For Snake Bites, There Are Surprising New Discoveries

November 9, 2020 at 7:01 p.m.


A recent issue of Smithsonian magazine described the deadly shortage of venom antidote and what a little known laboratory in Central America is doing about it.  

The laboratory is rising to the challenge of saving thousands of snakebite victims every year. The Instituto Clodomiro Picado, or ICP, named after the father of Costa Rico herpetology (the branch of zoology dealing with reptiles and amphibians), is one of the world’s leading manufacturers of snake antivenoms, and the only one in Central America.  There are only two producers of antivenoms for human use in the United States:  Pfizer (to counteract coral snake venom) and Boston Scientific (to counteract pit vipers like rattlesnakes).   Fortunately ICP fulfills the supply of antivenoms throughout the world where demand is greatest.

Discovery

Antivenoms were first developed at the end of the 19th century by the French physician and immunologist Albert Calmette.  

Calmette, an associate of Louis Pasteur, was stationed in Saigon to produce and distribute smallpox and rabies vaccine to local people.  He was alarmed by a surge of fatal cobra bites in the area.  Calmette – who later gained fame as an inventor of tuberculosis vaccine – applied the principles of immunization and vaccination to snake venom. He injected serial doses into small mammals in order to force their bodies to recognize and gradually develop antibodies as an immune response to the toxins in the venom.  

By 1895, he began producing  the first anitivenoms by inoculating horses with Asian cobra venom, drawing horse’s blood, separating the venom-resistant antibodies and mixing them into a fluid that could be injected into a snakebite victim.

Constituents

Venomous snakes are well known as rich sources of toxins among other venomous species and their venoms are the most highly developed and extremely complex of all natural venoms. Generally, snake venoms are cocktail secretions produced by a pair of specialized exocrine venom glands connected to the fangs by ducts.

Snake venoms are not composed of a single component but instead are complex mixtures of toxic and biologically active proteins and peptides. While some reports demonstrated that around 100 components are present in single venom, it is not known exactly how many proteins and peptides are present in snake venom, but it probably is upwards to about 90–95% of the dry weight of the venom. Some of these proteins exhibit enzymatic activities, whereas several others are non-enzymatic proteins and peptides.

Other components in the snake venom are nucleosides, metallic cations, carbohydrates and very low levels of free amino acids and lipids with less biological activity.  Zinc is needed for activation of anticholinesterase (acetylcholinesterase inhibitor) and calcium is required for phospholipase activity. The presence of cadmium was found to inhibit biological processes in specific enzyme activities. Variation in snake venom composition is found between species, subspecies or even in the same snake specimen.

Snake Bites

Though the exact number of snake bites is unknown, an estimated 5.4 million people are bitten each year with up to 2.7 million envenomings. Around 81,000 to 138,000 people die each year because of snake bites, and around three times as many amputations and other permanent disabilities are caused by snake bites annually.

India alone suffers nearly 50,000 venomous snakebite fatalities each year, chiefly from the saw-scaled viper, the Indian cobra, Russell’s viper and the common krait.   Nigeria’s snakebite mortality rate has been reported at 60 deaths per 100,000 people – more than five times the mortality rate from automobile accidents in the United States.

The snakes that produce the world’s most potent venoms inhabit deserts, tropical forests and warm seas.  Most pose a grave threat to people, but others are seldom encountered.  Ten of the most lethal snakes ranked in descending order by venom potency include the beaked and hook-nosed sea snake, Russell’s viper, inland Taipan, Dobois’ sea snake, Eastern and common brown snake, black mamba, tiger rattlesnake, boomsland,  black and yellow bellied sea snakes and the common Indian or blue krait.

Drug Discoveries

While venomous reptiles have a notorious reputation as dangerous, and sometimes life threatening creatures, their venoms are pointing the way toward entirely new classes of drugs capable of treating diabetes, autoimmune diseases, chronic pain and other conditions.  

Historically, however, snake venom has been used in medicine since the seventh century BCE to prolong life and treat arthritis and gastrointestinal ailments.  Since then, researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements.

Since the development of captopril, the first drug that was derived from Bothrops jararaca, other snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous search for new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents.  

Aggrastat and eptifibatide are two other drugs that were designed based on snake venom components.  Both are used to prevent blood clots. Many other venom components are currently in different clinical stages of development as therapeutic drugs.

Max Sherman is a medical writer and pharmacist retired from the medical device industry.  His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns.  He can be reached by email at  [email protected].



A recent issue of Smithsonian magazine described the deadly shortage of venom antidote and what a little known laboratory in Central America is doing about it.  

The laboratory is rising to the challenge of saving thousands of snakebite victims every year. The Instituto Clodomiro Picado, or ICP, named after the father of Costa Rico herpetology (the branch of zoology dealing with reptiles and amphibians), is one of the world’s leading manufacturers of snake antivenoms, and the only one in Central America.  There are only two producers of antivenoms for human use in the United States:  Pfizer (to counteract coral snake venom) and Boston Scientific (to counteract pit vipers like rattlesnakes).   Fortunately ICP fulfills the supply of antivenoms throughout the world where demand is greatest.

Discovery

Antivenoms were first developed at the end of the 19th century by the French physician and immunologist Albert Calmette.  

Calmette, an associate of Louis Pasteur, was stationed in Saigon to produce and distribute smallpox and rabies vaccine to local people.  He was alarmed by a surge of fatal cobra bites in the area.  Calmette – who later gained fame as an inventor of tuberculosis vaccine – applied the principles of immunization and vaccination to snake venom. He injected serial doses into small mammals in order to force their bodies to recognize and gradually develop antibodies as an immune response to the toxins in the venom.  

By 1895, he began producing  the first anitivenoms by inoculating horses with Asian cobra venom, drawing horse’s blood, separating the venom-resistant antibodies and mixing them into a fluid that could be injected into a snakebite victim.

Constituents

Venomous snakes are well known as rich sources of toxins among other venomous species and their venoms are the most highly developed and extremely complex of all natural venoms. Generally, snake venoms are cocktail secretions produced by a pair of specialized exocrine venom glands connected to the fangs by ducts.

Snake venoms are not composed of a single component but instead are complex mixtures of toxic and biologically active proteins and peptides. While some reports demonstrated that around 100 components are present in single venom, it is not known exactly how many proteins and peptides are present in snake venom, but it probably is upwards to about 90–95% of the dry weight of the venom. Some of these proteins exhibit enzymatic activities, whereas several others are non-enzymatic proteins and peptides.

Other components in the snake venom are nucleosides, metallic cations, carbohydrates and very low levels of free amino acids and lipids with less biological activity.  Zinc is needed for activation of anticholinesterase (acetylcholinesterase inhibitor) and calcium is required for phospholipase activity. The presence of cadmium was found to inhibit biological processes in specific enzyme activities. Variation in snake venom composition is found between species, subspecies or even in the same snake specimen.

Snake Bites

Though the exact number of snake bites is unknown, an estimated 5.4 million people are bitten each year with up to 2.7 million envenomings. Around 81,000 to 138,000 people die each year because of snake bites, and around three times as many amputations and other permanent disabilities are caused by snake bites annually.

India alone suffers nearly 50,000 venomous snakebite fatalities each year, chiefly from the saw-scaled viper, the Indian cobra, Russell’s viper and the common krait.   Nigeria’s snakebite mortality rate has been reported at 60 deaths per 100,000 people – more than five times the mortality rate from automobile accidents in the United States.

The snakes that produce the world’s most potent venoms inhabit deserts, tropical forests and warm seas.  Most pose a grave threat to people, but others are seldom encountered.  Ten of the most lethal snakes ranked in descending order by venom potency include the beaked and hook-nosed sea snake, Russell’s viper, inland Taipan, Dobois’ sea snake, Eastern and common brown snake, black mamba, tiger rattlesnake, boomsland,  black and yellow bellied sea snakes and the common Indian or blue krait.

Drug Discoveries

While venomous reptiles have a notorious reputation as dangerous, and sometimes life threatening creatures, their venoms are pointing the way toward entirely new classes of drugs capable of treating diabetes, autoimmune diseases, chronic pain and other conditions.  

Historically, however, snake venom has been used in medicine since the seventh century BCE to prolong life and treat arthritis and gastrointestinal ailments.  Since then, researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements.

Since the development of captopril, the first drug that was derived from Bothrops jararaca, other snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous search for new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents.  

Aggrastat and eptifibatide are two other drugs that were designed based on snake venom components.  Both are used to prevent blood clots. Many other venom components are currently in different clinical stages of development as therapeutic drugs.

Max Sherman is a medical writer and pharmacist retired from the medical device industry.  His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns.  He can be reached by email at  [email protected].



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