now imports some of these drugs from Mexico. The Mexican government enabled the Mexican antivenom industry to be competitive and reach its market, which is much larger than the domestic market for American antivenom manufacturers—medically-serious venomous snakebites (and scorpion stings) in the USA are mostly confined to the southwest, and the per-capita risk of snakebite is the lowest in the world. This creates its own unique problems. You may have heard about the controversy surrounding the discontinued coralsnake antivenom made by Wyeth, and there are compelling arguments that the Mexican polyvalent antivenoms Anavip (made by Bioclon for humans) and ViperSTAT (made by Veteria Labs for cats and dogs) are more effective and much less expensive (although this is due almost exclusively to the idiosyncrasies of the US healthcare finance system) than the only FDA-approved viper antivenom, CroFab (although BTG, the maker of CroFab, filed a complaint asserting that these Mexican products infringe on its patent).

Finally, the global importance of the availability of high-quality, affordable antivenom for Latin American, African, and other exotic snakes is only going to increase as venomous snakes become more popular as pets and in zoos. This is particularly true in parts of the world completely lacking venomous snakes or with only very benign, non-life-threatening species, such as northern Europe, Scandinavia and northern North America, where doctors may be totally unprepared for a snakebite emergency and may not have appropriate antivenom on hand. This is exactly the kind of situation where government funding, in the form of orphan disease R&D grants, could play a role in making it affordable for researchers and doctors to save lives.

For a great introduction to and more in-depth coverage of these issues, you should watch The Venom Interviews or read their coverage of the recent video series.

The future: sequence the Temple Pitviper genome

Temple or Wagler's Pitvipers (Tropidolaemus wagleri)
at the famous Temple of the Azure Cloud in Penang, Malaysia
You can vote to sequence their genome here!

Genomics of snakes is taking off in a big way, and we stand to learn a lot more about the evolution and function of snake venoms and the treatment of their effects. But, funding for basic science isn't a priority for many people, and more and more scientists are turning to crowd-funding their research or relying on limited funding from private foundations, which often decide which projects to fund through a crowd-sourced voting process. This isn't necessarily a bad thing; in fact, I think it's a great thing in many cases. But, it's important to realize that government funding for science is different from private funding in two crucial ways: 1) there is a lot more of it (at least for now), and 2) it's not driven by specific, private interests. A great example is the Orianne Society, a non-profit reptile conservation organization whose founding purpose was preventing the extinction of Eastern Indigo Snakes (Drymarchon couperi). Thanks to generous donations from private funding sources, the Society succeeded in purchasing large areas of critical habitat for this endangered snake and protecting them in perpetuity, probably the most effective and laudable conservation goal in existence. Another good example is the work of the Durrell Wildlife Conservation Trust, who have essentially saved a globally-rare snake, Casarea dussumieri, from extinction in the wild. I wish the quality conservation work that these organizations have become well-known for were more common, but to date their donors are some of the only large private backers of reptile research and conservation in the world.

Snakes are part of human economics, albeit to a lesser extent than many insects, fishes, birds, and mammals—they are hunted for food (although there are many issues surrounding better management of unsustainable harvests), kept as pets, their skins made into leather, and their venom harvested to make antivenom and other drugs. But, in their current form, these industries place very little emphasis on finding out more about snake biology in the wild; it just isn't necessary for them to make a profit, even though the information is important for what they do. Antivenom manufacturers are accountable to their shareholders, but trying to block FDA approval of Mexican antivenom is certainly not going to result in better treatment for snakebite victims in the USA, and American companies aren't investing in any research to create new, better products themselves, since drug development is expensive and risky, and they already have a monopoly on antivenom in the USA.

It's no secret that snakes and snake research have a PR problem: even scientific journals are less likely to publish research articles about snakes than about mammals and birds (although the bias is likely subliminal). Many people prefer cute fuzzy animals that are similar to humans, but research into the biology of un-fuzzy animals is equally important. There's a parallel to the divide between funding for basic and applied science. Basic science isn't usually as sexy as the exciting, fun applications that come later, like saving lives, curing diseases, or discovering new complex biological phenomena. However, important applied science like antivenom creation cannot happen without basic science, in particular basic science on snakes. Private companies can't afford to invest in basic science the way they once did. Which leaves government funding and that from a limited number of interested, private backers.

We should support public funding for science and elect politicians who will do the same; better treatment for snakebite should be the least partisan and most universally-agreed-upon goal in the world. I think the path between basic (snake ecology, venomics, and genomics) and applied (antivenom manufacturing and public health) science is shorter and clearer in this context than in many, but the same principles apply—you cannot have medicine, conservation, and the other good parts of civilization without science.

You can vote now through April 5th 2017 for a project sequencing the entire genome of the Temple Pitviper (Tropidolaemus wagleri) co-led by Ryan McCleary.

Stay tuned for more about the role of snake venom proteins in treating human diseases, and the role of snakes as predators in ecosystems.

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1 Naturally, I wanted to link to the full-text of the paper so that anyone interested in learning more could read it, but the publisher (Wiley) has a 12-month embargo on posting the PDF anywhere online. They actually expect you to pay between $6 and $38 to read the article. Now, I think it's great research, and it probably cost Glaudas, Alexander, and their university thousands of dollars and thousands of hours to do it. But, if you pay Wiley to read their paper, none of that money will go to them, nor to the scientists who peer-reviewed their work for free. It will go to Wiley, who Xav paid (maybe) to publish. They could have paid $3,000 to make it open access, but you can understand why they didn't. No wonder most most science is read by fewer than 10 people. It's an outdated model that can't go away fast enough. In contrast, the spitting cobra paper is open access, which cost its authors over $1,500. This is typical; academic authors almost always lose money on a publication.^↩

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2 Recent update here; you can write the governor of Massachusetts here.^↩

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3 Reports suggest that this year, like last year, a much larger number of live rattlesnakes were collected than markets could support, and at least one person died from a snakebite sustained while trying to capture a rattlesnake for a roundup.^↩

ACKNOWLEDGMENTS

Thanks to Bryan Fry for alerting me in advance of his publication, and to Colin Donahue, Markus Oulehla, and Ian Glover for the use of their photos.

REFERENCES

Bonnet, X., R. Shine, and O. Lourdais. 2002. Taxonomic chauvinism. Trends in Ecology & Evolution 17:1-3 <link>

Boyer, L. V. 2016. On 1000-Fold Pharmaceutical Price Markups and Why Drugs Cost More in the United States than in Mexico. The American Journal of Medicine 128:1265-1267 <full-text>

Boyer, L. V. and A.-M. Ruha. 2016. Pitviper Envenomation Guidelines Should Address Choice Between FDA-approved Treatments for Cases at Risk of Late Coagulopathy. Wilderness and Environmental Medicine. 27:341–342 <full-text>

Boyer, L. V., P. B. Chase, J. A. Degan, G. Figge, A. Buelna-Romero, C. Luchetti, and A. Alagón. 2013. Subacute coagulopathy in a randomized, comparative trial of Fab and F (ab′) 2 antivenoms. Toxicon 74:101-108 <full-text>

Cao, N. V., N. T. Tao, A. Moore, A. Montoya, A. Rasmussen, K. Broad, H. Voris, and Z. Takacs. 2014. Sea snake harvest in the Gulf of Thailand. Conservation Biology 28:1677-1687 <full-text>

Chew, M., A. Guttormsen, C. Metzsch, and J. Jahr. 2003. Exotic snake bite: a challenge for the Scandinavian anesthesiologist? Acta Anaesthesiologica Scandinavica 47:226-229 <full-text>

Chippaux, J.-P. 2012. Epidemiology of snakebites in Europe: a systematic review of the literature. Toxicon 59:86-99 <full-text>

Glaudas, X., T. C. Kearney, and G. J. Alexander. 2017. To hold or not to hold? The effects of prey type and size on the predatory strategy of a venomous snake. Journal of Zoology 10.1111/jzo.12450 <abstract>

Glaudas, X. and G. Alexander. 2017. Food supplementation affects the foraging ecology of a low-energy, ambush-foraging snake. Behavioral Ecology and Sociobiology 71:5 <link>

Margres, M. J., J. J. McGivern, M. Seavy, K. P. Wray, J. Facente, and D. R. Rokyta. 2015. Contrasting modes and tempos of venom expression evolution in two snake species. Genetics 199:165-176 <full-text>

McCleary, R. J. and R. M. Kini. 2013. Non-enzymatic proteins from snake venoms: a gold mine of pharmacological tools and drug leads. Toxicon 62:56-74 <full-text>

Natusch, D. J. D., J. A. Lyons, Mumpuni, A. Riyanto, S. Khadiejah, N. Mustapha, Badiah, and S. Ratnaningsih. 2016. Sustainable Management of the Trade in Reticulated Python Skins in Indonesia and Malaysia. IUCN, Gland, Switzerland <full-text>

Nyffeler, M. and K. Birkhofer. 2017. An estimated 400–800 million tons of prey are annually killed by the global spider community. The Science of Nature 104:30 <full-text>

Panagides, N., Timothy N. Jackson, R. Pretzler, M. P. Ikonomopoulou, Kevin Arbuckle, D. C. Yang, S. A. Ali, I. Koludarov, J. Dobson, B. Sanker, A. Asselin, R. C. Santana, I. Hendrikx, Harold van der Ploeg, J. Tai-A-Pin, R. v. d. Bergh, H. M. I. Kerkkamp, F. J. Vonk, A. Naude, M. Strydom, L. Jacobsz, N. Dunstan, M. Jaeger, W. C. Hodgson, J. Miles, and Bryan G. Fry. 2017. How the cobra got its flesh-eating venom: cytotoxicity as a defensive innovation and its co-evolution with hooding and spitting. Toxins 9 <full-text>

Putman, B. J., M. A. Barbour, and R. W. Clark. 2016. The foraging behavior of free-ranging Rattlesnakes (Crotalus oreganus) in California Ground Squirrel (Otospermophilus beecheyi) colonies. Herpetologica 72:55-63 <full-text>

Stock, R. P., A. Massougbodji, A. Alagon, and J.-P. Chippaux. 2007. Bringing antivenoms to Sub-Saharan Africa. Nature Biotechnology 25:173-177 <full-text>

Wade, L. 2014. For Mexican antivenom maker, US market is a snake pit. Science 343:16-17 <full-text>

Willson, J. D. 2016. Indirect effects of invasive Burmese pythons on ecosystems in southern Florida. Journal of Applied Ecology 10.1111/1365-2664.12844 <full-text>

Willson, J. D. and C. T. Winne. 2016. Evaluating the functional importance of secretive species: A case study of aquatic snake predators in isolated wetlands. Journal of Zoology 298:266-273 <full-text>

Life is Short, but Snakes are Long by Andrew M. Durso is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Even snakes have their charismatic megafauna

This post will soon become available in Spanish.

Bitis harenna
From Gower et al. 2016

Last year, I wrote about the 10,000th reptile and the 3,500th snake species to be described by scientists. The pace has not slowed down—as of its most recent update last week, The Reptile Database currently lists 3,596 species of snakes out of a total of 10,391 species of (non-avian) reptiles. A few weeks ago, the March 21st issue of the frequently-published journal Zootaxa (volume 4093, issue 1) included descriptions of three of these new snake species. What's interesting is that I initially looked this issue up because I saw one of them being shared a lot on social media—a new large species of viper. The other two, a pipesnake and a blindsnake, hadn't received as much attention. Zootaxa tweets all of their new species, and an examination of their feed shows that the viper tweet received 4 retweets and 2 likes, whereas the pipesnake and the blindsnake received 2 retweets and one like each (even though the pipesnake had a photo¹ and was on the cover). Even though that's a small sample size, I think it's telling that even snakes have their charismatic megafauna.

A bongo (Tragelaphus eurycerus, top)
and a tiger (Panthera tigris, bottom).
You only needed a caption for one

It seems backwards, in a way, that the dangerously venomous viper should be more popular than the innocuous pipesnake. One conservation blogger, Corey Bradshaw, put it nicely by saying that "the only thing worse than being labelled deadly is not being called anything at all". Bradshaw pointed out that drawing attention to the potential for a species to cause harm to humans is not necessarily bad for the species in question. Even though snake biologists often decry these claims as exaggerated (usually because they are), Bradshaw wondered whether they are really very harmful. He suggested that people are generally more fascinated with animals that could kill us (even if they rarely do) than they are with entire groups of benign species, such as skinks or plethodontid salamanders, which are often considered boring (if a person is even aware of their existence). Compare tigers with, say, bongos. Both are critically endangered, inarguably gorgeous animals from exotic places. Tigers sometimes kill and eat people. Everyone knows a tiger. Most people think a bongo is a drum. Or, if you want a snake example, take rattlesnakes. Rattlesnakes are the Bald Eagles of snakes. They are distinctly North American. Everybody in North America knows them. One was on our flag. In contrast, the USA has never had a Smooth Greensnake (Opheodrys vernalis) on its flag, even though they are beautiful and North American and eat spiders. Perhaps the idea that any publicity is good publicity applies to conservation as well. Then again, perhaps not—many residents of Massachusetts are needlessly worried about a Timber Rattlesnake reintroduction plan on an island in the Quabbin Reservoir, probably in part because of the bad PR that rattlesnakes get on a regular basis. If the Massachusetts Division of Fisheries & Wildlife were reintroducing Smooth Greensnakes, I doubt that most people would care (and it certainly wouldn't have been the subject of such venomous debate in the media). Indeed, Illinois's Lincoln Park Zoo is reintroducing Smooth Greensnakes in Chicago, and nobody is writing letters to the editor about it (and, in a way, that's a shame, because it's an interesting and worthwhile effort).

Letheobia mbeerensis
From Malonza et al. 2016

Anyway, I wanted to give some well-deserved press to the two less-publicized new snakes. The blindsnake, Letheobia mbeerensis, is pink with tiny, barely visible eyes. It was described from a single specimen collected southeast of Mt. Kenya in April of 2014 by a local farmer, who found it while tilling his fields. This person, whose name was not known to the scientists who wrote the article, made a considerable effort to get the snake identified—he traveled 125 miles from Siakago to Nairobi, where he gave the specimen to the Nairobi Snake Park, who forwarded it to herpetologists at the National Museums of Kenya. It is unique in having a relatively long tail (for a blindsnake), and in being found in a moist inland savanna. The other two Kenyan species of Letheobia, one of which was just described in 2007, are found in coastal lowlands with sandy soils. It is the 24th species of blindsnake known from Kenya, but I can guarantee that it won't be the last.

Historical drawings of Cylindrophis ruffus
Illustrations A-C from Scheuchzer 1735
D-E from Seba 1735
From Kieckbusch et al. 2016

The story of the new pipesnake is even more interesting, and I suspect the paper in which it is described will ultimately be the most read and most cited of the three snake papers in this issue. This is because, in addition to describing the new species, it contains "an overview of the tangled taxonomic history of C[ylindrophis] ruffus", a widespread species commonly known as the Red-tailed or Common Pipe or Cylinder Snake. The fourteen species of Asian Pipesnakes (family Cylindrophiidae) are secretive and semifossorial snakes with small eyes, bodies that barely taper at all, and ventral scales only slightly larger than or equal in size to their dorsal scales. Many have contrasting light and dark ventral blotching with conspicuous bright coloration on the underside of their short tail, which they expose when threatened. Scientific knowledge of these snakes predates modern biological nomenclature. One is pictured in Albertus Seba's Thesaurus, which was one of Linnaeus's main sources, although Linnaeus didn't include C. ruffus in either the 1758 or the 1766 edition of his Systema Naturae—instead, its first post-Linnaean description was written by Laurenti in 1768. Compared with other Cylindrophis, C. ruffus has a much larger distribution than any other species of Asian pipesnake. It's one of those species that is really a species complex—a group of closely related species that are very similar in appearance, to the point that the boundaries between them are often unclear. Other well-known examples include African House Snakes (Boaedon fuliginosus, formerly Lamprophis fuliginosus) and American Milksnakes (Lampropeltis triangulum). Often unusual populations of these species are described as separate species, but without extensive rangewide sampling it's easy to miss more subtle, clinal variation, especially when that variation is genetic rather than morphological. A recent revision of milksnakes split this wide-ranging species into several, and researchers have been working on African House Snakes as well. But no one has really examined Red-tailed Pipesnakes. Last year, a group of European and Indonesian researchers examined a large number of Cylindrophis museum specimens and discovered several specimens which did not fit any recognized species. But many of these specimens are old and some of their locations are uncertain. We don't have a lot of molecular data, and we have no specimens at all from many areas. And, no one has yet carried out a totally comprehensive review of the species complex (which really should encompass the entire genus, since the milksnake researchers found that some "milksnakes" were actually more closely related to mountain kingsnakes than they were to other milksnakes).

Cylindrophis ruffus raising its tail "flag"

Despite its re-description in 2015, Cylindrophis ruffus is still a species complex that suffers from a lot of complexity. Its morphology is highly variable. Its geographic range limits are unsettled. There is no type specimen. The original type locality (“Surinami”) is a hemisphere away, obviously an error, which complicates decisions about which populations of C. ruffus should get to keep that name and which should change. The 2015 paper, as the authors of this month's paper delicately put it, "contain[s] some inaccuracies, including descriptive errors, which unfortunately increase the complexity of an already intricate taxonomic situation". The researchers state that they are currently undertaking the kind of comprehensive review that I called for above, but that in the process they discovered a morphologically distinct population from central Java, which they describe as Cylindrophis subocularis in this paper. But the real value of this paper, in my mind, is the step-by-step description of the history of this snake, starting with its first depiction in 1735 and continuing to present day. I'll leave the gory details for those who are really interested (the full-text is available here), but suffice it to say that the story of Cylindrophis ruffus is much more interesting than I ever knew (it took almost 100 years to get the geography right), and far from over.

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1 Granted, it was a photo of a preserved specimen.^↩

ACKNOWLEDGMENTS

Thanks to M. A. Muin, Nigel Swales and Marcus Meissner for the use of their photos.

REFERENCES

Amarasinghe, A. A. T., P. D. Campbell, J. Hallermann, I. Sidik, J. Supriatna, and I. Ineich. 2015. Two new species of the genus Cylindrophis Wagler, 1828 (Squamata: Cylindrophiidae) from Southeast Asia. Amphibian and Reptile Conservation 9:34-51 <link>

Gower, D. J., E. O. Z. Wade, S. Spawls, W. Böhme, E. R. Buechley, D. Sykes, and T. J. Colston. 2016. A new large species of Bitis Gray, 1842 (Serpentes: Viperidae) from the Bale Mountains of Ethiopia. Zootaxa 4093:41-63 <link>

Kieckbusch, M., S. Mecke, L. Hartmann, L. Ehrmantraut, M. O’Shea, and H. Kaiser. 2016. An inconspicuous, conspicuous new species of Asian pipesnake, genus Cylindrophis (Reptilia: Squamata: Cylindrophiidae), from the south coast of Jawa Tengah, Java, Indonesia, and an overview of the tangled taxonomic history of C. ruffus (Laurenti, 1768). Zootaxa 4093:1-25 <link>

Malonza, P. K., A. M. Bauer, and J. M. Ngwava. 2016. A new species of Letheobia (Serpentes: Typhlopidae) from central Kenya. Zootaxa 4093:143-150 <link>

Scheuchzer, J. J. 1735. Physica Sacra Iconibus Anaeis Illustrata, Procurante & Sumtus Suppeditante. Tomus IV. Augustae Vindelicorum et Ulmae, Ulm <link>

Seba, A. 1734-1765. Locupletissimi rerum naturalium thesauri accurata descriptio, et iconibus artificiosissimis expressio, per universam physices historiam :opus, cui, in hoc rerum genere, nullum par exstitit. Apud Janssonio-Waesbergios & J. Wetstenium & Gul. Smith, Amstelaedami <link>

Life is Short, but Snakes are Long by Andrew M. Durso is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Book Review: Bushmaster by Dan Eatherley

Click here to read this post in Spanish

Haga clic aquí para leer este artículo en español

Bushmaster (Lachesis muta) from Peru

Lachesis is the name of one of the three Greek Moirai or Fates, sister-deities who determined the destiny of every human life by spinning each life as a thread on a loom. Her role in the process was to determine the length of a mortal's life, and so she is appropriately immortalized¹ in modern biology in the genus name of Bushmasters, huge Latin American pitvipers that occasionally play the same role and are herpetologically mythical in their own right. Her sisters, Clotho (who spun the threads of life) and Atropos (who did the actual thread-cutting), are similarly honored in the Latin name of vipers of the genus Atropoides and in Clotho, an old synonym for some members of the African viper genus Bitis.

Ditmars filming the Bushmaster "Lecky" at the Bronx Zoo in 1934
©WCS. Courtesy of the WCS Archives

If you're interested in Bushmasters and herpetological history, check out Dan Eatherley's new book, "Bushmaster: Raymond Ditmars and the Hunt for the World's Largest Viper", which chronicles the life and times of the Bronx Zoo's first reptile curator and one of America's first and most successful popular herpetological writers. Ditmars authored 24 books, >200 articles, and pioneered nature films in an era when video technology was still in its infancy. Eighty years ago, he was a household name in New York, enjoying a celebrity attained by few herpetologists. President Theodore Roosevelt praised Ditmars's The Reptile Book and invited him to the White House. One of the reasons for his popularity was his "obsession" with keeping large, exotic, sexy, venomous snakes—such as Bushmasters—in captivity, an endeavor on which the press regularly reported. Ditmars was reporter for New York Times when he was young, and the paper published 12-15 stories a year on his exploits between 1899 and 1942. Such was the popularity drummed up for snakes that, when a short-lived Bushmaster named "Lecky" was exhibited at the Bronx Zoo in 1934, it was credited with attracting an estimated 100,000 additional guests at the zoo and a 60% increase in visitors at the nearby American Museum of Natural History’s reptile hall.

The first photograph of a female Bushmaster guarding her eggs,
taken by C.S. Rogers in Trinidad, was published in Ditmars (1910),
and subsequently as a postcard sold at the Bronx Zoo.
The snake was a captive in the possession of R.R. Mole.

Bushmasters are unique among New World vipers, with the possible exception of the rare Bothrops colombianus, in laying eggs rather than giving birth to live young. Because they guard their eggs, a phenomenon that Ditmars and his correspondent R.R. Mole first described, they may offer insight into the complex evolution of parental care in pitvipers. In Ditmars's time, there was a single, widespread species of bushmaster, with four subspecies separated by tropical mountain ranges; we now recognize those four subspecies as species on the basis of morphological, behavioral, and molecular differences. Bushmasters are also the only pitvipers where the venom of juveniles appears to lack the chemical potency of adults, at least towards mammals. Many vipers feed on amphibians or other reptiles when they are young and switch to mammals as they grow up², which might explain this observation. Bushmasters are the world's longest vipers³ (Gaboon Vipers exceed them in weight) and the longest venomous snakes in the Americas (King Cobras exceed them in length).

Ditmars wears a snake fang tie pin
on the book's cover

Eatherley's book is well-researched and accurate. I found it to be an exciting read with an excellent historical perspective. My biggest criticism was that it was a little sensational at times, as are most popular accounts dealing with venomous snakes. I particularly enjoyed the author's description of his experiences meeting up with some New York City herpers to seek Gartersnakes (Thamnophis sirtalis), Brownsnakes (Storeria dekayi), and other snakes that could still be found in the northern part of Central Park in the 1880s, when Ditmars was cutting his herpetological teeth. I was also interested to learn that Ditmars supplied snake venom to early antivenom producers and set a precedent, still in place today, of zoos stocking exotic snake antivenoms for the dual purpose of protecting their keepers and providing them to the medical community when bites from exotic species occur elsewhere.

In his writing, Ditmars often portrayed Bushmasters as aggressive, in contrast to many other herpetologists who have described their manner as relatively gentle, even timid. In reality, they are, like most venomous snakes, cowards first, then bluffers, and lastly warriors, and their large size has earned them a reputation as formidable warriors as well as a prominent position in folklore throughout Latin America⁴. Their mystique and biology effectively drive Eatherley's book, only the second biography of Ditmars ever written (the first, by Laura Newbold Wood, was written for children and published in 1944, just two years after Ditmars's death). Throughout the book, Eatherley goes from stating that negative responses towards reptiles are “of course, the norm for most of us” (p. 11) to tracing a rapid path from ecstasy to palpable disappointment, familiar to any snake enthusiast, when informed during his search for a wild Bushmaster in Trinidad that a nearby farmer has found one, but killed it (p. 255). I think that Ditmars would be pleased with his abiding influence, nearly 75 years after his death, in inspiring passion for and love of snakes.

You can read two other reviews of Eatherley's book, published last month in Copeia and Herpetological Review.

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1 I suppose she was already immortal, since she's a Greek Goddess.^↩

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2 Strangely, bushmasters seem to be one of the only vipers where this shift is not well-documented. Collecting data on young snakes is hard, and the venom study found that venom chemistry became more adult-like after just one year, so perhaps we've just missed the shift. Another hypothesis is that bushmasters tend to hold onto their prey after striking it, unlike other vipers which strike, release, and relocate, so perhaps the rapid immobilizing venom components have been replaced by a mechanical means of immobilization.^↩

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3 Regarding their maximum length, Campbell & Lamar's authoritative reference on venomous reptiles of the western hemisphere says: "Documented reports of measured specimens are scarce, however, and the maximum length has been the subject of some hyperbole. Hoge and Lancini (1962) claimed 4.5 m, Abalos (1977) claimed 3.5 m, Ditmars (1937) mentioned specimens of 11 feet (3.35 m) but apparently never saw one exceeding 3m, Bellairs (1969) gave the maximum length as between 3.05 and 3.36m, Dunn (1951) gave the maximum length as 14 feet (4.27 m), and Mertens (1960) listed 13 feet (3.96 m) as the maximum size. Sandner-Montilla (1994) claimed a record of 5.28 m for a Venezuelan specimen of L. muta (with 6-cm fangs!), but such records must be placed in the same realm as 20-m anacondas and other legendary monsters.", and concludes "The great majority of adult specimens of all species of Lachesis measure less than 2.5 m, and 3.5 m is likely near the maximum size."^↩

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4 Bushmasters play other roles in human culture as well—as food. Bora and Yagua Indians in eastern Peru consider them a delicacy. They are certainly one of the few snakes large enough to make a filling meal for a family.^↩

ACKNOWLEDGMENTS

Thanks to Dan Eatherley and Arcade Publishing for producing such a wonderful book, of which they kindly provided me a copy, to Drew Foster for sharing an advance copy of his review of this book for Copeia, to Marisa Ishimatsu and the Wildlife Conservation Society for the use of their photographs, and to Harry Greene for shedding a little more light on the diets of juvenile bushmasters.

REFERENCES

Adler, K. 1989. Contributions to the History of Herpetology. Volume 1. Society for the Study of Amphibians and Reptiles, Oxford, Ohio <link>

Campbell, J. A., and W. W. Lamar. 2004. The Venomous Reptiles of the Western Hemisphere (2 Vol.). Cornell University Press, Ithaca, New York <link>

Ditmars, R. L. 1910. Reptiles of the World : Tortoises and Turtles, Crocodilians, Lizards, and Snakes of the Eastern and Western Hemispheres. Macmillan Co., New York <link>

Gutiérrez, J., C. Avila, Z. Camacho, and B. Lomonte. 1990. Ontogenetic changes in the venom of the snake Lachesis muta stenophrys (bushmaster) from Costa Rica. Toxicon 28:419-426 <link>

Eatherley, D. 2015. Bushmaster: Raymond Ditmars and the Hunt for the World's Largest Viper. Arcade Publishing, New York, New York <link>

Foster, C. D. 2015. Bushmaster: Raymond Ditmars and the Hunt for the World’s Largest Viper [book review]. Copeia 103:1107-1109 <link>

Novotny, R. J. 2015. Bushmaster: Raymond Ditmars and the Hunt for the World's Largest Viper [book review]. Herpetological Review 46:657-659 <link>

Wood, L. N. 1944. Raymond L. Ditmars: His Exciting Career With Reptiles, Animals and Insects. The Junior Literary Guild and Julian Messner, Inc., New York <link>

Zamudio, K. R., and H. W. Greene. 1997. Phylogeography of the bushmaster (Lachesis muta: Viperidae): implications for neotropical biogeography, systematics, and conservation. Biological Journal of the Linnean Society 62:421-442 <link>

Life is Short, but Snakes are Long by Andrew M. Durso is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Do snakes sleep?

Click here to read this article in Spanish.
Haga clic aquí para leer este artículo en español.

Do snakes sleep? Do they dream? These may seem like obvious questions, especially since almost every species of mammal, bird, reptile, amphibian, fish, and invertebrate studied has been found to exhibit some kind of resting phase. But sleep is hard to study in snakes, at least in part because they seem never to close their eyes. Consequently, there is shockingly little research on sleep in snakes. A Google Scholar search for the terms "snake+sleep" returns papers about venomous snakebites to sleeping victims, sleepwalkers dreaming about snakes, and papers by Stanford geophysicist Norman H. Sleep on the geology of the Snake River in Idaho. But, despite the dearth of research, I promise this post won't be too much of a snooze...

Human EEG "brainwaves"

Sleep is a behavior that involves an immobile posture, decreased responsiveness to arousing stimuli such as noise and light, and rapid reversibility (the ability to quickly "wake up", as distinct from hibernation or a comatose state). The physiological criterion most frequently used to define sleep is the slowing down of "brain-waves" on an EEG. An EEG (electroencephalogram) measures electrical activity in your brain, which is caused by your brain cells talking to one another. Brain activity, which happens even during sleep, appears as wavy lines on an EEG recording, hence brain 'waves'. When mammals and birds are sleeping, they exhibit two alternating patterns of EEG activity: 1) slow-wave sleep (SWS, also called synchronized, quiet, or non-REM sleep), which is characterized by high amplitude (75-400 μV), low frequency (0.5-4 Hz) EEG waves, and 2) "paradoxical" sleep (PS, also called desynchronized, active, or REM sleep), which is characterized by low voltage (5-10 μV), high frequency (13-30 Hz) EEG waves that are physiologically more like those in awake animals (hence the name "paradoxical"). In humans and cats, paradoxical sleep is associated with rapid-eye movement (REM, measured by electro-oculography or EOG), complete muscle relaxation (measured by electromyography or EMG), muscle twitching, irregular breathing/heartbeat, and, in humans at least, with dreaming.

Lizards wearing EEG-recording equipment while awake and asleep
From Flanigan 1973

Although sleeping patterns are enormously variable across the animal kingdom, most mammals and birds tested exhibit both SWS and PS, or variations on that theme. In some basal mammals and birds (echidnas, platypus, ostriches), eye movement and relaxed muscle tone are associated with both quiet and active sleep. Periods of rest or quiescence associated with EEG changes similar to those seen in mammalian sleep are clearly present in turtles and in crocodilians, but EEG data suggest that these animals do not exhibit REM sleep. Some experiments have found REM-like sleep in lizards, whereas others have not. In experiments where lizards, turtles, and crocodilians were subjected to continuous arousal for 24-48 hours, they appeared to get tired, sleeping more afterwards and producing more high-voltage EEG spikes. Tortoises given the drug atropine, derived from the mandrake plant and used to produce deep sleep in humans since at least the fourth century B.C.E., also produced more spikes, suggesting that EEG spikes are in fact analogous signs of quiet sleep in reptiles and mammals. Interpreting EEG data is complicated because SWS waves differ between mammals and reptiles, perhaps because reptile and mammal brains differ in structure, particularly with respect to the neocortex, the source of these waves in mammals. Furthermore, some reptiles sometimes seem to exhibit sleep-like brain activity when they are awake, perhaps because ectotherms basically fall asleep when they get cold.

Waking (top) and sleeping (bottom) python EEG
and EMG waves. From Peyrethon & Dusan-Peyrethon 1969

The single study of a snake was done by French comparative sleep researchers J. Peyrethon and D. Dusan-Peyrethon (I could not find their full first names), who also studied sleep in fish, caimans, cats, and mice in the 1960s at the Laboratoire de Médecine Expérimentale in Lyon. They used EEG to monitor the brainwaves of a four-foot African Rock Python (Python sebae) over two days. They reported that sleep-like brain waves were produced almost 16 hours a day, increasing to over 20 hours following feeding, and that these brainwaves corresponded with slower breathing and heart rate, some muscle relaxation, and perhaps a lowered behavioral response threshold. They did not see any evidence for active sleep in the EEG. As far as I can tell, this is the only study ever conducted on sleep in a snake.

Snakes do have circadian rhythms, and many snakes are active only at particular times of day. Racers (Coluber), hog-nosed snakes (Heterodon), patch-nosed snakes (Salvadora), and sipos (Chironius) are strictly diurnal, whereas aptly-named nightsnakes (Hypsiglena), broad-headed snakes (Hoplocephalus), and kraits (Bungarus) are strictly nocturnal. But many snakes do not fit nicely into these categories. Good examples include ratsnakes (Pantherophis) and many vipers, but many other snakes may be active at any time of the day or night, depending on the time of year, so it's hard to predict when or for how long they might be expected to sleep. You often observe snakes exhibiting sleep-like behavior, sitting in one spot for hours, days, or even weeks at a time, like the Puff Adder (Bitis arietans) in the video at left. But the thing is, that snake is actually foraging. A viper might sit motionless for many days, such a long time that if a mammal exhibited that same behavior, we might think it was sick or dead! But in fact this is how many snakes forage for prey, hyper-alert to their immediate surroundings, ready to ambush, strike, and envenomate small animals that stray too close. Do they sleep when they are waiting, or are they awake the entire time? Radio-telemetry studies of bushmasters (Lachesis muta) in the wild suggest that they might have strict cycles of attentiveness, "awesomely alert during darkness and almost as if drugged by day", with relatively abrupt transitions each way. On the other hand, many marine mammals and migratory birds do not seem to sleep for long periods of time without suffering any obvious consequences. When engaged in constant activity, these animals close one eye and sleep one half of their brain at a time. Other animals, including perhaps some lizards, sleep one hemisphere at a time in contexts of high predation risk. Might snakes that use sit-and-wait foraging strategies do something similar?

I photographed this Sonoran Lyresnake (Trimorphodon lambda)
during the day, but it was found at night. Their skinny slit-like
pupils enhance their night vision, making distant
objects sharper by increasing the depth of field,
like using a small aperture on a camera lens.
If lyresnakes sleep, it's probably during the day.

How would a researcher tell if a snake was sleeping? Snakes never close their eyes. Or, more accurately, their eyelids are always closed, but they are covered by clear scales. Either in the wild or in captivity, observations of snakes seeming to "wake up" (implying that they were sleeping) are rare: motionless snakes rarely twitch, and other signs of PS are either normal for snakes (such as irregular breathing/heartbeat) or anatomically impossible (REM). You could imagine a series of experiments where an experimenter used EEG and high-speed infrared videography to record the brainwaves and behavioral responses of snakes to arousing stimuli. What stimuli to use is an open question, since snakes don't necessarily respond to bright lights or loud noises even when they're awake. Because snakes inhabit a primarily chemosensory world, it might be possible to wake one up using a smell. The human experience would suggest that the onset of chemosensory signals is inherently too gradual to really be surprising, but this might or might not be true for snakes. What about the infrared sense of some snakes? Could a bright infrared light wake them up? Can snakes see when they're asleep? What would that even be like? Only further studies will tell for sure.

So here's what we know: snakes probably do sleep, perhaps most of the time, but we don't really know when, for how long, how deeply, or whether or not they have paradoxical sleep, including dreaming. Sleep patterns are probably quite diverse across the >3500 species, of which only one has been examined. Many snakes do yawn, but this has been interpreted either as a means to gather chemical cues or to reposition musculoskeletal elements, in contrast with the hypothesized functions of yawning in humans (possibly regulating brain temperature, causing increases in blood pressure, blood oxygen, and/or heart rate in order to improve motor function and alertness, or as a social cue). Sleep is such a basic element of human biology, so if you ask me, the subject of sleep in snakes, and broader questions about the diversity, evolution, and function of sleep across the animal kingdom, should be keeping researchers awake at night.

ACKNOWLEDGMENTS

Thanks to Kendal Morris for suggesting this question, and to Harry Greene, David Cundall, and Gordon Burghardt for sharing their observations.

REFERENCES

Ayala-Guerrero, F., & Huitrón-Reséndiz, S. 1991. Sleep patterns in the lizard Ctenosaura pectinata. Physiology & Behavior 49:1305-1307 <link>

Bauchot, R. 1984. The phylogeny of sleep in vertebrates [birds, reptiles, amphibians, fish]. Annee Biologique (France) 23:367-392 <link>

Brischoux, F., Pizzatto, L., & Shine, R. 2010. Insights into the adaptive significance of vertical pupil shape in snakes. Journal of Evolutionary Biology 23:1878-1885 <link>

Campbell, S. S., & Tobler, I. 1984. Animal sleep: a review of sleep duration across phylogeny. Neuroscience & Biobehavioral Reviews 8:269-300 <link>

De Vera, L., González, J., & Rial, R. V. 1994. Reptilian waking EEG: slow waves, spindles and evoked potentials. Electroencephalography and Clinical Neurophysiology 90:298-303 <link>

Flanigan, W. F. 1973. Sleep and wakefulness in iguanid lizards, Ctenosaura pectinata and Iguana iguana. Brain, Behavior, and Evolution 8:417-436 <link>
 

Greene, H. W., & Santana, M. 1983. Field studies of hunting behavior by bushmasters. Estudios de campo del comportamiento de caza por parte de las cascabelas mudas. American Zoologist 23:897 <link>.

Hartse, K.M. and A. Rechtschaffen. 1974. Effect of atropine sulfate on the sleep-related EEG spike activity of the tortoise, Geochelone carbonaria. Brain, Behavior, and Evolution 9:81-94 <link>

Libourel, P. A., & Herrel, A. 2015. Sleep in amphibians and reptiles: a review and a preliminary analysis of evolutionary patterns. Biological Reviews <link>

Peyrethon, J., & Dusan-Peyrethon, D. 1969. Etude polygraphique du cycle veille-sommeil chez trois genres de reptiles. CR Soc Biol (Paris) 163:181-186 <not available online>

Rattenborg, N. C. 2006. Do birds sleep in flight? Naturwissenschaften 93: 413-425 <link>

Roe, J. H., Hopkins, W. A., Snodgrass, J. W., & Congdon, J. D. 2004. The influence of circadian rhythms on pre-and post-prandial metabolism in the snake Lamprophis fuliginosus. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 139:159-168 <link>

Siegel, J. M. 2008. Do all animals sleep? Trends in Neurosciences 31: 208-213 <link>

Siegel, J. M., Manger, P. R., Nienhuis, R., Fahringer, H. M., Shalita, T., & Pettigrew, J. D. 1999. Sleep in the platypus. Neuroscience 91: 391-400 <link>

Tauber, E.S., J. Rojas-Ramirez, and R. Hernandez-Peon. 1968. Electrophysiological and behavioral correlates of wakefulness and sleep in the lizard (Ctenosaura pectinata). Electroencephalography and Clinical Neurophysiology 24:424–443 <link>

Life is Short, but Snakes are Long by Andrew M. Durso is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.