Also known as antivenene or antivenom, antivenin is an antitoxin produced in the blood by repeated injections of venom.
Antivenin for venomous creatures is produced by gradually injecting livestock (usually horses) with the venom of a particular species. The animal gradually produces antibodies to the venom, and its blood plasma is harvested and refined to produce antivenin suitable for use in humans and other animals. This is the only proven method of treating venomous snake bites, and the venom of many other poisonous creatures. The production of antivenin in this way requires constant supplies of venom.
In the late 1800’s, Albert Calmette, a French physician, developed a method of producing antibodies to snake venom by slowly injecting livestock with non-fatal doses of the venom. Regular doses were given, with the volume slowly increasing, until the animal reached a state of “hyper-immunity” to the venom of that particular species of snake. Serum removed from the blood of the animal could transfer immunity to another animal, and reverse the effects of a bite from that snake species.
While various modernisations have been made to the process – it remains essentially the same today as it was over a century ago. The venom is now neutralised before use – the antibodies are still produced, but the animal does not undergo unnecessary suffering. After the serum is removed from the collected blood, the remainder of the blood is transfused back into the animal – preventing dramatic drops in red blood corpuscule and white blood cell count.
Antivenin is produced using the reconstituted freeze-dried venom from each particular snake species in order to gain an antivenin specific to that species. The process is as follows:
An animal (usually a horse in the case of snake antivenins) is injected on a regular basis with increasing non-fatal doses of venom. The venom has been treated to render it less harmful – the treating agent is often formaldehyde. This part of the process lasts from 10 to 12 months. The gradual increase of the tiny amounts of venom allows the animal’s immune system to produce antibodies to the venom. Blood tests determine when this has occurred. Once the animal has become hyper-immune to that form of venom, blood is taken from it – around 6 – 8 litres at a time – nowhere near a life-threatening amount.
The serum is separated from the blood solids – the latter are often transfused back into the animal. The serum is then treated and refined before it is suitable for use in humans. Immunoglobulins in the serum are digested by pepsin to isolate the specific antigen that will neutralise the venom of that species of snake. This product is stored in vials for rehydration for use in treating snake bite.
Polyvalent antivenins are produced by simultaneously exposing the horse to venoms from several different species of snake. They are usually related species whose venom acts in a similar way, and which can all be found in one area. Polyvalent antivenins are often less effective than monovalent (specific to one species) antivenins, but have the advantage that they can be used where the species of the attacking snake is unknown. The two antivenins generally used in the United States are both polyvalent.
Other methods of producing antivenin simply vary the animal used to produce the antibodies. Horses are generally used because their large size makes it easy to administer a non-fatal dose, and to harvest sufficient blood. Sheep are used in one of the main production facilities in the United States, and some work is being done with chickens. The beauty of using chickens to produce antivenins is that the antibodies are found in the eggs of envenomated chickens, and can be separated from the yolks. To create Funnel-web spider antivenin, rabbits are used rather than larger animals. The majority of information available is for snake antivenin. The theory and production is the same for other types of venomous creatures.
More about antivenin:
In Australia alone (ok, so we’ve got a stack of venomous snakes…) there are around 3,000 recorded incidents where humans are bitten by snakes per year. Of these, around 200 to 500 receive antivenin, and on average 2 are fatal. In the United States, around 8,000 people are bitten each year – and around 5 incidents will prove fatal. Surprisingly, in up to 50% of cases no venom is released – and the victim suffers no more than mild discomfort (and the pain of tetanus injections and so forth).
To treat snake bites, up to 40 vials of antivenin can be required for very severe cases. It seems to be that a reasonable amount of antivenin is around 5 – 20 mg for every mg of venom injected – depending on the species of snake. Since the larger snakes can deliver up to 100 mg of venom – a significant amount of antivenin is required. Hundreds of milkings can be required to produce a single dose.
With these figures in mind, it is no wonder that snake venom goes for a fairly hefty price, and that there is a constant shortage of antivenin in the developing nations. Snake venom prices vary, but the Australian Reptile Park – the sole provider of terrestrial species’ venoms to the Commonweath Serum Laboratories – sells dried Eastern brown snake venom for US$2000 per gram.
The shelf life of an antivenin can be up to three years if refrigerated. Antivenin should not be frozen.
Antivenin, while often the only chance for life many bite victims have, is not without its risks. An equine-derived product, the chance of allergic reaction in recipients is alarmingly high. The most common snake antivenin in the United States is Antivenin (Crotalidae) Polyvalent (ACP) – used for rattlesnake, cottonmouth, and copperhead bites. Derived from horse serum, studies have shown that the chance of acute allergic reaction in a recipient (including anaphylaxis) ranges from 23% to 56%. In cases of only slight envenomation, the risk from the antivenin is higher than the risk from the bite itself – and antivenin will not be administered unless necessary. The newer and more expensive antivenin emerging in the states is CroFab – derived from sheep, and demonstrating a far lower incidence of acute allergic reaction – possibly around 14%. The reported risk in Australia was lower still.
Antivenin is always administered in carefully controlled situations, along with a cocktail of antibiotics, antihistamines, tetanus vaccine, and painkillers. It is usually given over a period of time in a saline drip, so that reactions can be monitored and dealt with.
Another phenomenon is “serum sickness” – a delayed reaction to the antivenin. This may occur several days or weeks after treatment, and is found in about half the recipients of antivenin.
Symptoms of serum sickness may include:
A specific antivenin is available for all of Australia and the United States’ most venomous snakes. Polyvalent antivenins cover all of the more obscure species, as far as I was able to ascertain. Sea snakes have specific antivenin, and some species respond well to Tiger snake antivenin. Britain’s only venomous snake: the adder (Vipera berus) has a specific antivenin.
Red back funnel web, and black widow spiders all have specific antivenins, as do scorpions, stone fish and box jellyfish. There is no antivenin for cone shells (conus species) or the Blue ringed octopus.
Basically put – there are very few common venomous animals in the developed countries that do not have a specific antivenin in production. So in general – we’re pretty safe. The risk for collectors and owners of exotic species is higher though - as many of the more rare species have no antivenin.
Thanks to BlakJak and Ascorbic for helping me out with tricky bits of research.