Tuesday, September 21, 2010

The Coral Snake Antivenom Shortage and the Economics of FAB and IgG Antivenoms

We are fast approaching October 31st, 2010.  Besides being Halloween, it is the day when the last batch of Coral Snake antivenom produced by Wyeth goes out of date. Wyeth is now owned by Pfizer. Coral Snake antivenom was first approved for sale in 1967. Wyeth maintained production of whole IgG coral snake antivenom for almost 40 years. However, Wyeth ceased production of antivenom (for both coral snakes and pit vipers) in 2003. Shutting down Wyeth’s antivenom production was highly questionable and surrounded by politics. Wyeth’s operation was not profitable, and the company worked with the FDA to produce a five year supply of antivenom. In 2008 the FDA extended the expiration date on the existing antivenom for a year, and extended it again for another year. Studies on other snake antivenoms have shown it remains effective well passed the expatriation date. Unfortunately, no other pharmaceutical company has come forward to produce the antivenom.

The Mexican drug manufacturer, the  Instituto Bioclon in Huehuetoca, Mexico, has a coral snake antivenom, believe by some to be more effective than Wyeth’s whole IgG antivenom.  Its brand name is  Coralmyn®, and is not currently licensed for sale by the FDA. The tests required for licensing are estimated to cost $3-5 million, and because coral snake envenomation is so rare it could be decades for Bioclon to recover its investment. Coralmyn® is an FAB antivenom, manufactured by taking the whole IgG molecule produced in a horse or sheep and digesting them with an enzyme (pepsin or papain), and then recovering the fragments that bind to the toxins in the snake venom. This type of antivenom is relatively new and is thought to reduce the probability of side effects (anaphylactoid reactions) seen with the whole IgG antivenom used for the past 110 years.

CroFab is the antivenom now used for North American pit viper bites and has been shown to be effective in serious envenomations. However, the economics of the FAB antivenoms versus the whole IgG antivenoms is highly questionable. A vial of FAB antivenom can cost US$1200, while a vial of whole IgG antivenom can be produced for as little as US$40. Whole IgG antivenoms are a century old technology that is highly effective and relatively inexpensive. There is not a lot of money to be made from the production of whole IgG antivenom in the USA because there are relatively few envenomations in any given year. However, if you are the unfortunate person to be bitten, it is your life that is at stake. This is an excellent example of the failure of the market to produce needed medicine, and why medicine for profit is a wrong-headed approach to healthcare. And, yes countries in South America, Africa, and Asia do produce whole IgG antivenoms for reasonable costs and control the side effects with epinephrine that costs about US$2.

Brown, N. and J. Landon, 2010. Antivenom: the most cost-effective treatment in the world? Toxicon 55(7):1405-1407.

Murphy, J. C. 2010. Secrets of the Snake Charmer. Bloomington, 400 pp. (Chapter 6)

Simpson, I. D. and R. L. Norris, 2009. The global snakebite crisis a public-health issue misunderstood, not neglected. Wilderness and Environmental Medicine 20:43-56.

Monday, September 20, 2010

50-million-year-old snake gets a CT scan

The Photo: Lasers lock X-ray beams onto the remains of Clarisse, a 50-million-year-old snake.  Photo by Denny Angelle/The Methodist Hospital System.

The Methodist Hospital , Houston, TX - 9/10/2010

A completely fossilized snake, found in the Fossil Butte region of Wyoming, was brought to Houston, Texas for a CT scan at the Methodist Hospital.  Paleontologist Hussan Zaher professor and curator of the collections of herpetology and paleontology at the Museu de Zoologia of the Universidade de São Paulo in Brazil, worked with the Museum of Natural Science in Houston for the scan.

"Most fossilized remains of snakes are individual pieces of bone," said Zaher. "This is unique because it's a complete snake, which gives us an opportunity to study her makeup and hopefully learn more about her."

CT scan technician Pam Mager conducted the scan on a 64-slice scanner that is capable of sending laser-guided X-rays through a target. "We can take almost 3,000 images in less than a minute," she explained, "and then we can use those images to construct a three-dimensional picture of the snake's bone structure."

Zaher believes this snake could be an evolutionary link between altheonphidian snakes that eat small, elongated prey because they cannot open their mouths widely to swallow large prey and the macrostomate snakes that are capable of eating large prey.

The snake fossil was preserved in limestone, and the entire chunk of rock was placed on the bed of the CT scanner. In less than a minute, the images were taken and assembled by computer into a three-dimensional image that could be rotated 360 degrees.

Taking a preliminary look at the images, Zaher said he saw no traces of limbs. "That places it higher up the evolutionary scale, but the snake is still very old," he said. For more than an hour, he and technician Mager studied the images, looking at tiny details of the snake's skull to find clues to how it may have eaten its prey.

Clarisse is the best preserved Cenozoic snake known in a U.S. scientific collection. According to preliminary analysis, this snake is believed to be closely related to Boavus indelmani, a booid snake described in the late 1930′s. Zaher and the Houston museum hoped that getting a look at the underside of this unique fossil, as well as the inside of bones like the skull would shed some light on the evolutionary history of the species, and its relationship to booid snakes (like pythons and boas).

"This is a very important step in studying this specimen ... I will be able to take away copies of the images for further investigation and I believe this will help us learn about this snake," Zaher said. "I cannot express my gratitude enough to (The Methodist Hospital) and the radiology services department here."

The snake is part of the collection at the Houston Museum of Natural Science and will go on display in 2012.

Friday, September 17, 2010

Bullsnake Home Range

The Bullsnake, Pituophis catenifer sayi.
Home range studies of snakes often look at the available habitat, the size, gender, diet, and ecology of the snake. J. M. Kapfer and colleagues looked at snake home ranges using a different lens. They examined snake home ranges in terms of the quality of its habitats. Using a population of Bullsnakes, Pituophis catenifer sayi, in southwestern Wisconsin. Habitats available to the snakes included agricultural row crop, pasture, agricultural pond, mowed lawn, roadside grass, open grassland, oak savanna, open bluff side, bluff forest, flatland closed canopy forest, and edge habitat. Their results showed that the amount of avoided habitat directly influenced home range size. Radiotracked snakes that used low quality habitats (agricultural row crops and closed canopy forests) often died. Snakes were also able to take advantage of small changes in habitat, one male snake that avoided a pine plantation, used an area of it that was cleared during the study.As snakes increase their home ranges to avoid unsuitable or low quality habitats, they move more and increase the risk of mortality.

Kapfer, J. M. C. W. Parker, D. M. Reineke, J. R. Coggins, and R. Hay. 2010. Modeling the relationship between habitat preferences and home-range size: a case study on a large mobile colubrid snake from North America. Journal of Zoology 282:13-20.

Tuesday, September 14, 2010

A New Chironius from the Tepui’s of the Lost World

Tepuis, the flat-topped mountains of northern South America have produced a fairly large endemic flora and fauna, including many endemic frogs but the discovery of endemic snakes have been far fewer. Now, Philippe J. R. Kok of the Unit of Ecology and Systematics, Vrije Universiteit Brussel, has described a new species of Chiroinus from Maringma Tepui, a flat-topped, sandstone mountain in the Pakaraima Mountains on the Guyana-Brazil border, the snake was found at 1500 m of elevation. Previous specimens of this snake had been collected between 1974 and 2004 but confused with C. fuscus. The new species, Chironius challenger is named after Arthur C. Doyle's fictional character Professor George Edward Challenger in the 1912 novel the The Lost World. It is known from four specimens collected from tepuis in Venezuela and Guyana. The holotype was found in the morning, active in a small tree about 200 cm above the ground in low evergreen upper-montane forest, another specimen had also been collected on the ground on the northeastern slope of Mount Wokomung, also in low evergreen upper-montane forest. Chironius challenger and C. fuscus are superficially similar, but C. challenger differs in having a higher number of ventrals, a lower number of subcaudals, a shorter tail) 9 infralabials instead of 10, an absence of apical pits, an absence of paravertebral keels in juvenile and females. Kok, P. J. R. 2010.  A new species of Chironius Fitzinger, 1826 (Squamata: Colubridae) from the Pantepui region, northeastern South America. Zootaxa 2611:31-33.

Friday, September 10, 2010

Unisexual Vertebrate Species Can Be Ancient

Snake species in many families have been shown to be capable of facultative parthenogenesis, as have some lizards (Varanus). Only one species of snake has been shown to be an all female species, the Flower Pot Snake or Brahminy blindsnake, Ramphotyphlops braminus. But there is another suspected of being an obligate parthenospecies, Dussumier’s Mud Snake, Enhydris dussumierii, a homalopsid from southern India (Murphy, 2007).

Relatively few organisms have abandoned the ability to reproduce sexually. It has long been thought that genetic recombination during meiosis was important in preventing species from accumulating harmful mutations and increasing the probability of survival. However, about 90 species of vertebrates are known to be unisexual, that is reproduction occurs only asexually. A few fish, some amphibians and some squamates are known to be unisexual. Conventional wisdom suggested these were dead end lineages, genetic lines that would be short-lived. Unisexual species were thought to be quite young, formed in an instant through hybridization of closely related species. And, they were considered to be accidental - not every hybridization event could produce a new species. Many of the unisexual species, particularly the whiptail lizards, Aspidoscelis (formerly Cnemidophorus), are obligate pathenospecies, so those harmful mutations will accumulate over time. They were also thought to be maladapted for competing with their parent species and congeners and therefore would be short-lived species in evolutionary time.

Now, Ke Bi and James Bogart (2010) from the University of Guelph, in Ontario have examined the complete mitochondrial genomes as well as markers of a unisexual forms related to Barbour’s Mole Salamander, Ambystoma barbouri. The results supported a monophyletic lineage for the unisexual form that was derived from A. barbouri in western Kentucky. The molecular clock suggests the unisexual lineage originated in the Pliocene, about 5 MYA. Long-lived unisexual species create some confusion.

Lampert and Scharti (2010) asked the question, are the hypotheses about the consequences of absence of genetic recombination wrong, or are the age estimates in error? They suggest the ideas about gene recombination and the dates are both most likely correct and that the solution lies in the specialized ways unisexual vertebrates have circumvented the loss of meiotic recombination in their nuclear genomes. They describe female parthenogenesis as “leaky” and note three ways in which new genetic material can enter a parthenogenetic lineage. In gynogenesis meiotic reduction of chromosomes does not occur, but sperm are needed to trigger embryonic growth, and while the paternal DNA is usually excluded, it is not 100% effective. In a related process, kleptogenesis the maternal genome is on occasion exchanged for the paternal genome, these produce triploid individuals with one set of chromosomes from one parent and two sets from the other. In hybridogenesis haploid oocytes are produced without meiosis and the egg is fertilized by sperm from a closely related species but the male genome is only present in a single generation, and then is excluded from the next generation.

References

Bi, K. and J. P. Bogart. 2010. Time and time again: unisexual salamanders (genus Ambystoma) are the oldest unisexual vertebrates. Biology BMC 2010 10:238.

Lampert, K. P. and M. Scharti. 2010. A little bit is better than nothing: the incomplete parthesogensis of salamanders, frogs and fish. BMC Biology 2010, 8:78.

Murphy, J.C. 2007. Homalopsid Snakes, Evolution in the Mud. Malabar: Krieger Publishing.

Thursday, September 9, 2010

Worldwide Venomous Snakes and Available Venom Antidotes

Worldwide venomous snakes and available venom antidotes is a new database from the World Health Organization. It lists snakes that are venomous worldwide. It also provides venom antidotes that are available for these snakes. The database navigation is on the left side of the page. Just click on “database search”. You can search by region, country, or snake name. You can also search by anti-venom products that are available.

http://apps.who.int/bloodproducts/snakeantivenoms/database/default.htm

Tuesday, September 7, 2010

The Most Recent Battle in the War Against Boiga irregularis

Travis Tritten of the Armed Forces media outlet, Stars and Stripes, reports that dead mice laced with acetaminophen are being dropped from helicopters over Guam’s forest canopy. Each mouse is attached to two squares of cardboard and a streamer of green paper with the idea that bait would catch in the upper tree branches of the jungle. Research found the pain killer to be toxic to the Brown Treesnake (Boiga irregularis) when it was administered orally. Doses of 10, 20, and 40 mg resulted in mortality rates between 50 and 100%, while doses of 20, 40, and 80 mg resulted in mortality rates of 14.3, 85.7, and 100% respectively. About 200 of the baits and some radio transmitters were dropped from a helicopter on 20 acres of Naval Base Guam on Wednesday as a first test of the system, said Dan Vice, assistant state director of USDA Wildlife Services in Hawaii, Guam and the Pacific Islands. Ground traps, were effective in some areas but were impractical in mountainous areas where foot travel is difficult, overcoming the snake’s terrain required a helicopter and a new paper delivery system. “We’ve already found all the baits,” he said. “We will go out over the next few nights and find out their fate.”The USDA has a grant from the Department of Defense to expand the control efforts on Guam military bases in 2011.

Snakes as Healthy Snacks and Meds

A pile of homalopsid snakes, mostly Enhydris enhydris, in a Siem Reap (Cambodia) market. These snakes were being sold for crocodile food and some females have had their bodies opened to show consumers that they are high in fat (eggs and follicles). JCM
Recently it has become clear that people in many parts of the world are consuming an increasing number of snakes. CNN World (June 26,2010) ran a story about cobra meat being harvested for "hamburgers" or perhaps what would better be described as cobrabugers in Yogyakarta, Indonesia.

Since the late 1990's the aquatic snake community at Tonle Sap, Cambodia has been used extensively by local people as a source of protein their farm-raised crocodiles and on occasion human food. Sharon Brooks and colleagues have examined the snake harvest and economics in a series of reports. The most recent one (Brooks et. al. 2010) focuses on the economic aspects of collecting snakes and the associated commercial crocodile trade Tonle Sap. An estimated 2.7 to 12.2 million snakes are consumed by farmed crocodiles annually. However, the market price for crocodiles has declined while the cost of the snakes has risen. Smaller crocodile rearing operations have closed, but the larger crocodile breeding facilities continue to operate under the assumption that crocodile prices will again increase. However, a new market for snakes may be emerging, human snack food. Data on the number of snakes eaten by humans is not available, but Brooks et al. suggest that snake snacks may become more substantial in the future.

Most of the snakes involved in the harvest are homalopsids, and of interest are the reported human health benefits of homalopsid snake oil. Richard Kunin had three species of snakes tested for omega-3 and omega-6 fatty acids: two rattlesnakes Crotalus viridis, Crotalus tigris, and the Chinese Water Snake, Enhydris chinensis. The omega-6 fatty acids have one less double bond than the omega-3's and omega-3 fatty acids are found more frequently in species adapted to cold environments. He found Enhydris chinensis oil contained 20% eicosapentaenoic acid (EPA), about three times more than rattlesnakes. The original snake oil was brought to the USA by Chinese laborers used to build the railroads in the 1840's. Apparently the Chinese recipe contained oil from the Chinese Water Snake, E. chinensis, a member of the tropical snake family Homalopsidae. However, it does have one of the most northerly distributions of the clade and of course feeds almost exclusively on fish. Apparently EPA can be absorbed through the skin, and Kunin suggests that it is a credible anti-inflammatory when topically applied to joints or inflamed skin. Note that I was unaware of this paper, when working on Homalopsid Snakes, Evolution in the Mud. Many homalopsids eat fish and it is entirely possible that more of them contain high concentrations of EPA and related compounds. Thus Kunin's data also suggests that the snake oil products produced in the late 19th century USA that were made from Crotalus would not be particularly effective in treating inflammation. Clark Stanley an American Snake Oil entrepreneur sold snake oil at the 1893  World's Columbian Exposition in Chicago, Stanley entertained crowds chopping up hundreds of rattlesnakes and processing the body fluids into his snake oil, while dressed as a cowboy. The formula for the remedy supposedly came from a Moki Pueblo (AKA Hopi) Indian medicine man. But tests of a federally seized shipment of Stanley’s Snake Oil Liniment showed it to be mostly mineral oil, with one percent fatty oil (probably beef fat), red pepper, and traces amounts of turpentine and camphor (Fowler 1997).Thus, Chinese snake oil may be a useful medicinal compound, while USA snake oil- was just snake oil. And, those Tonle Sap homalopsids, should they prove to have high concentrations of EPA, they may become the healthy protein snack of the 21st century.

References
Brooks, S. et al. 2010. Snake prices and crocodile appetites: aquatic wildlife supply and demand on Tonle Sap Lake, Cambodia. Biological Conservation 143:2127-2135.

Fowler, Gene, ed. 1997. Mystic Healers and Medicine Shows. Santa Fe, New Mexico: Ancient City Press.

Kunin, R. A. 1989. Snake Oil. Western Journal of Medicine 151:208

Sunday, September 5, 2010

Changing From Egg laying to Live Birth

Squamates have evolved from egg layers (the ancestral condition) to live bearers (a derived condition) tens to hundreds of times, in response to environmental changes.It is not at all unusual to find live bearing species in a clade of otherwise egg-laying species. Now Stewart et al. have documented the Australian Yellow-bellied Three-toed Skink, Saiphos equalis, has egg shell thickness that is inversely proportional to the length of time the eggs are retained in the female lizard. In an interview James Stewart, senior author at East Tennessee State University said, "By studying differences among populations that are in different stages of this process, you can begin to put together what looks like the transition from one [birth style] to the other." One of the question related to this is how do evolving species switch from delivering eggs to live babies provide nourishment to the embryos before birth. Some squamates have evolved a placenta, similar to mammals. In egg-laying species, the embryo gets nourishment from the yolk, but calcium absorbed from the porous shell is also an important nutrient source. The shells of these eggs thin dramatically so that the embryos can breathe, until live babies are born covered with only thin membranes—all that remains of the shells. However, a thinner shell has less calcium, which could cause deficiencies for the young reptiles. Stewart and colleagues decided to look for clues to the nutrient problem in the structure and chemistry of the yellow-bellied three-toed skink's uterus. He reports that, "Now we can see that the uterus secretes calcium that becomes incorporated into the embryo—it's basically the early stages of the evolution of a placenta in reptiles." Both birthing styles come with evolutionary tradeoffs: Eggs are more vulnerable to external threats, such as extreme weather and predators, but internal fetuses can be more taxing for the mother. For the skinks, females in balmier climates may opt to conserve their own bodies' resources by depositing eggs on the ground for the final week or so of development. Females in harsh mountain climates, by contrast, might find that it's more efficient to protect their young by keeping them longer inside their bodies. Overall, the results suggest the move from egg-laying to live birth in reptiles is fairly common—at least in historic terms—because it's relatively easy to make the switch, Stewart said. "We tend to think of this as a very complex transition but it's looking like it might be much simpler in some cases than we thought." Stewart. J. R. et al. 2010. Uterine and eggshell structure and histochemistry in a lizard with prolonged uterine egg retention (Lacertilia, Scincidae, Saiphos). Journal of Morphology, DOI: 10.1002/jmor.10877.

Friday, September 3, 2010

Diet of an Ancient Snake

The Amazonian Pipe Snake, Anilus scytale. JCM

The Amazonian Pipe Snake, Anilius scytale, represents a poorly known, ancient lineage of snakes. They are a basal alethinophidian and lack the ability to open their mouth widely. Previous work suggested they feed on elongated amphibians and reptiles. Maschio et al. (2010) examined 162 specimens from the Brazilian Amazonia for food items, only 12% contained prey.  Three species of amphisbaenians (Aulura anomala, Leposternon polystegumn, and Amphisbaena sp.), accounted for 81% of the diet items recovered. The remainder were snakes (Anilius scytale and Tantilla melanocephala) making up 12.5% and caecilians (Caecilia cf. gracilis) composing another 6.25%. They found a positive (but not significant) relationship between the snout-vent length of the pipe snakes and the total length of their prey, with a tendency for smaller specimens to ingest proportionately larger prey. Based upon the prey found, Anilius forages mostly on the ground and in aquatic environments at night. Prey was ingested headfirst, and is likely to minimize the risk of injury. Full citation: Maschio, G. F.,  A. Lúcia da C. Prudente, F. da S. Rodrigues and M. S. Hoogmoed 2010. Food habits of Anilius scytale (Serpentes: Aniliidae) in the Brazilian Amazonia. Zoologia .27(2). This paper can be found on-line at: http://www.scielo.br/scielo.php?pid=S1984-46702010000200005&script=sci_arttext&tlng=en.

File Snake Phylogeny

Acrochordus javanicus. JCM

Filesnakes (Acrochordus) are unusual. They are completely aquatic, living in both fresh and salt water; they have baggy skin with rough scales containing sensory organs; and they the ability to stay underwater for long periods of time. Additionally, they have an Indo-Australian distribution. Three living species are recognized and a fourth species (A. dehmi) is known only from its fossilized vertebrae from Pakistan. One of these, the Elephant Trunk Snake (A. javanicus), is heavily hunted for its skin and meat.  Now, Sanders et al. have estimated divergence times for these snakes and looked at their phylogeny using morphology, fossils, and DNA. Their results show that A. javanicus (a South and Southeastern Asian endemic) is the sister to the Arafura Filesnake (A. arafurae) an Australasian endemic and the widespread, marine Little File Snake (A. granulatus). The divergence of the three extant species was dated at 20.3 MYA (million years ago) and A. granulatus diverged from A. arafurae 15.6 MYA. Their molecular data support the Acrochordids and Colubroidae as sister groups that separated about 62 MYA. Full citation: Sanders, K. L., Mumpuni, A. Hamidy, J. J. Head, and D. J. Gower. 2010. Phylogeny and divergence times of filesnakes (Acrochordus): inferences from morphology, fossils, and three molecular loci. Molecular Phylogenetics and Evolution 56:837-867.

Thursday, September 2, 2010

Lizard SVLs & Weights

Hatchling Anolis sagrei.

Shai Meiri of Tel Aviv University's Department of Zoology has developed a method for translating lizard body lengths to weights. Meiri's new equations calculate this valuable morphological feature to estimate the weight of a lizard species in a variety of different ecosystems.Lizards are frequently important indicator species for understanding the condition of specific ecosystems. Their body weight is a crucial index for evaluating species health, but lizards are seldom weighed, perhaps due in part to the recurring problem of spontaneous tail loss when lizards are in stress. Meir has generate equations to estimate weights from the snout–vent length.And, he used a species-level phylogenetic hypothesis to examine the ecological factors that affect the variation in weight–length relationships. Limbless and reduced limbed lizards are characterized by shallower allometric slopes, and thus long-bodied, legless species are lighter than legged lizards of comparable length. In limbed species the foraging strategy strongly influences the weights, with ambush species being bulkier at comparable lengths than active foraging species. In this study 900 species in 28 different families were used to generated a dataset of lizard weights. Full Citation: Meiri, S. 2010. Length–weight allometries in lizards. Journal of Zoology 281(3):218–226.

Burmese Python Found in Indiana



WXIN, Fox Channel 59 is reporting that an 11 foot Burmese Python was found in Wildcat Creek,in Tippecanoe County, Indiana. The snake was caught by three fishermen. September 1, 2010.

Asian Snakes Playing Dead

A Western Hognose Snake (Heterodon nasicus) displaying 
death feigning behavior. This is a North American snake, I do
not have any photos of Asian snakes death feigning.

Death feigning behavior is known in a number of different snake lineages as well as other groups of vertebrates. It is generally believed to confuse predators so that they abandon the prey. However, another hypothesis suggests that in snakes it is a behavior triggered by the stress of the encounter with the predator. Death feigning may have many different behavioral elements, or just a few. Snake species that feed on toads often have enlarged adrenal glands, and may produce more epinephrine during an encounter with a predator - this in turn may lead to a physiological reaction that result in death feigning. Gernot Vogel and Hans Han-Yuen now report death-feigning behavior in three species of Asian colubrids: Coelognathus radiatus, Macrocalamus chanardi, and Xenochrophis piscator. The authors note that death feigning is known almost exclusively from snakes in the Nearctic, and that the behavior has been reported from only a relatively few snakes in other regions of the world. My view of this is that Nearctic snakes are better studied, there are more herpetologists active in the Nearctic and agree with the authors that many more species will be found to display this behavior.