Rethinking Venom Research: How ECIS Could Change the Game

Snakebite is usually framed in terms of death and amputations. But in reality, local tissue destruction and blood-clotting disturbances are far more common outcomes. These are also some of the hardest aspects of envenoming to study. Animal models have long been the default, but they are expensive, ethically fraught, and often poor reflections of what happens in human tissue. In our, we tested a promising alternative: Electrical Cell-Substrate Impedance Sensing (ECIS).

A new window into venom damage

ECIS is a simple but powerful idea. Cells are grown in special wells lined with electrodes. As they attach, spread, and form tight junctions, they generate electrical resistance. Venoms—or potential drugs—can then be added, and the changes in resistance tracked in real time. If the cells detach or die, resistance drops. If an inhibitor works, resistance is preserved. It’s a live window into how cells respond, second by second.

We applied this to six medically important snake venoms: vipers (Agkistrodon contortrix, Crotalus helleri, Vipera ammodytes) and cobras (Naja atra, N. mossambica, N. nigricollis). As expected, all venoms triggered significant cell death and detachment. But what was most striking was how direct toxin inhibitors (DTIs) behaved. Varespladib, which blocks phospholipase A2 (PLA2), and marimastat, which blocks metalloproteinases (SVMPs), both showed protective effects—sometimes individually, often more powerfully in combination.

Matching cell data with clotting data

To put these findings in context, we ran the same venoms through our Stago STA-R Max coagulation analyzer. This let us see the effects on plasma clotting alongside the ECIS cell data. The two datasets aligned beautifully. For example, C. helleri venom was dominated by metalloproteinase-driven tissue damage, and marimastat offered the strongest protection. By contrast, the African spitting cobras’ venom effects were mainly PLA2-driven, and varespladib was highly effective at preserving both cell integrity and clotting function.

Most importantly, the combination of varespladib and marimastat consistently outperformed either drug alone, neutralizing both cytotoxic and coagulotoxic effects across species.

Why this matters

This work shows that ECIS can be a powerful complement—or even an alternative—to animal testing. It is:

• Quantitative, giving real-time traces of venom impact.

• Versatile, able to use any chosen human cell line.

• Ethical, significantly reducing animal use.

• Predictive, aligning closely with clotting data that reflects real-world pathology.

For drug development, this means we can test inhibitors like varespladib and marimastat quickly, cheaply, and with far greater resolution than animal models allow. For venom biology, it offers a new way of dissecting which toxin classes are doing the damage.

Looking ahead

Snakebite research desperately needs methods that are both scientifically rigorous and ethically responsible. ECIS ticks both boxes. Rescue studies—where venoms are added first and inhibitors later—are the next logical step, simulating real-world treatment scenarios. If successful, ECIS could become a standard preclinical tool, accelerating the path to effective field therapies that go beyond antivenoms.

For me, this study underscores a bigger point: toxicology must evolve alongside the venoms we study. With technologies like ECIS, we can move past blunt animal models and into precise, human-relevant assays that get us closer to the real goal—saving lives and limbs.

Here is the link to download the paper

Bite First, Bleed Later: Philippine Pitvipers and the Hidden Dangers of Coagulotoxic Venom

The Philippines is home to a rich diversity of venomous snakes, yet almost nothing is known about how most of their venoms affect the human body. Outside of the Philippine cobra, there are no country-specific antivenoms, and treatment guidelines remain frustratingly vague. In our study, we focused on two Philippine pitvipers—Trimeresurus flavomaculatus and Trimeresurus mcgregori—to uncover what their venoms actually do in the blood, and whether any existing antivenoms can offer protection.

Venoms that make clots—and then break them

Both species’ venoms were able to clot human plasma and fibrinogen much faster than normal. At first glance this might sound like a procoagulant effect. But closer analysis revealed the opposite. The clots formed were weak and unstable, breaking down quickly and depleting fibrinogen levels. This “pseudo-procoagulant” or thrombin-like activity leaves the blood unable to clot properly, creating a net anticoagulant state. The result for a bite victim is a high risk of internal bleeding and hemorrhagic shock.

Adding to the effect, both venoms also inhibited key clotting factors—Factor IXa and Factor Xa. Of the two species, T. mcgregori proved the stronger inhibitor, suggesting it could drive victims into an even more severe anticoagulant state.

Can antivenoms help?

Since the Philippines has no antivenoms for pitviper bites, we tested cross-neutralization by antivenoms made in Thailand. Both the Green Tree PitViper Antivenom (monovalent) and the Hemato Polyvalent Antivenom (raised against several viperid species) were effective to varying degrees. Importantly, the polyvalent antivenom consistently performed better, rescuing fibrinogen clotting more strongly across both species.

This is encouraging. It means that, in the absence of a dedicated Philippine pitviper antivenom, existing Thai antivenoms could provide at least partial protection. For regions of the Philippines where these snakes are common, having access to such products could make the difference between life and death.

A neglected problem

Snakebite is a neglected tropical disease worldwide, and the Philippines illustrates why. There are more than 40 venomous snake species in the archipelago, yet the only available antivenom is for the cobra. Pitviper bites are treated under generic snakebite advisories, leaving clinicians without clear guidance and patients without effective therapy. In rural areas, people often turn to faith healers or traditional remedies simply because hospital care is too far away or too expensive.

Our findings argue strongly that this situation needs to change. At the very least, non-specific but effective antivenoms such as those from Thailand should be stocked in high-risk regions until locally tailored antivenoms can be developed.

The bigger picture

What we see in these Philippine pitvipers is another reminder that snake venoms are sophisticated, dynamic biochemical weapons. They don’t just cause clotting or bleeding in simple ways—they hijack the system, creating unstable clots that collapse into uncontrolled bleeding. For toxinologists, this is fascinating biology. For public health officials, it is a call to action.

Until the Philippines develops its own antivenoms for medically important pitvipers, cross-neutralizing products remain the only lifeline. Better reporting, stronger treatment guidelines, and improved access to effective antivenoms are essential steps if we are to reduce the hidden burden of snakebite across the islands.

Here is the link to download the paper

Baby Saw-Scaled Vipers Rewrite the Rules of Venom

One of the most fascinating aspects of studying venoms is that they are not static. They change with geography, diet, and even the age of the snake. In our study, my team and I uncovered a dramatic example of this in the Egyptian saw-scaled viper (Echis pyramidum pyramidum), one of the deadliest snakes in the world.

Saw-scaled vipers are responsible for countless deaths across Africa and Asia, primarily through a condition called venom-induced consumptive coagulopathy. Their venoms drive the body into catastrophic clotting, depleting clotting factors until victims are left unable to stop bleeding. What hadn’t been investigated until now was whether neonates and adults of the same species deploy their venoms in the same way.

Venoms that grow up with the snake

We compared venom from neonates—just one month old—to that of adults. Both venoms were procoagulant, but the difference in potency was striking. The neonate venom was over 600% more potent than the adult venom in clotting human plasma. Despite delivering smaller amounts of venom, a bite from a neonate could therefore be every bit as medically severe as one from an adult.

The underlying biochemistry also shifted. Neonate venom potently activated Factor VII and Factor X, with some effect on Factor XII. Adult venom, in contrast, barely touched Factor X, was weaker on Factor VII, and only comparable on Factor XII. This is the first time Factor VII and XII activation has been documented in any Echis venom.

Why this matters for treatment

These differences carry direct consequences for snakebite treatment. We tested five different antivenoms and saw a clear pattern: all were less effective against neonate venom. The South African SAVP-Echis antivenom performed the best, but even it neutralized adult venom more efficiently than neonate venom. Others—particularly those raised against West African Echis—barely worked at all.

This highlights a crucial point: most antivenoms are made using venoms from adult snakes. If neonate venoms have different toxins and greater potency, then patients bitten by young snakes may be at even higher risk of poor outcomes. Our results argue strongly that neonate venoms need to be incorporated into immunizing mixtures if we want antivenoms to provide full coverage.

Ecology driving evolution

The ecological story behind this is just as interesting. Juvenile and adult snakes often feed on very different prey. Young Echis take smaller, faster prey such as arthropods and amphibians, where rapid incapacitation is essential. Adults feed on larger mammals, and their venom reflects a slower, but still deadly, strategy. In other words, the venom evolves in step with the snake’s changing ecological niche.

A dynamic biochemical arsenal

This study underscores something I’ve emphasized for years: snake venoms are dynamic evolutionary tools, not fixed traits. They shift across geography, between species, and within an individual’s lifetime. For clinicians, this makes the challenge of developing effective treatments far greater than simply “matching the right species.” For evolutionary biologists, it shows again just how remarkable venoms are as adaptive traits.

Snakebite remains a neglected tropical disease, devastating rural communities across Africa and Asia. By understanding venom variability—including these age-related changes—we can design better antivenoms and, ultimately, save more lives.

Here is the download link for the paper