Venomous snakes

Snake bites – an overlooked tropical disease

Every year, approximately five million people are bitten by snakes. From these snake bite victims, half are envenomed, with approximately 125,000 people dying and 400,000 ending up with permanent injuries such as amputations (Figure 3) One way to quantify the injuries is disability-adjusted life years (DALYs). DALY is a measure of how many high quality life years are lost as a consequence of deaths and permanent injuries cause by a specific disease. Snake bites cause 6-8 million DALYs annually. In comparison, prostate cancer causes around 7 million DALYs, while hepatitis (liver inflammation) causes approximately 4.5 million DALYs. Most snake bites occur in Latin America, Africa and Asia, and many of the victims are financial caretakers of families. A bite that ends in amputation or death can therefore have serious consequences for the person bitten, but also for their entire family.

Figure 3. Overview of the annual number of bites, injuries and deaths caused by snakes worldwide.

 

Some snakes have lost their venom and instead use strangulation to kill prey. Why do you think this is the case?

Answer: This may be because it is a large energy expense to produce venom.

 

As mentioned, snake venom consists of a complex cocktail of toxins. These toxins are categorised in to three groups based on their mode of action: neurotoxins, hemotoxins and cytotoxins.

  • As the name suggests, Neurotoxins affect the nervous system. For example, there are neurotoxins that block receptors for neurotransmitters, preventing nerve cells from signaling to muscles. In other words, the muscles become paralyzed. If the paralysis affects the respiratory muscles, the victim will suffocate and die unless kept alive with artificial respiration.
  • Hemotoxins affect the heart and blood vessels. Some hemotoxins create holes in blood vessels, causing them to leak, while others can cause formation of blood clots or, conversely, prevent the blood from clotting, causing the victim to bleed to death.
  • Cytotoxins kill cells, often by dissolving cell membranes. Cytotoxins cause large, open wounds. In the worst case scenario, these wounds are so large, that amputation of the injured limb is required.

Therefore, if you are bitten by a venomous snake, it is important to seek medical assistance quickly. The doctor will access, if there are symptoms of envenomation and whether antivenom is needed. It has been over 120 years since antivenom was first invented. However antivenom, that made in much the same way as in 1895, remains the only specific treatment for snakebites. More specifically, antivenoms are made by immunizing a large animal (horses are often used) with small amounts of snake venom (‘immunizing’ is the same as ‘vaccinating’). The animal’s immune system produces antibodies against the venom, and these antibodies can be purified, bottled and later given to snakebite victims as the antivenom.

Across snake species, the venom contains different components, and as a consequence an antivenom only works when it matches the venom. This means that doctors need to know exactly which species of snake the bit the patient, before they can administer an antivenom. Today, this question is answered by examining the patient’s symptoms and asking the patient where and how the bite occurred. Based on the symptoms and knowledge of which snakes are present in the area, doctors can often narrow down which snake is most likely to have bitten and administer the correct antivenom. However, the identification of which snake caused the bite can be difficult, and many doctors are never trained in diagnosing and treating snakebites. There are different kinds of antivenom. Some are polyvalent (i.e. they work against multiple types of snakes), while others are monovalent (i.e. they only work against one type of snake). Polyvalent antivenoms are particularly useful species of snake that caused a bite is unknown. However, much like broad-spectrum antibiotics (which work on many different types of infections), polyvalent antivenoms are not always as effective as monovalent antivenoms, which are highly specific but effective.

Discuss

What are the advantages and disadvantages of the modes of action of the different toxins? Try to include considerations about prey or hunting methods.

 

Which snake is the world’s most dangerous?

Maybe your instinct says, that the snake with the most potent venom is the world’s most dangerous. In that case, the answer to the question “Which snake is the world’s most dangerous?” is the infamous taipan (Oxyuranus spp.). Taipan venom has an LD50 of approximately 0.009 mg/kg when administered intraperitoneally (i.e. in the abdominal cavity, where most organs are located). This means, that the venom from a single bite can kill just short of 2.5 million mice. The taipan’s venom is especially curious, because it provides an example of toxin synergy. In the taipans venom, three toxins of medium-high toxicity collectively form a super toxin called taipoxin. Synergy means that the three components in combination produce a greater effect than if the effects of the individual toxins in isolation were added. Taipoxin can cause permanent damage to nerve endings and therefore permanent paralysis.

Fact box

An example of toxin synergy: If toxins A, B and C individually have potencies of 1, 3 and 2, you might expect that the total potency of 6 for all the toxins combined. However, due to synergy, the toxins are actually stronger together, which is represented here with a total potency of 10.

 

Separate:

Toxin A = 1

Toxin B = 3

Toxin C = 2

A+B+C = 6

 

Compound:

Toxin ABC = 10

 

 

Do the math on LD50: Taipoxin has an LD50 of 1-2 µg/kg, whereas the venom of the common european viper has an LD50 of 0.41 mg/kg. Calculate how many mice 1 mg Taipoxin and 1 mg common european viper venom can kill. Assume a mouse weighs 25 grams.

Answer:

Taipoxin:

First, calculate how many kilograms of mice the venom can kill.

\frac{1000\mu g}{1.5\mu g/kg} = 666.7 \text{ kg mouse}.

Then calculate how many mice the above corresponds to.

\frac{666.7 \, \text{kg}}{0.025 \, \text{kg}} = 26668 \, \text{mouse}

Since we work with LD50 divide the above number of mice by two

\frac{2668}{2} = 13334 \, \text{mouse}

Common european viper:

First, calculate how many kilos of mice the venom can kill

\frac{1 \, \text{mg}}{0.41 \, \text{mg/kg}} = 2.439 \, \text{kg mouse}

Then calculate how many mice the above corresponds to.

\frac{2.439 \, \text{kg}}{0.025 \, \text{kg}} = 98 \, \text{mouse}

Since we work with LD50 divide the above number of mice by two

\frac{98}{2} = 49\, \text{mouse}

 

Although the taipan’s venom is very potent, with a low LD50, taipans not the snake species that causes most human deaths. This dubious honor goes to the carpet vipers (also known as ‘carpet vipers’, ‘saw-scaled vipers’, or by the scientific name ‘Echis‘). Carpet viper have a venom with an LD50 of 0.2-0.4 mg/kg intraperitoneally (i.e. in the abdominal cavity, where most organs are located) and are therefore not nearly as toxic as taipans. On the other hand, they bite more often and are quite agressive in comparison to many other types of snakes. Carpet vipers inject venom in most of their bites, and they are often found in areas inhabited by humans, giving a deadly combination of factors.. The name “carpet viper” actually comes from the snakes’ tendency to hide under carpets. Although only a certain percentage of carpet viper bites are fatal, the sheer number of bites of humans, means that Carpet vipers cause most human deaths.

In yet another view of our question, you could also argue that the most dangerous snake is the one whose bite is the hardest to treat. With this premise, it is snakes such as kraits(Bungarus spp.) and coral snakes(Micrurus spp.) that top the list of dangerous snakes. Kraits, like taipans, have toxins that can permanently damage nerves. This means that if you arrive at the hospital too late, even an antivenom can’t save you. Like kraits and taipans, coral snakes often have a very potent neurotoxic venom. The venom of some coral snakes contains toxins, which still have no antivenom to this day. Adding to the problem coral snakes are difficult to keep in captivity, making it difficult to obtain coral snake venom, that is needed to produce an antivenom.

Figure 4. Kraits has a very potent neurotoxic venom that can cause permanent damage. Image of Lin Tube under the license CC BY 4.0

A wide range of toxic organisms

As previously mentioned, toxic organisms can be found in all corners of nature. Besides snakes, the toxic organisms include scorpions, jellyfish, spiders, snails, amphibians and even mammals. Toxins are found in very distantly related species, implying that the toxic trait is known to have arisen several times during evolution. In addition to toxicity in animals, the list of toxic organisms also include plants. Plant toxicity is different from animal toxicity in the sense that it is almost always used for defensive purposes, as plants are simply trying to protect themselves from herbivores, whereas animal toxicity can also be used to kill prey. Below we will give a brief description of some of the different toxic animal groups. Image examples of the different animal groups can be found in Figure 5.

Spiders

Of the 49,800 spider species in the world, the vast majority are venomous. Despite this huge diversity of venomous spiders, only a small proportion of spiders are actually dangerous to humans. Spiders that can be deadly to humans include funnel-web spiders of the genera Atrax and Trechona, as well as widow spiders(Latrodectus). The spiders with the most potent venom, are often the ones which use their venom to attack, capture and eat prey that is much larger than themselves, such as snakes. Especially spiders from the family Theridiiae are known for this. For example, the widow spiders(Latrodectus) from this family, can eat snakes. The most potent toxin from the widow spiders is α-latrotoxin with an LD50 of 0.0043 mg/kg, see table 1.

For most species of spiders, the bite does not hurt . You’ll just feel a small pinch. However, if you are bitten by the Sydney funnel-web spider(Atrax robustus), one of the world’s most venomous spiders, you may experience symptoms such as increased sweat and saliva production, high blood pressure, increased heart rate, vomiting and goosebumps.

Scorpions

There are more than 2,500 species of scorpions. Their venom contains neurotoxic components, and it is mainly these that make their venoms dangerous for humans. All but one of the human lethal species belong to the family Buthidae. The one deadly species outside of Buthidae is Hemiscorpius lepturus, which causes a lot of scorpion-related deaths. In fact, this species alone is responsible for 67% of all scorpion deaths in Iran. One of the reasons for Hemiscorpius lepturus‘ mortality is that its stings are not associated with pain for the first 24-72 hours. This means that victims don’t seek medical attention until they start to feel symptoms. This is often when the venom has caused so much damage that blood is excreted in the urine. The venom from Hemiscorpius lepturus can cause various symptoms in the body, including: death of tissues and large open wounds, acute kidney failure and destruction of red blood cells.

Frogs

The poison of frogs ranges from barely toxic bufotoxins in toads to more potent toxins in poison dart frogs in the family Dendrobatidae. Most often, the poison comes from the frog’s food, which is why many frogs that are kept in captivity are no longer poisonous, although there are exceptions. An example of a toxin in poison dart frogs is batrachotoxin from the golden poison dart frog(Phyllobates terribilis), one of the world’s most poisonous animals. If you ingest batrachotoxin, it prevents your nervous system from sending impulses, and without these impulses and signals, your muscles don’t work. Certain cells in the heart are highly sensitive to this, resulting in heart rhythm disturbances, fibrillation and heart failure. Batrachotoxin can also be found in table 1 with an LD50 of 0.002-0.007 mg/kg.

Plants

Some plants produce toxins to prevent herbivores from eating them. Since plants cant escape from enemies, evolution has developed this defense method. One example of a poisonous plant is the common foxglove (Digitalis purpurea). The poison mainly contains the two toxins digoxin and digitoxin, which make the heart beat harder at a lower the heart rate. For this reason, it has been used as a heart medicine for over 200 years. Besides its use as a medicine, digoxin is also used to poison people, which can be seen in the James Bond films Casino Royale and No Time to Die and the famous Spanish Netflix series La Casa de Papel (Money Heist). In digoxin poisoning (or overdose), symptoms include low heart rate, vomiting, nausea, uncoordinated heartbeats and, in some cases, cardiac arrest and death.

Marine bristle worms

There are also a number of venomous species among the polychaete worms. For example, fireworms (belonging to the genera Hermodice and Eurythoe), have developed their bristles to cause burning if they are touched. This is a defense against potential predators and can be extremely painful for humans.

Figure 5. Overview of different toxic organisms. Starting from the top left image, you can see the following: Poison dart frog, Black widow spiders, Common foxglove, Deathstalker scorpion and Fireworm. Images by: Renee Grayson, Chuck Evans , Pete Beard , Ester Inbar and NOAA Photo Library . All under the CC BY license

 

Do you think species can lose their venom through evolution and why might this happen?

A: Species can lose their venom in many ways. For example, if the diet or hunting method is changed. Snakes that eat eggs have lost their venom, because they don’t need to immobilize their prey, as eggs are already quite immobilized. Therefore, it “didn’t make sense” evolutionarily to produce a complex, energy expensive venom. Another example is snakes strangling their prey. The capture method of these snakes requires brute strength, not venom.

So when species lose their venom, it’s usually because it no longer gives them an evolutionary benefit to maintain it, and therefore the venom will be nothing but an energetic “cost” to the snake.