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An important note on the use of the terms, “venom” and “venomous” for non-front-fanged colubroid1 snakes and other squamate reptiles www.toxinology.com

The following encapsulates the issues arising from the paper of Fry et al (2012) The structural and functional diversification of the Toxicofera reptile venom system, and the replies to that paper published in Toxicon (click on the title to download a copy):

The traditional synthesized consensus definition of venom is: “a complex substance produced in a specialized gland and delivered by an associated specialized apparatus that is deleterious to other organisms in a given dosage and is actively used in the subjugation and/or digestion of prey and/or in defense” (Minton, 1974; Minton and Minton, 1980; Russell, 1983; Mebs, 2002). According to this definition biological function, that is how it is used, is a crucial defining factor. This integral component of the traditional perception of venom is commonly confused with medical significance in the popular, and occasionally, in the medical and even scientific literature. In this consensus, the medical effects of snake venoms are a circumstantial result of the intersection of humans with snakes that produce venoms, which coincidentally have a medically significant effect on a human victim. Venomous snakes evolved long before humans and thus their venoms are directed at increasing their likelihood of survival, their fitness, within their hostile and challenging environment, and not for the explicit purpose of being used against humans. Therefore, the medical effects of snake venoms should not be used as a criterion to define what is “venomous” and what is not. Most previous authors have emphasized the immobilization/procurement of prey as the primary defining criterion with defensive functions against natural predators of secondary importance. The digestive functions of snake venoms are likely of earlier origin (Minton, 1971; Chippaux, 2006).

Since the early 19th century there has been strong interest in the toxic nature of “colubrid” (=non-front-fanged colubroids) oral products, as well as consideration of whether these were venoms, and thereby whether these snakes should be considered “venomous”.  Detection or isolation of proteins/toxins commonly found in front-fanged snake venoms from some non-front-fanged colubroid oral products (“Duvernoy’s secretions”, or “venoms”) have been reported since the late 1970’s. Throughout the 20th century, there has been confusion regarding how and when to apply the term, “venom”, or “venomous”, to various non-front-fanged colubroid snakes. As a specific example, Cowles (1941) reported the effects of bites inflicted by the spotted or coastal night snake (Hypsiglena ochrorhynchus) on a variety of lizards, and noted that the effects ranged from slight discoloration to death. Goodman (1953) reported delayed (about 2 hr) death of sagebrush lizard (Sceloporus graciosus) after being “chewed on” by a Hypsiglena spp. However, Dundee (1950) reported that a Texas night snake (H. torquata texana=H. ochrorhynchus texana Mulcahy, 2008) briefly seized a worm snake (Leptotyphlops spp.) without any observed effect. Therefore, some authors subsequently variably described Hypsiglena spp. as “venomous”, “non-venomous”, “mildly venomous”, or, with “saliva” of a “venomous nature”. There are similarly inconsistent descriptions in the literature of a significant number of common non-front-fanged colubroid snakes.

Some trained observers have reported unambiguous use of non-front-fanged colubroid oral products that clearly is consistent with the traditional consensus definition of “venom” in that these were actively used in order to subdue prey. Some of these include: the green vine snake (Oxybelis fulgidus), the ringneck snake (Diadophis punctatus), the Puerto Rican racer (Alsophis portoricensis=Borikenophis portoricensis Hedges et al., 2009) and the mangrove snake (Boiga dendrophila) (see Weinstein et al., 2011, for a review of these reports). However, there are other species for which there is no evidence of the active, consistent use of oral products in prey capture and/or self-defense, regardless of their experimental toxicity and demonstrated content of toxins common in snake venoms. Some of these species include garter and ribbon snakes (Thamnophis spp.), hognose snakes (Heterodon spp.) and false water cobras (Hydrodynastes gigas). There are a very large number of non-front-fanged colubroid taxa, in fact the majority of the approximately 2,350 species, that have oral products with unknown properties and function. Therefore, these may or may not produce “venoms”, and it is scientifically inaccurate to assign them the title of “venomous” without further information.

Recently, some of the genes and/or their transcripts encoding several classes of the aforementioned toxins and other biologically active venom components have been detected in some non-front-fanged colubroid snakes, as well as in several lizard oral products (e,g. Fry et al., 2006, 2009, 2012). This has stimulated renewed attention to the origin of squamate reptile venoms, and the applicability of the traditional interpretation of “venom” and the “venomous condition”. Although the presence of these biologically active proteins and toxins provide fertile ground for research regarding their origin, again, their basic biological functions in many species are unclear. Therefore, it is not currently ascertained if these substances are a consequence of pre-adaptation (recruitment of previously existing proteins for a later role in the organism’s natural history), or if they provide a specific selective advantage in survival. Speculation about possible roles of these oral products must be investigated with caution as premature assignment of the indelible term, “venom”, implies active functional use in prey subjugation, digestion and/or self-defense and carries secondary medical as well as legal implications. Until these data are reproduced by independent investigations and further information about their function(s) is procured, it is premature and misleading to refer to them as “venoms”. For example, data that suggest hypotensive effects of oral products from lizards such as Varanus varius (Australian lace monitor) must be tempered with early research that showed similar potent vasopressor and/or vascular permeability effects of feline and human saliva (Gibbs, 1935; Levy and Appleton, 1942). Also, human saliva is toxic and contains multiple classes of ≥309 proteins (including toxins) that can be found in venoms (Bonilla et al., 1971; Hu et al., 2005; Weinstein et al., 2010). Thus, until there is achieved a more comprehensive scientific as well as biomedical understanding of these interesting saurian oral products, their biological roles and medical significance remain unestablished.

It is also essential to comprehend that the term, “non-venomous”, is used here to indicate those snakes that do not have venom, and also for those that produce oral secretions that may contain identifiable toxins common to some snake venoms, but that do not have a reasonably evidenced role in the survival of the snake; per capture of natural prey and/or self-defense against natural predators. Thus, some “non-venomous” species may be capable of rarely inflicting medically significant bites on humans, and their oral products, secretions, Duvernoy’s secretions, etc., should not be considered “harmless” on the basis of a different terminology. This means that biologically, sensu stricto, the word “venom” should not be interpreted as necessarily medically dangerous, and “toxic oral secretion, or Duvernoy’s secretion, should conversely not be interpreted as harmless by default. The medical significance of a given non-front-fanged colubroid snake and a significant number of little known small fossorial front-fanged species is determined in a case-by-case basis, and this is complicated due to the paucity of information regarding the involvement of the majority of these snakes in bites.

Finally, it is important to note that although in our replies there is provisional adherence to the traditional consensus definition of “venom” and “venomous”, there is absolutely no rigid resistance to a future change in the consensus definition as further information may indicate the need for modification of the defining criteria. Due to the mixed and, on occasion, inconsistent use of these terms in the herpetological, toxinological and medical literature over the last 50 or so years, a formal change should include an interdisciplinary consensus among the aforementioned communities that includes evolutionary, behavioural, biochemical, morphological and medical perspectives.

1Non-front-fanged colubroids refers to all snakes previously called “rear-fanged colubrids”; “opisthoglyphous colubrids”, or “aglyphous colubrids”. This included all of the artificial assemblage, the family Colubridae, which is undergoing major taxonomic review. A significant number of the former members of this family have already been re-assigned to different families or sub-families.

References

Bonilla, CA, Fiero, MK, Seifert, W. 1971. Comparative biochemistry and pharmacology of salivary glands. 1. Electrophoretic analysis of the proteins in the secretions from human parotid and reptilian (Duvernoy's) glands. 1. Chromatogr. 56: 368-372.

Chippaux, JP. 2006. Snake Venoms and Envenomation. Krieger Publishing Company, Melbourne.

Cowles, RB. 1941. Evidence of venom in Hypsiglena ochrorhynchus. Copeia 1941(1); 4-5.

Dundee, HA. 1950. Additional records of Hypsiglena from Oklahoma, with notes on the behaviour and the eggs. Herpetologica 6, 28-30.

Fry, BG, Vidal, N, Norman, IA, Vonk, FI, Scheib, H, Ramjan, SFR, Kuruppu, Fung, SK, Hedges, SB, Richardson, MK, Hodgson, WC, Ignjatovic, V, Summerhayes, R, Kochva, E. 2006. Early evolution of the venom system in lizards and snakes. Nature 439:584-88.

Fry, BG, Wroe, S, Teeuwisse, W, van Osch, MJ, Moreno, K, Ingle, J, McHenry, C, Ferrara, T, Clausen, P, Scheib, H, Winter, KL, Greisman, L, Roelants, K, van der Weerd, L, Clemente, CJ, Giannakis, E, Hodgson, WC, Luz, S, Martelli, P, Krishnasamy, K, Kochva, E, Kwok, HF, Scanlon, D, Karas, J, Citron, DM, Goldstein, EJ, McNaughtan, JE, Norman, JA. 2009. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus. Proc. Natl. Acad. Sci. USA. 106: 8969-8974.

Fry, BG, Casewell, NR, Wüster, W, Vidal, N, Young, B, Jackson, NWJ. 2012 (in press). The structural and functional diversification of the Toxicofera reptile venom system. Toxicon (2012), doi:10.1016/j.toxicon.2012.02.013

Gibbs, OS. 1935. On the alleged occurrence of acetylcholine in the saliva. J. Physiol. 84: 33-40.

Goodman, JD. 1953. Further evidence of the venomous nature of the saliva of Hypsiglena ochrorhyncha. Herpetologica 9, 174.

Hedges, SB, Couloux, A, Vidal, N. 2009. Molecular phylogeny, classification and biogeography of West Indian racer snakes of the tribe Alsophiini (Squamata, Dipsadidae, Xenodontinae). Zootaxa 2067, 1-28.

Hu, S, Xie, Y, Ramachandran, P, Ogorzalek, Loo, RR, Li, Y, Loo, JA and Wong, DT. 2005. Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry. Proteomics 5: 1714-1728.

Levy, BM, Appleton, JLT. 1942. Effect of saliva on capillary permeability. J. Dent. Res. 21: 505-508.

Mebs, D. 2002. Venomous and Poisonous Animals. CRC Press, Boca Raton, FL.

Minton, SA (Ed). 1971. Snake Venoms and Envenomation. Dekker, NY.

Minton, SA. 1974. Venom Diseases. Charles C. Thomas., Springfield, Illinois.

Minton, SA, Minton, MR. 1980. Venomous Reptiles. Scribners, NY.

Mulcahy, DG. 2008. Phylogeography and species boundaries of the Western North American nightsnake (Hypsiglena torquata): revisiting the species concept. Mol. Phylogen. Evol. 46, 1095-1115.

Russell, FE. 1983. Snake Venom Poisoning. Scholium International. Great Neck, NY.

Weinstein, SA, Smith, TL, Kardong, KV. 2010. Reptile venom glands: Form, function, and future. Pp. 65-91. In: CRC Handbook of Reptile Venoms and Toxins, Mackessy, SP (ed.), CRC, Taylor Francis, Boca Raton, pp. 521.

Weinstein, SA, Warrell, DA, White, J, Keyler, DE. 2011. “Venomous Bites From Non-Venomous Snakes: A Critical Analysis of Risk and Management of “Colubrid” Snake Bites”. Elsevier Science, Oxford, pp. 364.

Weinstein, SA, Keyler, DE, White, J. 2012 (in press). Replies to Fry et al. (Toxicon 2012 XX, 1–15). Part A. Analyses of squamate reptile oral glands and their products: A call for caution in formal assignment of terminology designating biological function, Toxicon (2012), 10.1016/j.toxicon.2012.05.006

Kardong, KV. Part B. 2012 (in press) Replies to Fry et al. (Toxicon 2012 XX, 1–15). Part B. Properties and biological roles of squamate oral products: The “venomous lifestyle” and preadaptation, Toxicon (2012), http://dx.doi.org/10.1016/ j.toxicon.2012.06.001