The Secret Behind The Evolution Of Snake Venom Has Finally Been Revealed – via Herp Digest

March 9, 2019, Rob Mitchell, gentside.co, UK

In order to better understand the evolutionary history of snake venom, an international research college investigated the genome of a Japanese specimen, the Okinawa habu.

When taking science to the next level, a certain measure of courage is sometimes needed. Scientists have been collecting DNA samples directly from snake specimens in Japan in order to uncover the mysteries surrounding their venom. They targeted a common snake species from the Ryukyu islands, named after one of the islands in the archipelago: the Okinawa habu. Also called Protobothrops flavoviridis or honhabu, it is the most venomous of the three species of habu found on the island.

Following the courageous act of obtaining venom, blood and skin samples from wild specimens, scientists looked at their genome. Their goal was to better understand the mechanisms involved in the evolution of snake venom. They therefore deconstructed the entire genome of the species using a high-performance sequencer at the Okinawa Institute of Science and Technology.

With this sequencing the researchers were particularly interested in the genes responsible for venom production. They detected sixty of these genes, and were able to determine that they came from 18 different gene families, which were occasionally common to other more distant species. To better understand the usefulness of this discovery, different families of venomous snakes were studied.

The Okinawa habu belongs to the Viperidae family, which has hemotoxic venom that attacks blood cells and tissues. The other big family of poisonous snakes is the Elapidae, which includes the cobra species, which have a neurotoxic venom that attacks the nervous system. Other snake groups exist, but these two categories are the only ones to consist of species that are uniquely venomous.

Researchers have found similarities with the genomes of other species in these different groups. They were able to single out the existence and the position of a common ancestor on the phylogenetic tree, where two different lines of serpents diverged. This snake would have existed a little over 60 million years ago, and the toxins present in the venom of present-day snakes could derive from that of this ancestor.

Scientists went even further back in evolution of snakes. According to the findings of their study, the first appearance of venom was probably 185 million years ago, which corresponds to the time when the Toxicofera ancestor differentiated itself from other scaled reptiles known as Squamates.

In this branch, some lizards in the Autarchoglossa group are also poisonous. Professor Shibata, one of the authors of the study, when explaining this connection says that ‘the gene copies associated with venom production have their origins from long ago, possibly at one of the earliest stages of vertebrate evolution.’

Venoms are complex cocktails composed of many proteins. This research, beyond giving us a better view of its evolution, provides valuable information on the venom of the honhabu, and on how to make more effective antidotes. About 50 people are bitten annually in Japan.

According to the press release, the properties of venoms are also of interest to researchers in order to make new types of drugs, which would potentially be able to fight against cancer, or cardiovascular disease. In the meantime, multiples branches of research on different venomous species should help unravel the enigma of venom production in snakes.

‘Genome decoding is a powerful tool for understanding the mechanisms involved in the evolution of snake venom. We expect that different species of poisonous snakes produce different protein cocktails, derived from new gene arrangements, so decoding the genome of other snakes is essential to understanding the entire evolutionary process,’ said the group of researchers in conclusion.

Chinese snake milkers make $3m selling deadly venom to pharma companies - via Herp Digest

The Hustle 7/13/18

Snake farmers in the tiny Chinese village of Zisiqiao make up to $3m a year by selling snake venom harvested from millions of deadly reptiles, reported the South China Morning Post. 

These farmers sell the profitable poison to large pharmaceutical companies that need the deadly snake juice.

Why do pharma companies need snake venom?

Pharmaceutical companies use real snake venom that is ‘milked’ from live snakes to produce the antivenom that treats potentially lethal snakebites.

The number of people bitten by venomous snakes each year is only increasing from the current 2.7m annually, and that means pharma companies are upping their research and development of antivenom. 

The market for antivenom is expected to rise to $2.95B by 2025, and with it, the demand for venom. 

If you’re hard up for some dollars, go milk a snake

Since snake venom is hard to find and harder to (safely) harvest, communities with lots of scaly squatters reap the financial benefits (a single gram of snake venom is worth around $750).

Since commercial snake farmers can raise millions of snakes at a time, the venom business can reshape local economies. The village of Zisiqiao has a population of 600 people — but, thanks to its 3m serpents, its snake farms generate $12m annually.

Poison pass: the man who became immune to snake venom

Rock singer Steve Ludwin has been injecting himself with snake venom for 30 years. In a strange twist, his bizarre habit could now save thousands of lives. His former partner Britt Collins tells his outlandish story

Britt Collins

Sun 11 Feb 2018 08.00 GMTLast modified on Mon 12 Feb 2018 11.16 GMT

Sometime in 2006, when my ex-boyfriend failed to show up for dinner, I assumed something was wrong or perhaps he’d forgotten. About a week later, calling to apologise, he told me he’d had an overdose, accidentally injecting a lethal cocktail of venom from three snakes. A lot has been written about Steve Ludwin, widely known as the man who injects snake venom, and lately his life has turned into a non-stop frenzy of international journalists and film crews revelling in the seeming sheer insanity of it.

Steve was once my great love; an animal lover, vegan and musician who wrote songs for Placebo and Ash, and played the Reading festival with Nirvana. In between tours and recordings he dabbled with snake venom. In his latest incarnation as a self-taught snake expert, moulding himself into the role of a lifetime, he appears as a kind of living specimen and star in a short film at the Natural History Museum’s new exhibition, Venom: Killer and Cure.

Read more  

Deadly Secret of Snake Venom - via Herp Digest

The world's animals have developed an incredible variety of venoms. But how?

Smithsonian Magazine, May 2015, Emily Anthes

When he returned home to France after a stay in Costa Rica in 1983, Jean-Pierre Rosso carried back an unusual souvenir—a vial of deadly snake venom. Three decades later, after painstaking chemical and neurological analyses, Rosso and colleagues report that two toxins used by Costa Rican coral snakes act like no others, offering new insight into the astonishing array of chemical weapons that have evolved in the world’s animals.When Rosso’s team, led by Pierre Bougis, a biochemist at France’s National Center for Scientific Research, identified the six toxins within the venom, four of them worked as expected, causing paralysis in rodents and other effects. But two were puzzling because they triggered seizures instead.

The first step to understanding the mysterious toxins was to obtain more of the stuff to study in the lab. “I asked many times, ‘Can we get more venom?’” recalls Bougis. But his Costa Rican collaborators, who had initially milked the rare reptile, always replied: “We don’t have snakes.” So the team had to synthesize the toxins, which took a full decade.

The planet is home to more than 100,000 animals with venom, much of which is only now being characterized by scientists. There are not only snakes, spiders and scorpions, but also snails, fish, caterpillars, lizards, squid and even a few mammals, including the platypus, the short-tailed shrew and the slow loris, the world’s only venomous primate.

Because of the great variety, scientists suspect that the adaptation evolved not once but many times. A venomous jellyfish or sea anemone probably came first, maybe 500 million years ago, and venom arose in snakes some 65 million years ago, followed by monotremes (such as the platypus) 46 million years ago. “If we find complex life on other planets,” says Bryan Fry, head of the venom evolution laboratory at the University of Queensland in Australia, “I bet there’s going to be something venomous there.”

Especially if that alien life depends on amino acids. Venom toxins, it turns out, are strings of these basic biological molecules, called peptides or proteins, depending on their size. Scientists speculate that the toxins in venoms weren’t created by animals from scratch but are instead slightly altered versions of everyday peptides and proteins. A simple gene mutation can turn them into toxic weapons.

The French researchers don’t know where the coral snake toxins come from, but once they got hold of enough material, they figured out where the toxins go. The team radioactively tagged the synthetic toxins and applied them to isolated bits of rat brain. The compounds bound so tightly to receptors for a neurotransmitter called GABA that the neurons became overly excited.

Intriguingly, such receptors are involved in human disorders such as epilepsy and chronic pain. Bougis is determined to continue studying the toxins’ interactions with neurons, hoping it will lead to a new understanding of the disorders and perhaps treatments—even if the work takes another decade. “I am...in French, we say, tête dure,” he laughs, “hard-headed.”

Opossum-based antidote to venom from snake bites could save thousands of lives

Date:

March 22, 2015

Source:

American Chemical Society (ACS)

Summary:

Scientists have turned to the opossum to develop a promising new and inexpensive antidote for venomous snake bites. They predict it could save thousands of lives worldwide without the side effects of current treatments.

Continued ...

Mapping snake venom variety reveals unexpected evolutionary pattern (Eastern diamondback rattlesnake Florida panhandle area versus Coral Snake in Southeastern US) - via Herp Digest

Date: January 8, 2015-Source: Genetics Society of America

Venom from an eastern diamondback rattlesnake in the Everglades is distinct from the cocktail of toxins delivered by the same species in the Florida panhandle area, some 500 miles away. But no matter where you go in the Southeastern United States, the venom of the eastern coral snake is always the same. The results of a large-scale survey of venom variation in the two snake species, published January 8, 2015 in the journal Genetics, challenge common assumptions in venom evolution research, provide crucial information for rattlesnake conservation, and will help coral snake antivenom development.

Each venomous snake species produces a unique venom, a mixture of around 50-200 toxic proteins and protein fragments that co-evolve with the typical prey of the snake, such as the smaller reptiles eaten by the eastern coral snake or the rodents preferred by rattlesnakes. In this cycle of evolutionary attack and counterattack, any genetic variants that enhance venom resistance tend to spread through the prey population, prompting tweaks to the snake venom recipe that restore its effectiveness.

The result should be distinctive local co-adaptations between predator and prey, as well as considerable regional diversity in the types and amounts of the different venom proteins. But when Darin Rokyta (Florida State University) and his colleagues collected and profiled venom from eastern coral snakes at many sites within Florida, they found no variation at all. The mix of proteins in coral snake venom from one part of the state was indistinguishable from that collected anywhere else. In contrast, eastern diamondbacks, which live in the same parts of the country as the coral snakes, produce venom with different ratios of toxic proteins in nearly every sub-population across their range. For example, two venom components, including one known to cause paralysis in prey, are found at high levels in the northernmost populations, and were completely absent in the snakes from Caladesi Island, near Tampa.

"We were shocked," Rokyta said. "This is the first time anyone has looked at venom variation at this scale, and everybody has assumed that the co-evolutionary arms race would cause local populations to diverge quickly."

Rokyta says there could be several explanations for the lack of variation in eastern coral snake venom. For example, a small population of the species might have recently expanded and taken over the entire range, displacing other populations and reducing genetic diversity. Or it could reflect a difference in co-evolutionary dynamics between the species and its typically reptilian prey, compared to the small mammals preferred by rattlesnakes. The team is now using genetic clues to the population histories of each species to investigate possible explanations.

The results of the study will be helpful to researchers developing eastern coral snake antivenom. Making an antivenom requires samples of venom, but if the mix varies substantially from place to place, this will affect the drug's effectiveness and reliability. For this species, sampling from many populations should not be necessary. "This tells us it doesn't matter where we catch these relatively elusive snakes; we can stick to using those locations where they're easy to find," Rokyta said.

The variation between eastern diamondback populations could provide crucial information to authorities managing the conservation of this species, which is in decline and under consideration for listing as threatened under the Endangered Species Act. Eastern diamondback rattlesnake declines are thought to have been caused by habitat loss compounded by hunting and persecution by humans. The data from this study can be used for population management, to ensure the full range of venom subtypes are conserved for the long-term viability of the species.

"The received wisdom was that venoms are rapidly-evolving, but now we know that's not necessarily the case." said Mark Johnston, Editor-in-Chief of GENETICS. "Clearly, venom evolution in these two snake species has been shaped by different forces. The next challenge is to understand why."

Story Source:

The above story is based on materials provided by Genetics Society of America. Note: Materials may be edited for content and length.

Journal Reference:

1. M. J. Margres, J. J. McGivern, M. Seavy, K. P. Wray, J. Facente, D. R. Rokyta. Contrasting Modes and Tempos of Venom Expression Evolution in Two Snake Species. Genetics, 2014; DOI: 10.1534/genetics.114.172437

New model for snake venom evolution proposed

Date:

December 8, 2014

Source:

University of Texas at Arlington

Summary:

Researchers have found genetic evidence that highly toxic venom proteins were evolutionarily 'born' from non-toxic genes, which have other ordinary jobs around the body, such as regulation of cellular functions or digestion of food.

Continued ...

Moldovan police and Interpol break up snake venom gang

Police in Moldova working with Interpol officers have broken up a snake venom smuggling gang that operated between Moldova and Afghanistan. The amount of venom seized in the interception was valued at up to 2.8 million Euros.

With closer ties being formed between Moldova and the European Union there is an opportunity for criminal gangs to try and exploit access to a lucrative market. Snake venom is used in the medicinal industry and has a value of between 800 and 2000 euros a gramme on the legitimate market.

Using information and co-operation through Interpol the Moldovan authorities conducted a month-long operation in order to set up the sting operation. Moldovan officers from Moldova General Police Inspectorate, Information and Security Service and General Prosecutor’s Office then moved in and arrested the gang.

They arrested members of the gang in possession of 9,000 vials of snake venom – about 5 kilogrammes – worth over 2.8 million euros. The venom came from snakes such as vipers and other poisonous snakes.

Read more

Biting Back: Snake Venom Contains Toxic Clotting Factors

Feb. 27, 2013 — The powerful venom of the saw-scaled viper Echis carinatus contains both anticoagulants and coagulants finds a study published in the launch edition of BioMed Central's open access journal Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD). These may be a source of potent drugs to treat human disease.

The saw-scaled viper family Echis, responsible for most snake attacks on humans, are recognizable by the 'sizzling' noise they make, produced by rubbing together special serrated scales, when threatened. Echis venom causes coagulopathy, which can result in symptoms ranging from lack of blood clotting, hemorrhage, renal failure and stroke.

Researchers from the Razi Vaccine and Serum Research Institute, Iran led by Hossein Zolfagharian noted that treating plasma with venom from Echis carinatus actually causes it to coagulate. Splitting the venom by ion exchange chromatography showed that then venom

 contained both coagulants and anticoagulants. The clotting factors alone were toxic to mice.

The diametric effects of snake venom on blood are of interest because of medical applications, and although snakes can be considered as dangerous to humans -- they may yet save lives.

Continued:  http://www.sciencedaily.com/releases/2013/02/130226193845.htm

Super-Toxic Snake Venom Could Yield New Painkillers

A bite from the black mamba snake (Dendroaspis polylepis) can kill an adult human within 20 minutes. But mixed in with that toxic venom is a new natural class of compound that could be used to help develop new painkillers.

Named “mambalgins,” these peptides block acute and inflammatory pain in mice as well as morphine does, according to a new study.

Researchers, led by Sylvie Diochot, of the Institute of Molecular and Cellular Pharmacology at Nice University, Sophia Antipolis in France, purified the peptides from the venom and profiled the compounds’ structure. They then were able to test the mambalgins in strains of mice with various genetic tweaks to their pain pathways. Diochot and her colleagues determined that the mambalgins work by blocking an as-yet untargeted set of neurological ion channels associated with pain signals. The findings were published online October 3 in Nature (Scientific American is part of Nature Publishing Group).

As a bonus, mambalgins did not have the risky side effect of respiratory depression that morphine does. And the mice developed less tolerance to them over time than is typical with morphine.

Continued:  http://blogs.scientificamerican.com/observations/2012/10/03/super-toxic-snake-venom-could-yield-new-painkillers/?WT_mc_id=SA_CAT_HLTH_20121009

Snake Genome Suggests Treatments for Human Heart Disease (Via HerpDigest)

Snake Genome Suggests Treatments for Human Heart Disease
By Katherine Harmon Jun 21, 2011 01:10 PM

NORMAN, Okla.-Snakes have been around for some 150 million years, but their ancient physiology might hold some important clues to developing new drugs. 

Aside from their sleek exteriors, snakes' internal physiology is perhaps even more intriguing. "It's a really fun model for studying the extremes of adaptation," Todd Castoe, a researcher at the University of Colorado (CU) School of Medicine's biochemistry and molecular genetics department, said June 20 at the Evolution 2011 annual conference in Norman, Okla.

In addition to the wow-factor of deciphering the snakes' interesting innards, the strange systems could help us better understand our own biology. 

As infrequent feeders, snakes have a highly variable metabolism, which can dip down to one of the lowest-known rates of any vertebrate. In particular, "the Burmese python is the quintessential model of the extreme version of this," Castoe said.

They can increase and decrease their metabolism by some 44-fold and their heart size by more than 50 percent depending on their energy demands. 

Behind all of these unusual evolutionary assets are the genes that make these feats possible. However, even as new genetic sequencing technology has allowed researchers to amass an impressive collection of plant and animal genomes, "reptiles have been really over looked by the bulk of sequencing," Castoe noted.



Earlier this year he and his colleagues published the first draft of a snake genome-the Burmese python (Python molurus bivittatus)-and it has divulged some interesting details about this species' agile metabolism. The snake's mitochondria, which are in charge of energy use in cells, "have undergone the single most extensive change that we're aware of," Castoe said.



To learn more about how the Burmese python heart undergoes such vast changes, Castoe and his team looked specifically at cardiac gene expression. Over the 72-hour metabolic cycle, they found many rapid changes in gene expression in the heart. In just a 24-hour sample, there were 1,852 unique transcriptomes (expressed RNAs in the tissue)-261 of which were up-regulated more than five fold.



These changes might help shed light on human heart development and disease. "We're pretty excited to not look at this in a vacuum," Castoe said. Some heart growth in humans is a good thing, such as that which occurs in childhood and due to exercise-what Castoe calls "Lance Armstrong-style heart growth." But other heart enlargement, such as that caused by heart disease, cardiac hypertrophy, is a definite negative and the target of much drug development. 

"If we are able to understand the genetic cues involved in rapid python heart muscle increases and decreases, that to be says there is the potential to develop therapeutics for humans,"

Leslie Leinwand, director of CU Boulder's Cardiovascular Institute, said in a prepared statement in 2008, before the genome had been completed. 

More work remains to be done before these new findings can be translated into potential drugs for heart disease in humans.

And as researchers digest more of these big snakes' genome, more medical applications might also emerge. 

A second and more thoroughly annotated draft of the python genome is expected out this fall. And other snakes are set to join the ranks of the sequenced, including the garter snake, the rattlesnake and the king cobra. Castoe notes that the field only keeps getting more interesting, adding: "If you're not studying snakes already, you should start."

Chinese village bites into snake business (Via HerpDigest)

Chinese village bites into snake business

By Royston Chan and Aly Song Royston Chan And Aly Song - Sun Jun 19, 9:12 pm ET

ZISIQIAO VILLAGE, China (Reuters Life!) - This sleepy village nestled in the heart of vast farmland in China's eastern Zhejiang province hides a deadly secret.

A step into the homes of any of the farming families here brings visitors eye-to-eye with thousands of some of the world's most feared creatures -- snakes, many of them poisonous.

Cobras, vipers and pythons are everywhere in Zisiqiao, aptly known as the snake village, where the reptiles are deliberately raised for use as food and in traditional medicine, bringing in millions of dollars to a village that otherwise would rely solely on farming.

"As the number one snake village in China, it's impossible for us to raise only one kind of snake," said Yang Hongchang, the 60-year-old farmer who introduced snake breeding to the village decades ago.
"We are researching many kinds of snakes and the methods of breeding them."

In 1985, Yang started selling snakes he caught around the area to animal vendors. He soon began to worry that the wild snakes would run out and thus began researching on how to breed snakes at home.
Within three years, he had made a fortune -- and many other villagers decided to emulate his success.
Today, more than three million snakes are bred in the village every year by the 160 farming families.
Snakes are renowned for their medicinal properties in traditional Chinese medicine and are commonly drunk as soup or wine to boost the person's immunity.

Yang has now started his own company to make his business more formal and build a brand, and also to conduct research and development for his products, which range from dried snake to snake wine and snake powder.

"Our original breeding method has been approved and recognised by the province and the county. They see us as the corporation working with the farming families," Yang said.
"So the company researches on the snakes and they hand them over to the farms for breeding. They said this model was working very well."

The original breeding method was simply putting males and females together, but now meticulous research is done on how the snakes breed, how to select good females, investigation into their diet, and how to incubate eggs so survival rates rise.

With rising demand for snake products from restaurants and medicine halls due both to rising wealth and a government push for breeding the animals to be used in traditional medicine, Zisiqiao villagers are now boasting a annual income of hundreds of thousands of yuan per year.

Yang Xiubang, 46, has been raising snakes in his home for more than twenty years and said his annual income has been steadily rising.

"The demand for traditional Chinese medicine is quite high in China," he said.
"After we finish producing the dried snake, most of them are sent to medicine factories. This also includes snake livers and snake gallbladders."

Yang added snake products from the village are currently being exported globally to countries such as the United States, Germany, Japan and South Korea.

Closer to home, snake products from the village are sold in the bustling Zhejiang city of Hangzhou, where the Hangzhou Woai Company offers a plethora of goods including snake powders.
"Each part of the snake is treasured," said store manager Gao Chenchang.

"China has a strong snake culture, there are a lot of people -- like in Guangzhou -- who like to eat snakes."

With such a special product, Zisiqiao's million dollar business is the envy of other rural communities. But Yang Hongchang said competition is stiff from other breeders who are rearing snakes on a larger scale than his village.

In addition, rearing the snakes comes with obvious risks.

The snake farmers said they had been bitten, some by deadly snakes, and were saved only by injection of anti-venom medicine.

Yang Wenfu, 55, gave up rearing species of venomous vipers after being bitten by one of them earlier in his career.

"After that, I no longer dared to raise vipers. I am still scared today," he said, adding that his arm grew hugely swollen after the bite.

"Life is valuable and making money is secondary."

(Additional reporting by Reuters Television Shanghai; editing by Elaine Lies)

Smugglers Now After Venomous Snakes

by Ajay Kanth, ExpressBuzz
KOCHI: After ivory, ganja and sandalwood, the smugglers are now madly after King Cobra and other venomous snakes in the forests as 10 ml venom of a King Cobra would fetch crores of rupees in the international black market.
The smuggling of snake venom had come to light after the recent seizure of 200 ml of King Cobra venom at Kanjikode, near Palakkad.
"Though the police had earlier information on operation of such rackets, the seizure of 200 ml of King Cobra venom was the first of its kind in the state.
A case has been registered against two persons and a lab analysis report has confirmed it as King Cobra venom," said Crime Branch SP P Vijayan.
He said as per preliminary reports, the venom would be first smuggled to northern parts of the state from where it would be shipped to South-East Asian nations.
"The enzyme in the venom is processed and converted into a drug which will offer an extra kick when taken along with hashish or brown sugar," Vijayan said and added tha t the smuggling of venom had increased in the recent  times as a lot of big buyers had come forward to offer huge money for it.
"Compared to other contrabands, the venom is easy to smuggle as majority of enforcement agencies cannot easily identify it unless and until a lab analysis is done," said a senior police official. Chief Wildlife Warden K
A Ouseph said there had been a lot of reports on venom smuggling and the Forest Department had already conducted several raids at various places.
"We do not think that the smugglers extract venom after catching snakes in the forest.
Reports have pointed out that the smugglers rear snakes at their homes and  at several clandestine places to extract venom from them," the official  said and added that they would further intensify their operation to track those persons who were violating the provisions in the Wildlife Act.

From: HerpDigest Volume # 10 Issue # 46 10/30/10 (A Not-for-Profit  Publication)