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)
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:
The science: part II (how cobras got their flesh-eating venoms)
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?
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 science: part I (puff adders)
A puff adder (Bitis arietans) |
This research matters because venomous snakes and their prey are in constant evolutionary arms races, leading to:
- a mosaic of new biochemical compounds that are often useful in treating disease
- a mosaic of new biochemical compounds that can make venomous snakebite really hard to treat
The science: part II (how cobras got their flesh-eating venoms)
A Mozambique spitting cobra (Naja mossambica) spitting its venom |
Toxicity of snake venom to human cells grown in culture. Warm colors indicate higher toxicity. From Panagides et al. 2017 |
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 |
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! |
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.
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.↩
2 Recent update here; you can write the governor of Massachusetts here.↩
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>
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.
3 comments:
I wanted to let you know that I absolutely love this blog and have read a ton of your posts since I discovered it a few weeks ago. As a kid, I wanted to become a herpetologist for a very long time. I ended up becoming a psychological scientist instead, but reading your posts has helped me rediscover my love of snakes (well, that and buying my ball python, Smaug).
Cheers, and I sincerely hope you continue to keep up this blog -- I know from experience that writing these posts must be a ton of work!
Thank you very much Patrick. You're correct that it's a lot of work; I really enjoy writing it so I'm really glad to hear from people who really enjoy reading it. I'm actually planning a post on fear of snakes that should have several psychological aspects of interest to you.
That's great to hear! I'll certainly be following along. :)
Post a Comment