One Antivenom for All Snakes? A Potential Lifesaver?

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When Jacob Glanville initially contacted Tim Friede, he stated, “I am eager to obtain some of your blood.”

As Chief Executive Officer of the biotech firm Centivax, Glanville was creating a comprehensive cure for snake poisoning. Friede, on the other hand, is a self-educated herpetologist displaying remarkable resilience to various potent snake poisons present across the globe.

For the duration of the last two decades, Friede encountered over 800 snake attacks and engaged in “self-immunizations” using the toxins from cobras, taipans, black mambas, rattlesnakes, and others. Through the meticulous escalation of diluted venom amounts, he “prepared” his defense system to generate antibodies effective against an expansive selection of snake venom’s dangerous elements.

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Glanville’s requirement for his “universal” antidote was multiple antibodies, each having the capacity to counter various forms of a specific dangerous substance. This presents a considerable challenge, as snake venom encompasses as many as 70 different toxins. Furthermore, the combination, variants, and quantities of these toxins can differ between snake species, even among snakes of the same species from diverse geographical areas. Subtle alterations in the chemical makeup of toxins could result in variable reactions to a snake attack, rendering a specific antivenom ineffective against another snakebite.

However, Glanville believed achieving his goal was still attainable, given that venom toxins are generally variations of roughly 10 protein groups. This implies that the crucial locations where these proteins connect with human cells might display common characteristics across different types of venom.

Glanville suggested that if scientists could discover antibodies capable of attaching to these widespread binding spots, “we might formulate a blend serving as a universal antidote.”

He entertained the notion that the antibodies present in Friede’s blood could target these common sites. Utilizing a 40-milliliter blood sample from Friede, Glanville collaborated with biochemist Peter Kwong and other associates from the National Institutes of Health along with Columbia University, aiming to develop a “broad-spectrum” cure. By 2025, Glanville, Kwong, and their peers announced that, in laboratory mice, a combination of three elements, some derived from antibodies found in Friede’s blood, offered extensive protection against the venom from 19 snakes belonging to the elapid family, composed of around 300 species, including various cobras, mambas, taipans, and kraits.

Glanville suggests his findings demonstrate the attainability of a universal cure. Conversely, certain experts express doubts regarding the necessity and practicality of this approach. They believe that the need is not a “universal antivenom” but rather a collection of several antivenoms, each designed for snakes in a specified geographic area, producible rapidly and affordably.

An Instagram update from Friede, detailing over 800 snake attacks and “self-immunizations”.(@timfriede794)

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A hazardous danger

Figures from the World Health Organization indicate that up to 138,000 individuals perish from venomous snake bites each year, predominantly in Africa, Asia, and Latin America. Such data might be underestimated, considering that those bitten may not always seek medical intervention.

Moreover, acquiring the appropriate antidote rapidly presents a hurdle. Individuals are often unsure about the snake responsible for the attack, particularly given the existence of about 600 types of venomous snakes and the frequent co-occurrence of numerous venomous snake types within a single region.

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Generally, snake venom contains three principal types of toxins: neurotoxins, which injure the nervous system; hemotoxins, which affect blood circulation and clotting; and cytotoxins, which destroy cells and bodily tissue.

Most elapids employ neurotoxins. Amongst the most lethal are three-finger toxins (3FTXs), designated thusly due to the signature finger-like loops present in these protein configurations. The 3FTX family includes both long- and short-chain neurotoxins (LNX and SNX), the most hazardous variants due to their propensity to bind quickly and permanently to receptors located on muscle nerve cells, which inhibits their ability to activate.

Without appropriate countermeasures, 3FTXs can result in swift muscular weakening and mortality.

Developing a universal cure

To formulate their innovative antivenom mixture, Glanville’s group extracted DNA from Friede’s blood, creating a comprehensive archive of antibodies capable of countering snake venom toxins. From this collection, they specifically selected those capable of neutralizing numerous highly dangerous substances.

You don’t make a drug where you take insulin, Alzheimer medicine, cancer medicine, a medicine against bad breath, make it into one pill, and say, hey, [if you] suffer from one of these things, here, just take our multi-drug.

Andreas Hougaard Laustsen-Kiel, the Technical University of Denmark

Kartik Sunagar, an evolutionary geneticist spearheading the Indian Institute of Science’s Evolutionary Venomics Lab and currently working on antivenoms for regional Indian snakes, explained that “antivenoms function by deactivating individual toxins, which then neutralizes the entire venom”. He added, “This is how a broad neutralization can be achieved, as many toxins are universally shared among species.”

Glanville and his colleagues discovered that an antibody known as LNX-D09 was particularly effective against LNXs, while SNX-B03 targeted SNXs. These components were combined with a compound called varespladib, previously identified for its ability to counteract another form of snake venom toxin, phospholipase A2 (PLA2), responsible for the breakdown of cell membranes leading to tissue necrosis, inflammation, hemorrhage, or swelling. This combination successfully protected mice from 19 species of venomous snakes, achieving complete protection against 13 and symptom reduction for the remaining six. Their research was recently published in Cell.

A daunting challenge

Nonetheless, the complexities of snake venoms render developing a single all-encompassing solution particularly difficult.

Andreas Hougaard Laustsen-Kiel, a biotechnologist at the Technical University of Denmark involved in the creation of broad-spectrum snakebite therapies, clarified that “a snake attack does not represent a single disease, and each attack introduces a venom composition that differs”. He added that “the toxins present in African snakes might not exist in any snake venom found across the Americas”.

Laustsen-Kiel refutes the possibility or necessity of a single universal cure for snake venom. In an interview with Live Science, Laustsen-Kiel argued against creating “a single pill by incorporating insulin, Alzheimer’s medication, cancer treatment, and a cure for bad breath to tell people who suffer from these problems to simply consume this multi-drug.”

He similarly cautioned against generating excessive optimism that a “universal” antidote is nearly available. Glanville’s team’s new antivenom cocktail is potent against snakes coming from a wide variety of regions; however, its efficacy remains limited to the venoms examined in the study.

Laustsen-Kiel observed that “to a non-expert, this might appear as broad neutralization, but all species chosen possess similar venom profiles”. He added that close relatives in the study’s regions frequently produce venom with different features than those targeted in the new combination, thereby decreasing its likelihood of success.

A herpetologist harvests venom from an African puff adder to advance antivenom research. According to specialists, developing effective antivenoms will likely need an approach that focuses on venom from snake species localized to specific regions.

He also specified that Glanville and his team’s efforts are meaningful for having validated a strategy in use for the last decade. He said that “making broadly neutralizing antibodies individually and then combining them as cocktails provides a beneficial methodology for formulating improved antivenoms”.

Instead of endeavoring to devise a universal antivenom, he recommends that a superior method would involve combining various broadly neutralizing antibodies customized to particular geographic areas. This approach would involve targeting the venom profiles of snakes indigenous to a particular area, rather than from all over the globe.

The century-old technology behind snake antivenom production

However, another obstacle to an ideal antivenom resides in its production, which still depends on a 125-year-old procedure where animals like horses or sheep are injected with venom, and their antibodies are used for creating antidotes for people. This technique has considerable downsides. For starters, there are not specific antivenoms for the majority of snake species. In cases where they do exist, their effectiveness might differ because of differences in venom. Furthermore, nonhuman antibodies carry the potential to cause allergic responses, such as anaphylaxis and serum sickness, in some people.

In 2024, Laustsen-Kiel stated that what the discipline needs is a way of manufacturing human monoclonal antibodies (mAbs) quickly and efficiently. These lab-designed antibodies would specifically target the human immune system and work against many varieties of the same toxin type.

We might be nearer to that objective than to attaining a universal antivenom. In February 2024, Sunagar and colleagues reported a broadly neutralizing human mAb against a diverse array of LNXs from elapids. Through analyzing over 50 billion synthetic human antibodies, they pinpointed one that was effective. Their findings established a framework for devising more of these types of antivenom therapies.

Sunagar conveyed to Live Science that the key to this broad neutralization is the deactivation of a critical element in snake venom, which consequently neutralizes the entire venom. Thus, only the identification of a specific antibody effective against several venoms possessing similar toxins is necessary.

Their synthetic antibody counteracted whole venoms originating from the king cobra (Ophiophagus hannah) in the Western Ghats region of India, the monocled cobra (Naja kaouthia) located in eastern India, the many-banded krait (Bungarus multicinctus) inhabiting Southeast Asia, as well as the black mamba (Dendroaspis polylepis) found in sub-Saharan Africa.

Sunagar mentioned to Live Science that “broad neutralization is not a concern anymore”. He continued by specifying that “the remaining challenge concerns the mass manufacturing and provisioning of these antibodies to snake projects.”

The higher the quantity of elements an antivenom treatment contains, the greater its cost becomes, rendering its production and distribution in developing nations, where the greatest burden of snake attacks is felt, financially unviable, he elaborated.

Although Glanville holds that a universal antivenom is feasible, his combination has yet to undergo testing in humans. His organization is communicating with an Australian veterinary group to evaluate the cocktail when treating pet dogs for snakebites. They are also evaluating the creation of an equivalent mixture of broadly neutralizing antibodies against the viper family.

Sunagar’s laboratory is pursuing the development of an antibody against vipers indigenous to India. His concept of a universal antivenom is not a single product, falling on the other end of the spectrum.

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