Biologist Cipriano Artemilano has this poisonous burrowing scorpion native to the southern Mexican state of Oaxaca.
Gravity separates plasma, which is the antibody-rich part, from the blood plasma.
The venom produced by the stinging of animals such as snakes and scorpions is a silent killer. According to the World Health Organization, nearly 140,000 people die from snake bites each year worldwide. In 2017, WHO added snake venom to the list of widely overlooked "tropical diseases".
Many of them can be treated with antivenoms. That's why mexican researchers have been developing and improving more than a dozen antivenoms used today in the United States and elsewhere throughout the 20th century.
Experts say Mexico has made great strides in drastically reducing the number of snake and scorpion poisoning deaths, while establishing the world's leading antivenom industry, which also provides a replicable model of experience for other countries with high incidence of venomous snake stings.
Poison researcher's ranch
According to National Geographic, the Ocjo de Agua Ranch in Puebla, Mexico, is located on the edge of the sleeping town of Agua Fria and is home to 163 Cleoloma horses. The 400-acre oasis is the legacy of the five brothers, the eldest of whom, Alejandro Aragon, purchased the horses in 2008 with the aim of making anti-venom serum.
Aragon is a toxicologist at the National Autonomous University of Mexico. Since then, he said, these extremely endurance Cleolomas have saved tens of thousands of lives with their precious blood, a key ingredient in making venomous snake bites and other arthropod bites.
Leslie Boyer, a toxicologist at the University of Arizona in the United States, said that in Mexico, scientists "always have a huge incentive to make low-cost, safer anti-venom serums, which are used by hundreds of thousands of people every year because they are safe enough." "Arizona has the highest incidence of animal venom poisoning in the United States.
Aragon has worked extensively with several of the largest antivenom companies, inventing or improving 16 antivenom products, two of which have been approved by the U.S. Food and Drug Administration (FDA).
"In fact, I spend more time in the lab than with my family, but with antivenoms, lives are saved and suffering is reduced," Aragon said. Anti-animal toxins are usually targeted at specific venomous species, including various types of cobras, venomous scorpions, or black widow spiders, and are usually given to patients intravenously.
A serious scorpion sting
One of the top anti-venom research institutes in Mexico is the Institute of Biotechnology of the National Autonomous University. Its amphibian and reptile house is home to 61 endemic and foreign snake species: including the Nayarit coral snake, the Yucatan toucan and the Mexican green rattlesnake. In a smaller room there are scorpions living in boxes.
On a winter's day, the lab's scorpion biologist Zipriano Artemirano demonstrated how arachnids are "milked." He lifted a squirming bark scorpion up with forceps, then dipped it into the water and electrocuted it with a charged copper coil, causing its stingers to spasm, and then the venom oozed out.
The bark scorpion is more venomous, and the species has bitten Aragon twice: once in the laboratory and once in the garden. But in two accidents, he was saved by his own anti-venom.
Scorpion bites have also contributed to the astonishing success of mexico's antivenom industry. In 1995, the son of then-President Ernesto Cedillo was nearly bitten to death by a poisonous scorpion. After that, he mobilized nurses and doctors in health facilities to train in the use of antivenoms, the federal government subsidized the production of antivenoms, and educated rural communities on treatment options, and Cedillo's efforts paid off. According to a 2020 study, from 1990 to 2007, snake bite fatalities decreased by 66 percent and scorpion stings by 83 percent.
Still, scientists have only a certain understanding of how venom works at the molecular level, or how antibodies are formed in immune animals, making it more difficult to build an effective anti-venom serum. That's why Aragon's lab is focused on making anti-virus drugs tailored to individual species.
Conversion from horse blood to antivenom
Since the invention of antivenom in France in 1895, horses have been a major source of blood for the industry. While other mammals can do the same, horses, in addition to having plenty of blood and antibodies, are due to their docile properties. Over a period of six months, the horse was injected with a small amount of venom from a certain animal, which kept increasing until it became immune to the toxin. The rancher then extracts the antibodies and sends them to the lab.
Early in the morning, dozens of horses from the Ocho de Agua Ranch trotted into the feeding area for breakfast, munching on piles of grain. Ranchers in cowboy hats took the animals into spotless stables and tied them to pillars. After sunrise, bloodletting begins.
A technician in a white protective suit applies iodine to a shaved piece of the horse's neck and then tightens its neck with a rope, revealing a vein. As the needle enters, the horse's blood flows through the tube into the hanging bag. It takes 10 minutes to draw five liters of blood. Gravity separates the plasma, which is the antibody-rich part of the blood that gathers on top of the bag to form maroon streaks.
An hour later, the part of the blood without plasma is transported back into the horse through the tube. By the second weekend, the plasma in the bottle became an antivenom. The yield of scorpion antivenom is high, and the yield of one horse can reach 2000 bottles. For african snakes, there are only 200 bottles. Taken together, the farm's 163 horses produce 350,000 bottles of antivenom per year.
Aragon said his horses were all neutered stallions and were treated well: showered weekly, ate organic and vitamin-rich foods, and were monitored for disease. Although these horses initially feel mild pain when they receive venom injections, the symptoms disappear quickly.
Jessica Stark, director of communications and public affairs at World Horse Welfare, a UK-based non-profit organisation, said: "There is no doubt that anti-venoms have tremendous benefits for society. But even under the best conditions, the welfare of horses is affected by repeated injections of toxic substances. We encourage a move to synthetic alternatives as soon as possible. ”
Molecular biology may help drive the production of antivenoms. In 2020, Dutch scientists discovered a way to use stem cells to produce cape coral snake venom. Indian scientists have also recently sequenced the whole genome of cobras, the most comprehensive snake genome to date. These advances could bring scientists closer to synthesizing antivenoms in the lab than on ranches.
"Beautiful mode that can be copied"
Animal venom poisoning is most common in rural areas, particularly in Africa and South Asia, where residents have less access to health care. India has the highest rate of snake bite fatalities in the world with 58,000 deaths per year, followed by sub-Saharan Africa, where about 30,000 people die each year. Scientists believe that more and more human migration, combined with environmental and climate changes, is exposing more people to toxic organisms.
French poison researcher Jean-Philippe Chipper was the first to use the term "vicious circle" to describe the socio-economic processes in which developing countries are caught up in high virulence and low availability of anti-venom serums.
While Mexico broke that cycle and pooled public and private resources, Boyer called it a "great blitzkrieg": adequate funding for the research and manufacture of anti-venoms, nationwide educational programs, investment in modern technology and skilled scientists. However, there is still room for improvement in Mexico: the identification and treatment of venom is still poor, especially in rural areas, and bite cases are greatly underestimated in medical data.
Despite its shortcomings, Mexico has established the world's leading anti-venom industry. Boyer noted that Mexican companies also stay competitive by keeping up-to-date with foreign regulatory requirements and tend to improve drugs based on feedback on the efficacy of their products. This is a sticking point for many developing countries. While challenging, she said it's a beautiful pattern that can be replicated elsewhere.
Compiler: Shi Minglei