Venom

Snake venoms are complex biochemical cocktails, fine-tuned by natural selection to help snakes immobilize and digest their prey. In simple terms, venom is the means that allow venomous snakes to feed, making it one of their most important evolutionary innovations. Venom is made up of peptides (smaller molecules) and proteins (larger molecules), both often referred to as toxins. Although it may sound intimidating, venom is not as mysterious as many imagine: the venom of a single snake usually contains a few dozen to hundred different toxins and compounds. Each toxin contributes a certain percentage to the overall venom blend, with a small number of dominant toxins accounting for most of the activity. In the case of the Milos viper (Macrovipera schweizeri), the most important groups are: svMP (snake venom metalloproteinases), PLA₂ (phospholipase A₂ enzymes), svSP (snake venom serine proteases), CTL (C-type lectins), DI (disintegrins), LAAO (L-amino acid oxidase). For the average reader, the names themselves are not as important as the key message: a handful of toxin families dominate the venom composition. This is good news for medicine, because it means that antivenoms can be designed to target these main components, efficiently neutralizing the venom’s effects.

There is often some confusion around the terms used to describe the effects of snake venoms—such as neurotoxic, haemotoxic, cytotoxic, or cardiotoxic. These terms are useful, but they can give the false impression that a snake’s venom fits neatly into just one category. In reality, venoms are mixtures, and it is more accurate to say that a species has venom that is predominantly haemotoxic or neurotoxic, without excluding the presence of other toxin types. This means that the symptoms caused by a bite often reflect a combination of toxin families. It is also important to recognize that not all individuals of a species necessarily produce venom with the same composition. In species with wide distributions—across different altitudes, climates, and prey communities—populations may evolve distinct venom profiles in response to local ecological pressures.

For the Milos viper, however, this variability is more limited, since the species is restricted to just four neighboring islands in the western Cyclades (Milos, Kimolos, Polyaigos, and Sifnos). These islands share similar habitats and ecological pressures, which probably results in more consistent venom composition across populations. Another source of variation comes from methodology: venom analyses often rely on samples collected from one population—typically the most accessible one—and results can also be influenced by captivity. Captive snakes often shift from a diverse natural diet of live prey to a simplified diet of thawed rodents, and this dietary change may alter venom composition in the long run.

To overcome these limitations, we have collected and analyzed venom from all four island populations of the Milos viper. A recent study by Schulte et al. (2023) also provided the first insights into the species’ venom composition from captive individuals. Their results confirmed the presence of the main toxin families mentioned earlier (metalloproteinases, phospholipases A₂, serine proteases, C-type lectins, disintegrins, and L-amino acid oxidases). As with other Macrovipera species, the Milos viper’s venom is primarily cytotoxic and coagulotoxic/haemotoxic. Bites involving significant venom injection would therefore be expected to cause pain, swelling (edema), low blood pressure (hypotension), tissue necrosis, consumption coagulopathy, and hemorrhage.

Snakebites from the Milos viper have been recorded in the past, though far fewer than one might expect given the species’ reputation on Milos and Kimolos, where it is often directly confronted by the locals during early Spring. Importantly, there have been no recorded deaths from Milos viper bites in Greece, and only a few incidents are reported each year. Considering that these islands welcome more than 70,000 tourists annually, the actual risk of being bitten is extremely low. Another important point is that not every bite involves venom injection. Many are so-called dry bites with no venom delivered, or involve only a very small amount. This is because venom did not evolve for defense against humans but as a hunting tool for immobilizing and digesting prey as mentioned before. For this reason, snakes rarely "waste" venom on defensive encounters unless they feel severely threatened or are heavily persecuted.

Like all venomous snakes, the Milos viper has two venom glands, which may be full after digestion and rest, completely emptied following the capture of large prey, or at any level in-between. Combined with the snake’s reluctance to use venom defensively, this natural variation further reduces the likelihood of severe symptoms after a bite. In most cases the Milos viper will quickly retreat when encountered, and the only situation where it may hold its ground is when it is surrounded on all sides with no possibility of escape. The danger posed by the Milos viper is therefore often overstated. While caution and respect are always necessary when encountering a venomous snake, the chances of a serious bite on these islands are remarkably low, and much depends on the “luck of the draw” regarding how much venom the snake happens to have available at the time.

Although Greece is home to five viper species (Vipera ammodytes, Vipera berus bosniensis, Vipera graeca, Montivipera xanthina, and Macrovipera schweizeri), the country currently procures only one type of antivenom (AV), raised against the venom of the horned viper (Vipera ammodytes), the most widespread species. This antivenom is a product produced by Bul Bio in Bulgaria and is administered intramuscularly. Unfortunately, intramuscular administration is considered outdated, as modern practice favors intravenous antivenoms that act more rapidly and effectively. In the past, Greece also procured intravenous antivenoms such as VIPERFAV, which would remain the best candidate if a single antivenom were to be used for all five species. Despite its limitations, the Bul Bio product has been used with reported success in treating envenomations from Vipera ammodytes, Montivipera xanthina, and Macrovipera schweizeri. However, patients treated with it often experienced prolonged hospitalization with some symptoms persisting after discharge (e.g. swelling). This raises the question of whether recovery in these cases was due to the antivenom itself, or simply the natural resolution of symptoms combined with supportive care and the low efficacy of intramuscular delivery. Antivenom is not available on any of the islands. Snakebite patients are τυπιψαλλυ transported to whichever hospital is on duty in Athens.

For Macrovipera schweizeri specifically, the most promising antivenom appears to be the Razi Antivenom from Iran, a hexavalent formulation raised against Macrovipera lebetina and Echis carinatus, among others. Additionally, Inoserp European Antivenom (a Pan-African antivenom) has been proposed by Schulte et al. (2023) as another potentially effective option. In both cases, the antivenoms are not raised directly against M. schweizeri venom, but instead show cross-reactivity with venoms of closely related species (Macrovipera lebetina) with similar toxin profiles.

Beyond its clinical effects, the venom of the Milos viper may also hold interest for medicine. Research by Schulte et al. (2023) suggests that the venom shows the ability to inhibit the growth of certain bacterial strains, making it a potential candidate for future bioprospecting programs aimed at developing novel anti-infective compounds. Even without a direct medicinal application, however, the venom of M. schweizeri is of immense value simply as part of our biodiversity, containing a wide array of bioactive molecules shaped by millions of years of evolution. Raising awareness of this hidden biological richness, while at the same time demystifying the species, is vital for its conservation. There is no reason for panic—or even fear—especially considering that during the hot summer months (June to September) the Milos viper is predominantly nocturnal and exceptionally difficult to encounter. Finally, local folklore has long suggested that the “red” phenotype of the species is more dangerous than the “grey.” Venom analyses have shown this to be a myth: there is virtually no difference in venom composition between the two color phenotypes.

This page is not intended to provide medical instructions on treating a Milos viper bite. Instead, it offers general guidance on what to do and what not to do, if you encounter a Milos viper or in the event of a bite. 

Milos viper encounter

In case we encounter a Milos viper in nature:

1. Keep a safe distance of at least two meters. 

2. Do not attempt to kill the snake—not only is this illegal, but you also increase the risk of a defensive bite. 

3. Step back slowly and allow the animal to retreat on its own. 

If a Milos viper is found near your residence :

1. Maintain a minimum two-meter distance, as noted above. 

2. Do not try to kill, touch, or provoke the snake in any way. 

3. If possible, take a photo from a safe distance using your camera’s zoom function (without approaching) 

4. Call the emergency numbers 199 or 100.

5. Keep the snake within sight. 

6. Wait calmly for a qualified expert to remove the animal. 

Milos viper bite

Even if a snakebite occurs, it does not necessarily mean that venom has been injected. In fact, most bites are either ‘dry’ (without venom) or involve only a very small amount. Nevertheless, in all cases of a snakebite, one should immediately seek medical attention at the Health Center (Milos) or Provincial Clinics (Sifnos and Kimolos). Calling in advance will give physicians time to prepare for the patient’s arrival. 

What NOT TO DO in the event of a Milos viper bite:

1. Do not panic. There is no reason to—there are no recorded deaths from Milos viper bites, and symptoms are usually mild.

2. Do not rub, tear, pierce, or cut the bitten area. Leave it alone.

3. Do not tie or constrict the bitten limb to restrict blood flow.

4. Do not apply antiseptics or over-the-counter drugs on the bite site.

5. Do not put ice or hot water on the bite or limb.

6. Do not give alcohol to the patient.

7. Do not administer any drugs (i.e. antibiotics, antihistamines, corticosteroids, or other medications) except paracetamol.

8. Do not give an adrenaline shot.

9. Do not follow traditional remedies even if suggested by locals.

10. Try not to raise the bitten limb above heart level.

What TO DO in the event of a Milos viper bite:

1. Keep calm and avoid panic. 

2. Remove any objects or clothes that may be restricting blood flow in the bittern limb.

3. Keep the patient as still as possible with the bitten limb as relaxed as possible.

4. Position the patient in the most comfortable posture, ideally in the left recovery position, especially if transported in a vehicle.

5. Inform the Health Center or Provincial Clinic if you have not done so already.