54University of Chapter Florida 23 Most Book Toxic of VenomInsect Records W.L. Meyer Chapter 23 Most Toxic Insect Venom

W.L. MEYER Department of Entomology & Nematology University of Florida, Gainesville, Florida 32611-0620 1 May 1996

Insects in the order were recorded as early as the 26th century BC as possessing a venom toxic to vertebrates. Harvester in the have the most toxic venom based on mice LD50 values, with P. maricopa venom being the most toxic. The LD50 value for this species is 0.12 mg/kg injected in- travenously in mice, equivalent to 12 stings kill- ing a 2 kg (4.4 lb) rat. A Pogonomyrmex sp. sting produces intense pain in humans that lasts up to 4 hours. Adult worker of Pogonomyrmex sp. Photo courtesty of J.O. Schmidt A venom is a toxin that is injected into another organism using a specialized apparatus attached oms are chemically described as consisting of to a venom-producing gland. It may be used to alkaloids, terpenes, polysaccharides, biogenic immobilize or kill prey and/or to defend the de- amines (such as histamine), organic acids (for- livering organism against attack by predators. mic acid), and amino acids, but the majority are Venomous are known from the orders peptides and proteins (Schmidt 1986a; Blum Lepidoptera, Hemiptera, and Hymenoptera 1981). The first record of human death attrib- (Blum 1981). The method of delivery may be uted to envenomation by a wasp or hornet was active, such as the sting apparatus of Hy- that of King Menes of Egypt in the 26th century menoptera (bees and wasps), and the mouth- B.C. (Waddell 1930). Toxicity of venoms is dif- parts of Hemiptera (stylets), or passive such as ficult to quantify in an unbiased manner and will the modified setae in some lepidopteran larvae vary among target species. It is also confounded (caterpillars) that are broken on contact and by responses to the venom that are due to im- pierce the outer surface of the receiving organ- mune system disorders (such as hypersensitiv- ism. Schmidt (1982) proposed that some insects ity and allergies). For this reason, morbidity and in the orders Diptera, Neuroptera, and Co- mortality data may not be the best comparative leoptera also possess oral venoms, but there is method to classify venom toxicity (Schmidt a problem with whether this constitutes a true 1986b). I will base my selection of the species venom or is a digestive fluid that is ejected. The of insect with the most toxic venom to verte- biological activity of the venom can be classi- brates based on LD values using mice as the fied as neurotoxic, hemolytic, digestive, hem- 50 test organism. orrhagic and algogenic (pain-producing). Ven- W.L. Meyer Chapter 23 Most Toxic Insect Venom 55

Methods vide an unbiased method of comparing insect Subscribing to the ENTOMO-L bulletin board venoms. and posting a general inquiry about insect ven- Hymenopteran insects possess the most toxic oms was the most profitable first step in obtain- venoms that have been characterized (Schmidt ing information about venomous insect species. 1990; J.O. Schmidt personal communication).

Personal interviews with University of Florida and Table 1 lists the LD50 values for some of these USDA-ARS staff provided often colorful infor- insects that are known to most people, such as mation on people’s ‘favorite’ stinging bug. A wire the , paper wasp, yellowjacket, velvet story (“Killer Caterpillars,” Gainesville Sun, 16 and harvester ants. The most toxic venom is January 1996) apparently was widely distributed found in a species of , Pogono- in newspapers and generated some discussion on myrmex maricopa with a mouse LD50 value of the bulletin board. Searches on LUIS for infor- 0.12 mg/kg (Schmidt et al. 1989; J.O. Schmidt mation on literature in the University of Florida personal communication). Schmidt (1986a) libraries retrieved some secondary literature such states that for a 2 kg mammal only 12 stings are as the book by Blum (1981). Primary literature required to reach the LD50 dose. Other species was identified using references obtained through of Pogonomyrmex also produce venoms with

ENTOMO-L replies and also by searching the low LD50 values when compared with other Hy- AGRICOLA, Current Contents, and MED-LINE menoptera (Table 1). data bases available at University of Florida. Discussion

Results Comparing LD50 values of a test organism (in There were numerous insects suggested for the this case, mice) can be a useful tool to objec- most toxic insect from personal interviews and tively assess the toxicity of insect venoms; how- the ENTOMO-L bulletin board replies, many of ever, this method has its limitations. The values which were based on personal experience and obtained in mice reveal a relative toxicity scale descriptions of the reaction to being envenomed. for different toxins in mice only. They do not Insects suggested included harvester ants (Pogo- reflect how the same toxins would rank for an- nomyrmex; Hymenoptera: Formicidae), bees (Hy- other species (such as humans). For example, menoptera: Apidae), yellowjackets and hornets the LD50 value of P. maricopa venom against a (Vespula, Dolichovespula; Hymenoptera: lizard, Phrynosoma cornutum, which is a preda- Vespidae), velvet ants (Hymenoptera: Mutil- tor of P. maricopa, was much higher than in mice lidae), puss caterpillars (Megalopyge opercularis; (162 mg/kg). When one other lizard, Sceloporus

Lepidoptera: Megalopygidae), slug caterpillars jarrovii, was tested, the venom had an LD50 value (Sibene stimulea; Lepidoptera: Limacodidae), of 28 mg/kg. These results suggest that P. giant silkworm moth caterpillars (Lonomia sp. cornutum has evolved resistance to the harvester and Automeris io; Lepidoptera: Saturniidae) and ant venoms and can exploit the ants as a food assassin bugs (Rasahus sp.; Hemiptera: Reduvi- resource (Schmidt et al. 1989). In another spe- idae). However unpleasant the experience of be- cies of harvester ant, P. badius, there were high ing “stung” by ants, bees, wasps, and assassin bugs levels of an enzyme, phospholipase A2, which is is, it is difficult to quantify pain responses objec- also present in honey bee and wasp venoms tively. Likewise, the perception of the toxicity or (Schmidt & Blum 1978a). Although cross-reac- danger may be artificially inflated when death of tivity to honey bee and wasp venoms may be humans or other verte-brates is the result of en- involved in the response of humans to Pogonomyrmex envenomation, in those cases venomation (Schmidt 1986b). LD50 values pro- 56 Chapter 23 Most Toxic Insect Venom W.L. Meyer

Table 1. LD50 values in mice for toxins found in Hymenoptera.

Family Species Common name LD50 (mg/kg) Reference Apidae Apis mellifera honey bee 2.8 Schmidt 1990 Mutillidae Dasymutilla klugii velvet ant 71 Schmidt et al. 1980 Vespidae Polistes canadensis paper wasp 2.4 Schmidt 1990 Vespidae Vespula squamosa yellowjacket 3.5 Schmidt et al. 1980 Formicidae Pogonomyrmex spp.1 harvester ants 0.66 Schmidt 1990 Formicidae P. maricopa harvester ant 0.12 Schmidt et al. 1989

1 Average of 20 species tested.

that have been studied cross-reactions to vespid logue to current day concepts and practices in and formicid venoms have not been found the diagnosis, treatment, and prevention of in- (Schmidt 1986b). Interestingly, the venom of P. sect sting allergy. Ann. Allergy Asthma badius is not particularly lethal against larval in- Immunol. 74: 198-217. sects (Schmidt & Blum 1978b). Since harvester Schmidt, J. O. 1982. Biochemistry of insect ven- ants are non-predatory, it suggests that their oms. Annu. Rev. Entomol. 27: 339-368. venom has evolved from being used in prey cap- Schmidt, J. O. 1986a. Chemistry, pharma-cology ture as in other ant species (Schmidt 1986a), to and chemical ecology of ant venoms, pp. 425- defense against vertebrates; hence their power 508. In T. Piek [ed.], Venoms of the hy- against humans and other vertebrates. menoptera. Academic Press, London. Acknowledgments Schmidt, J. O. 1986b. Allergy to hymenopteran venoms, pp. 509-546. In T. Piek [ed.], Ven- I thank Dr. Justin Schmidt (Southwestern Bio- oms of the hymenoptera. Academic Press, logical Institute, Tucson, AZ) for his suggestions London. on the most toxic insect, for providing a photo- Schmidt, J. O. 1990. Hymenopteran venoms: graph, and for insights into the literature. I also Striving towards the ultimate defense against thank Dr. Thomas Walker (University of Florida, vertebrates, pp. 387-419. In D. L. Evans & J. Gainesville), Dr. Antonio CastiZeiras and Adrian O. Schmidt [eds.], Insect de-fenses: adaptive Hunsberger, (University of Florida, Homestead), mechanisms and strategies of prey and preda- and Dr. Nancy Epsky (USDA-ARS, Gainesville) tors. SUNY Press, Albany, NY. for critical reviews of the manuscript. Sugges- Schmidt, J. O. & M. S. Blum. 1978a. The bio- tions from two anony-mous reviewers also im- chemical constituents of the venom of the har- proved the manuscript. vester ant, . Comp. References Cited Biochem. Physiol. 61C: 239-247. Blum, M. S. 1981. Chemical defenses in Schmidt, J. O. & M. S. Blum. 1978b. Pharma- . Academic Press. New York. [562 cological and toxicological properties of the p.]. harvester ant, Pogonomyrmex badius, venom. Cohen, S. G. & P. J. Bianchine. 1995. Hy- Toxicon 16: 645-651. menoptera, hypersensitivity, and history: a pro- Schmidt, J. O., M. S. Blum, & W. L. Overal. W.L. Meyer Chapter 23 Most Toxic Insect Venom 57 1980. Comparative lethality of venoms from stinging Hymenoptera. Toxicon 18: 469-474. Schmidt, P. J., W. C. Sherbrooke, & J. O. Schmidt. 1989. The detoxification of ant (Pogonomyrmex) venom by a blood factor in horned lizards (Phrynosoma). Copeia 1989: 603-607. Waddell, L. A. 1930. Egyptian civilization. Summerian origin and real chronology. Luzac, London. [pp. 60-71]. [Not seen, cited in Cohen & Bianchine 1995, p. 201].

Copyright 1996 W. L. Meyer. This chapter may be freely reproduced and distributed for noncommercial purposes. For more information on copyright, see the Preface.