It can be contended that snakes are one of the most successful animals on earth in terms of their distribution around the globe. Modern snakes are thought to have diverged from lizards around 130 million years ago, in the early Cretaceous period.However, the fossil record for snakes and small lizards is incomplete due to the small and delicate nature of their bones therefore the evolution of snakes is largely based on theory. Snakes diverged from lizards by evolving into smaller and faster predators in order to be more successful in catching quick-moving prey. Rather than evolving to outrun prey, as that takes a great deal of energy, snakes evolved to lie and wait for prey to come along and immobilise it as quickly as possible. The evolution of snake venom from a lizard ancestor made this possible. Snake venom can is saliva containing a mixture of zootoxins (cytotoxins, haemotoxins or neurotoxins) which aid digestion and allow for the immobilisation of prey.
Different types of snakes have different types or combinations of venom. Different evolutionary pressures led to selection of different types of venoms in snakes due to differences in prey and habitat. For example, a snake living in an area where prey can quickly get away, a fast-acting venom is necessary. On the other hand, slow-acting venom would work for prey that cannot get away very quickly, like mice. As well as being split into venomous and non-venomous snakes, venomous snakes can then be further split into Viperids, Elapids and Colubridae. Viperids such as rattlesnakes and vipers are solenoglyphous, meaning that they have hollow fangs which can fold back into their mouth until they are needed. Elapsids such as cobras and mambas are proteroglyphous, meaning that they have fixed front fangs so that when they bite they hang on and chew to envenomate their prey. The Colubridae family contains both non-venomous and venomous snakes, such as boomslangs and vine snakes. They are opisthoglyphous, meaning that their fangs are large teeth at the back of their mouth with a groove for venom to flow down while they swallow their prey.
Cobras have many methods for envenomating their prey. Some spit their venom into a victim’s eyes which can cause blindness and extreme pain. However, this is not as accurate as delivering venom to the victim through their bite. Belonging to the elapsid family, the venom of the cobra contains postsynaptic alpha-neurotoxins that disperse rapidly throughout the bloodstream of the prey and act powerfully on the nervous system. The neurotoxins act as an inhibitor of acetylcholine molecules on the receptor sites of the diaphragm muscle by binding, thus preventing acetylcholine from doing so. In normal circumstances, the acetylcholine molecule binds temporarily during diaphragm contraction causing the channel to open for only around 400 microseconds and then break down during relaxation so that the cycle can start again. The acetylcholine molecule contains an ester group which undergoes a reaction with the -OH group of the receptor site, which allows for its degradation. However, unlike acetylcholine, the neurotoxin will not react instantly with the -OH group, meaning it will remain in the receptor site. This causes the channel to remain open and the electrical impulse drains resulting in the muscle fibre losing sufficient stimulation. Only 1/3 of the receptor sites in the diaphragm need to be blocked for muscle function to be stopped because the response of the muscle is an additive effect. When the muscle stops being able to function, respiratory paralysis occurs and the victim ultimately dies of asphyxiation unless an anti-venom is administered in time.
The venom of the Black Mamba is the most rapidly acting venom of all snake venoms due to its low molecular weight. It contains dendrotoxins, which consist of a single peptide chain of around 60 amino acids. Dendrotoxins bind reversibly to potassium channels and exert an inhibitory effect and results in the cessation of ion conductance. The neurotoxin also binds to the nodes of Ranvier in motor neurons to block the activity of these potassium channels. By binding to the nodes of Ranvier, the duration of the action potential increases therefore the amount of acetylcholine released at the neuromuscular junction also increases. This can result in muscle hyper excitability and convulsions. Ultimately, the progressive hyper excitability of the muscles leads to tetanic contraction causes respiratory paralysis. Furthermore, if the exchange of positive and negative ions is prevented, there can be no nerve impulse, therefore paralysing the nerves and causing death by asphyxiation.
Some rattlesnakes and mamba snakes have fasciculin neurotoxins in their venom. These fast-acting toxins target cholinergic neurons by destroying acetylcholinesterase (AChE). AChE is responsible for breaking down acetylcholine in order to stop it from accumulating in the synaptic cleft. This causes long-lasting and severe fasciculations.
If someone has been bitten by a venomous snake, the crucial thing is to administer the appropriate antivenin. Neurotoxic venoms have to travel further in the body and so it takes longer for the effect to fully establish itself therefore it is easier to treat someone who has been bitten by a snake with neurotoxic venom as opposed to cytotoxic venoms. In order to determine the potency of snake venom, the LD50 must be determined. The LD50 is the lethal dose that kills 50% of the animals (usually mice) in laboratory testing. Antivenin consists of antibodies derived from a host animal which has been hyperimmunised to the venom using non-lethal doses and therefore produced specific antibodies, which are then collected. The antibody used most commonly is immunoglobin G (IgG). The purpose of antivenin is to neutralise the venom and in the case of alpha-neurotoxins, cause it to be released from the receptor site allowing acetylcholine to bind and normal respiration to resume.The venom and antivenin are then removed from the body- despite the rate of release being very slow.
Despite venom being perceived as wholly dangerous to humans, recent studies have shown that snake venom may indeed be a potential contributor for treatment for diseases such as Alzheimer’s Disease. A misfolded protein called amyloid-beta plays a key role in the onset of Alzheimer’s Disease. In a healthy person, amyloid-beta is degraded by enzymes but in the disease, the enzymes are unable to perform their task which causes an accumulation of the toxic protein into deposits of plaque. A study at Monash University (Smith et al, 2016) reported on the discovery of a peptide from the venom of Bothrops asper and undertook experiments using fluorescent imaging to observe interactions between the enzyme and its action on the amyloid-beta plaques. There is still a long way to go until a definite treatment is found for Alzheimer’s disease, but by discovering and characterising enzymes that can stimulate the activity of those in healthy people, more options can be explored and a definite mechanism could be uncovered.
In conclusion, it is evident that the neurotoxins found in snake venom are incredibly harmful to the human body, in particular the respiratory system as a result of the effect on the nervous system. There are a wide range of venoms all suited to a type of snakes environment and evolutionary history and antivenins have been discovered to treat people who have been bitten. There are new applications of snake venom in medicine being discovered and in the future, perhaps it will be a major contributor to the treatment of diseases such as Alzheimer’s disease.