toxins Communication The Curious Case of the “Neurotoxic Skink”: Scientific Literature Points to the Absence of Venom in Scincidae Kartik Sunagar 1,* and Siju V Abraham 2 1 Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, Karnataka, India 2 Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute, Thrissur 680005, Kerala, India; [email protected] * Correspondence: [email protected] Abstract: In contrast to the clearly documented evolution of venom in many animal lineages, the origin of reptilian venom is highly debated. Historically, venom has been theorised to have evolved independently in snakes and lizards. However, some of the recent works have argued for the common origin of venom in “Toxicofera” reptiles, which include the order Serpentes (all snakes), and Anguimorpha and Iguania lizards. Nevertheless, in both these contrasting hypotheses, the lizards of the family Scincidae are considered to be harmless and devoid of toxic venoms. Interestingly, an unusual clinical case claiming neurotoxic envenoming by a scincid lizard was recently reported in Southern India. Considering its potentially significant medicolegal, conservation and evolutionary implications, we have summarised the scientific evidence that questions the validity of this clinical report. We argue that the symptoms documented in the patient are likely to have resulted from krait envenomation, which is far too frequent in these regions. Keywords: venom evolution; the origin of reptilian venom; neurotoxic venoms in skinks Key Contribution: While many lineages of snakes and lizards are widely accepted to be venomous, Citation: Sunagar, K.; Abraham, S.V. the presence of toxic saliva in skinks (Family: Scincidae) is scientifically unsupported. Despite this, a The Curious Case of the “Neurotoxic clinical case claiming neurotoxic envenoming by a scincid lizard was recently reported in Southern Skink”: Scientific Literature Points to India. However, our understanding of venom evolution, clinical signs and symptoms of the patient, the Absence of Venom in Scincidae. and the epidemiology of the region, contests the validity of this case report. Toxins 2021, 13, 114. https://doi.org/ 10.3390/toxins13020114 Received: 27 December 2020 1. Introduction Accepted: 1 February 2021 Published: 3 February 2021 Traditionally, an anthropocentric interpretation of venoms has led to the consideration of only animals capable of inflicting clinically severe symptoms in humans as “venomous”, whereas the ecological roles of these toxic secretions have been largely neglected. Over the Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in past few decades, however, investigations into the impact of ecology and environment in published maps and institutional affil- shaping animal venoms have gained momentum [1]. Several studies have now demon- iations. strated the roles of diet, ontogeny, predator pressure, intraspecific competition, geographic distribution, and climatic conditions in shaping animal venoms [2–6]. For instance, a relatively reduced or complete loss of toxicity towards mammals has been shown in certain snakes that chiefly feed on non-mammalian prey systems [6–8], making them ineffective or relatively less effective against humans. The modern definition, therefore, defines venom Copyright: © 2021 by the authors. as a specialised form of poison that is actively injected to facilitate the quotidian functions Licensee MDPI, Basel, Switzerland. This article is an open access article of the venomous animal, including predation, self-defence and intraspecific competition. distributed under the terms and Considering their clinical relevance to humans, snake venoms have been rigorously conditions of the Creative Commons investigated to date. In complete contrast, the evolutionary diversification of venom and Attribution (CC BY) license (https:// venom delivery systems (VDS) in lizards remains relatively underexplored. While certain creativecommons.org/licenses/by/ species of lizards, such as the Gila monster (Heloderma suspectum) and the Mexican beaded 4.0/). lizard (H. horridum), are believed to be capable of inflicting clinically severe envenoming Toxins 2021, 13, 114. https://doi.org/10.3390/toxins13020114 https://www.mdpi.com/journal/toxins Toxins 2021, 13, x FOR PEER REVIEW 2 of 6 Toxins 2021, 13, 114 species of lizards, such as the Gila monster (Heloderma suspectum) and the Mexican beaded 2 of 6 lizard (H. horridum), are believed to be capable of inflicting clinically severe envenoming to humans, and a few others have been suggested to employ venom for predation [9], the to humans, and a few others have been suggested to employ venom for predation [9], the presence of venom in most other lizard lineages is largely undocumented. Nonetheless, presence of venom in most other lizard lineages is largely undocumented. Nonetheless, skinks of the family Scincidae are feared in the rural regions of the Indian subcontinent skinks of the family Scincidae are feared in the rural regions of the Indian subcontinent and are often unnecessarily killed on sight. In support of this fallacious myth, a peculiar and are often unnecessarily killed on sight. In support of this fallacious myth, a peculiar clinical case of neurotoxic envenoming by the common dotted garden skink (Riopa punc- clinical case of neurotoxic envenoming by the common dotted garden skink (Riopa punctata; tata; incorrectly referred to as “the red-tailed skink [Lygosoma punctatum]” by the authors) incorrectly referred to as “the red-tailed skink [Lygosoma punctatum]” by the authors) was was reported from southern India [10]. Considering the potential implications of this reported from southern India [10]. Considering the potential implications of this study study on our understanding of reptilian venom evolution, as well as its negative impact on our understanding of reptilian venom evolution, as well as its negative impact on on conservation, we summarise the scientific evidence that points to the absence of venom conservation, we summarise the scientific evidence that points to the absence of venom in in this enigmatic lineage of lizards and refutes the validity of this clinical report. this enigmatic lineage of lizards and refutes the validity of this clinical report. 2. The Evolutionary2. The Evolutionary Origin of “Toxicofera” Origin of “Toxicofera” Venom Systems Venom Systems Given their significantGiven their role significant in underpinning role in underpinning the evolutionary the evolutionarysuccess of many success animal of many animal lineages, venomslineages, are a venoms fascinating are asystem fascinating for research system in for evolutionary research in evolutionarybiology. The biology.origin The origin and diversificationand diversification of venom, in ofparticular, venom, in has particular, been widely has beeninvestigated. widely investigated. While over a While over a hundred independenthundred independentorigins of venom origins across of venom the breadth across of the the breadth animal of kingdom the animal have kingdom have been traced, thebeen precise traced, origin the precise of venom origin in reptiles of venom is still in reptilesdebated. is Historically, still debated. venom Historically, is venom theorised to ishave theorised independently to have evolved independently twice in evolved reptiles: twice once in in reptiles: Caenophidia once or in Caenophidiaad- or vanced snakesadvanced (Elapidae, snakes Viperidae, (Elapidae, and Viperidae, non-front-fanged and non-front-fanged “Colubridae”) “Colubridae”) and on another and on another time in Helodermatime inlizardsHeloderma (Figurelizards 1) [11–13]. (Figure In1)[ contrast11–13]. to In this, contrast a single to this, early a origin single earlyof origin of venom in thevenom common in theancestor common of the ancestor order ofSerpentes, the order and Serpentes, Anguimorpha and Anguimorpha and Iguania and Iguania lizards, whichlizards, constitutes which the constitutes hypothetical the hypothetical“venomous” “venomous”clade, Toxicofera, clade, has Toxicofera, also been has also been postulated recentlypostulated [14,15]. recently Nonetheless, [14,15]. Nonetheless,given the lack given of evidence the lack for of evidencethe presence for theof presence of venom in Scincidae,venom inthis Scincidae, family is thisnot consid familyered is not venomous considered by venomous either of these by either hypotheses. of these hypotheses. Figure 1. ThisFigure figure 1. depicts This figure (A) the depicts phylogeny (A) the of phylogeny squamate reptilesof squamate with thereptiles single with (red the sphere) single and (red dual sphere) (orange sphere) origins of venomand indicated;dual (orange and sphere) (B) the origins photograph of venom of the indicated; common and dotted (B) gardenthe photograph skink (Riopa of the punctata common). dot- ted garden skink (Riopa punctata). 3. Evidence Supports the Lack of Venom in Scincidae 3. Evidence Supports the Lack of Venom in Scincidae While skinks are feared in the rural regions of India, there are multiple lines of evidence While skinksthat support are feared the lackin the of rural venom regions and efficient of India, VDS there in thisare lineagemultiple [15 lines]. By of employing evi- a multi- dence that supportpronged the strategy, lack of venom involving and venom efficient proteomics, VDS in this venom lineage gland [15]. transcriptomics, By employing evolutionary a multi-prongedanalyses strategy,