Venom and Antivenom

Milking venom from a Black Whipsnake.

What is a venom?

What is venom? Which animals are venomous? What is venom for? One might think these questions simple, long since resolved by toxinologists – scientists who study toxins, the toxic compounds produced by plants and animals – but few things in nature are ever so simple as they seem. Nature is elegant but messy, complex beyond our wildest dreams, resistant to our attempts to tame it with words and formulas. When we ask what something in nature is for, we are asking a question about its function – what does a particular trait do for an organism that makes it worth having? Why does that organism have that trait? Why did it evolve? It turns out that questions like these have been causing problems for scientists and philosophers for a very long time.

The idea that things in nature have a purpose is often referred to as "teleology.” The word comes from Greek – telos means purpose or goal and logos means knowledge. Teleology, then, is the direction of things towards goals by knowledge. We’re already getting into hot water here aren't we? What's this "knowledge" we’re talking about? Where does it come from? Traditionally, of course, it came from God(s). Little wonder then that many scientists and philosophers have tried to banish the word "teleology" from science altogether. Things in nature have no purpose, they say, they simply are. This is perfectly satisfactory for physics – it makes no sense to ask what the purpose of an electron is – but rather less so for biology. The biologist Theodosius Dobzhansky famously said that "nothing in biology makes sense except in the light of evolution." Dobzhansky was an anti-creationist Christian and although his famous dictum may be a little bit of an overstatement – it's perfectly possible to describe and manipulate things in nature without studying their evolution – it's undeniable that to ignore evolution in biology is to leave rather a lot out. In fact, it's leaving out arguably the most important (and interesting) part, the explanation of how things got to be the way they are.

Enter function (surely it’s no coincidence that function begins with “fun”). In biology, thanks to Darwin's theory of natural selection and its various extensions and refinements, teleology is alive and well. Some prefer the term “teleonomy” (nomos means “law”, thus goal-directed by law), but regardless of terminology it is impossible to deny that organisms have purposes (for example the transmission of genetic information to the next generation) and that their functional traits have evolved to help them achieve these goals. This simple fact is why biology is not a branch of physics and never will be. It goes without saying, of course, that we’re not out of the philosophical woods yet – function remains a tricky concept over which a great deal of ink has been spilled – but at least we've agreed on some basics (right?).

Back to venom. Venom is a functional trait, defined according to the purposes for which it evolved – not just any old toxic substance gets to be called “venom.” Happily, there is fairly widespread consensus regarding the definition of venom itself: it is a mixture of toxic molecules ("toxins", which are mostly proteins) that one organism delivers to another (e.g. by a bite or a sting) for the purpose of defending itself, securing a meal, or deterring a competitor. Venom is a subset of poisons that is "actively delivered.” Yes (pedants, pay attention) – venom is a specialised form of poison. Other poisons might be absorbed across the skin or toxic when ingested, but venom is associated with a specialised delivery system like fangs or a stinger.

So, if scientists agree (for the most part) on what venom is, why can't they agree on which animals have it? Well, the first thing to confess is that we scientists are a disagreeable bunch. That might sound like a bad thing, but I can assure you it's not – it's actually very productive. Strange as it may seem, scientists collaborate by criticising each other's ideas. Knowledge evolves in a superficially similar way to organisms in nature and criticisms are analogous to selection pressures – good ideas withstand criticism; bad (less good) ideas don't and are discarded (or hidden in the bottom drawer). So the fact that toxinologists disagree about which animals to label venomous is a sign that toxinology is a healthy, progressive field. We’ve a lot to learn about venomous critters, so we are all going to be kept very busy criticising each other for the next several lifetimes (even after we upload our consciousnesses onto computer servers).

So what exactly is all this disagreement about anyway? I'm so glad you asked. In the past, there were those who thought that, in order to be labelled as such, venom had to kill animals unlucky enough to be injected with it. As we've learned more about the ways in which organisms use toxins to mess up the regulatory systems of other organisms, it's become clear that causing "rapid prey death" is not a suitable criterion for venomousness. A snake might kill its prey with venom, but what about a wasp that injects a cocktail of toxins directly into the brain of a cockroach, turning it into a passive zombie that allows itself to be led to the wasp’s nest and sealed inside with an egg that will hatch into a larva that will eat the (still unprotesting) cockroach alive? One way the venom of some snakes works is by attacking the blood, turning bite victims into haemophiliacs who die of internal bleeding or catastrophic losses of blood pressure. What about a mosquito or a vampire bat that uses similar toxins to prevent blood from clotting as it sups, but does not kill its prey? Are these blood drinkers venomous?

Things start to get really complicated when we look at closely related animals with venom systems in different stages of evolutionary development. Contrary to certain claims, we don't lack "missing links" in evolutionary biology, we are drowning in them. In some cases, these "evolutionary series" are preserved in extant (surviving today) species. There are snakes with no apparent venom system that are related to species with large, grooved fangs (often towards the back of their mouths) associated with ducts from toxin-producing glands, that are related to snakes with hollow fangs like hypodermic syringes at the front of their mouths and venom glands surrounded by compressor muscles that squeeze them when the snake bites – the classic "high-pressure" venom delivery system. When we look more closely at snakes on the "non-venomous" end of this spectrum, we find that they have glands that are developmentally the same as those of the unequivocally venomous species, just maybe a bit smaller and not associated with compressor muscles. When we look at the oral secretions of these "non-venomous" snakes, we find they contain some of the same proteins that we call "toxins" when we find them in the venoms of front-fanged species. So, are these "non-venomous" snakes actually venomous after all? Where is the line between venomous and not? Are some species “kinda venomous”? Quasi-venomous? Is there a book I can read that can tell me once and for all which snakes are venomous and what happens when we die?

I warned you: nature is messy. Words are digital but nature is analogue. It's important for us to carve nature into categories in order for us to have even the slightest chance of understanding it, but these categories are tools and must be understood as such – nature does not come pre-carved into "natural kinds", no matter what Plato had to say on the subject. In order to understand the evolution of venom, we need to study it as the functional trait that it is. We need to find out what snakes and other animals are using it for. If animals are injecting – using fangs, stingers or any specialised delivery system – toxic compounds into other animals in order to secure a meal or deter predators or competitors, then they are venomous. That means mosquitoes and vampire bats are venomous, as well as wasps and cobras. For many other organisms (including certain snakes and lizards), it will require detailed study of their ecology, alongside study of the secretions they produce, to find out if they are deploying these secretions in a way that would qualify them as venomous. If we want nature to give us answers, we must know how and where to look for them. When we think we’ve found them, we must be prepared for criticism. In order to acquire new knowledge, we must be prepared to be wrong. In order to embrace a scientific worldview must learn to live with uncertainty and even to revel in it – it’s exciting never knowing in advance what one might know tomorrow. We must remain flexible and always remember Orgel’s Second Rule (as formulated by Francis Crick, co-discoverer of the double helix): “evolution is smarter than you are.”

Snake venom and humans

Snake venoms may affect many systems of the body. Common venom effects include paralysis, interference with blood clotting, breakdown of muscle, pain, breakdown of tissues and effects on the cardiorespiratory system (the heart and lungs).

Australian snake venoms may have neurotoxic (paralysing), pro-coagulant (blood clotting) or anticoagulant (blood thinning), and weak cytotoxic (tissue damaging) properties. Some also exhibit potent myotoxic (muscle damaging) activity. The composition of particular venoms influences the clinical presentation of particular snakebites.

Owen Paiva milking a Papuan Taipan. (Photo David Williams)

What is antivenom?

Antivenoms are purified antibodies against venoms or venom components. Antivenoms are produced from antibodies made by animals to injected venoms.  Antivenom is the only definitive treatment for effective bites by venomous Australian snakes. Prior to the availability of antivenom, death ensued in approximately 45% of tiger snake envenomations  and more than 90% of taipan envenomations. The decision to use antivenom should be based on the patient's history, examination and pathologic findings, and the type of antivenom used will depend on geographic, clinical and pathologic factors.

The most commonly used animal in the production of Australian antivenoms is the horse.  Sheep, rabbits and dogs are also currently used in Australia.

How is antivenom made?

Venom is obtained from the various creatures in different ways.  Snakes and funnel web spiders are milked for their venom.  Stonefish, redback spider and box jellyfish antivenoms are made from venom extracted from the animal by dissection.  This may be a dangerous process.

Collecting stonefish and dissecting venomous spines in Papua New Guinea to extract stonefish venom.(Photos M. Kornitschuk, CSL)

Small doses of venom or venom components are injected into the animal, and the dose gradually increased as the animal builds up a tolerance to the venom. In response to the introduction of the venom (a foreign substance), the animal produces antibodies to the venom. When the doses being injected are large, the amount of antibody produced is large.

horse in stable
Collecting blood from immunized horses at CSL Woodend farm.
(Photos K. Winkel)
blood donor bags with horse's blood

These antibodies are harvested by taking blood from the animals and separating out the antibodies, which are then fragmented and purified by a series of digestion and processing steps.

When injected into a patient, the binding sites on the antibody fragments bind to the venoms or venom components in the circulation and neutralize the activity of the venoms in the patient. Antivenoms have been made since the 1890s.

Australia was one of the first countries in the world to experiment with snake antivenoms, in 1898, when Frank Tidswell commenced immunization of a former ambulance horse with tiger snake (N. scutatus) venom.

CSL Ltd is the sole manufacturer of antivenoms for human use in Australia. Australian antivenoms are amongst the best in the world, in terms of purity and adverse reaction rate.

Australian Snake Antivenoms 

Produced in: 

Other Australian Antivenoms

Produced in: 

Tiger snake antivenom

Horses

Funnel web spider antivenom

Rabbits

Brown snake antivenom

Horses

Redback spider antivenom

Horses

Taipan antivenom

Horses

Australian paralysis tick antivenom

Dogs

Black snake antivenom

Horses

Box jellyfish antivenom

Sheep

Death adder antivenom

Horses

Stonefish antivenom

Horses

Sea snake antivenom

Horses

  

Polyvalent snake antivenom

Horses

 

Choice of antivenom: Snake Identification

Identification of the offending snake will aid in the choice of the appropriate antivenom and alert clinicians to particular features characteristic of envenomation by that type of snake.  In cases of snakebite involving zoo staff, herpetologists or other experienced snake handlers, the snake’s identity may be known (although this cannot always be relied upon, particularly in the case of enthusiastic amateurs). Identification of snakes by the general public or by hospital staff is frequently unreliable. Sometimes, the snake is not seen, or is only glimpsed in retreat.