broad geographical area. The diet of a snake may also
change ontogenetically, and age-related shifts in venom
composition are also common in such species.In parallel, due to the evolutionary pressure exerted on
animals which are heavily predated upon by venomous
snakes, or indeed predate upon venomous snakes, many
such species evolve resistance. For example, populations
of ground squirrels which are heavily predated upon by
rattlesnakes are able to tolerate significantly higher
doses of venom than are populations of their con-
specifics which inhabit areas absent of these viperine
predators. There are multiple ways in which resistance
can develop; for example through the evolution of a
molecule which is able to inhibit a toxin’s activity, or
through mutations which render a target molecule un-
recognisable to a toxin.These selective pressures exerted reciprocally by preda-
tor and prey drive an ‘evolutionary arms race’: the evolu-
tion of a trait in one driving the evolution of a trait to
counter it in the other. However, as something of a
trump card, many snakes possess toxins in their arsenal
which have evolved to target conserved molecules in
their prey. A conserved molecule is one that has re-
mained unchanged over long periods of evolutionary
time – and for good reason. Typically, such molecules
play an essential role in homeostasis. Therefore, if the
coding gene mutates in a manner that would render the
molecule unrecognisable by the toxin, it most likely also
changes the molecule’s ability to carry out its vital func-
tion. This is a deleterious mutation, harmful to the organ-
ism, and therefore that mutation - and the resistance it
may have conferred - will not persist in the population.So, what is venom?
Ok. So, with a few tangents and caveats along the way,
we have reached the most parsimonious definition
agreed upon by many scientists:‘Venom is a toxic secretion that is produced by specialised
glands or cells of one animal and delivered (usually via a
specialised delivery mechanism) to another animal,
through the infliction of a wound, which disrupts the nor-
mal physiological processes of the receiving animal and
benefits the producing animal.’Right? Well, sorry to disappoint you so close to the finish
line. Cue antimicrobial peptides (AMPs for short). AMPs
are very small proteins (peptides) which are part of the
defensive mucosal skin secretions of many amphibians:
there is no specialised delivery system, and they are toxic
if ingested, so there is little contention surrounding the
classification of such frogs as poisonous. But researchers
investigating the role of AMPs found that they have a
mechanism of action which blurs the line between
venom and poison. Once ingested, they essentially act as
microscopic corkscrews, drilling tiny holes into cell walls
to facilitate the entry of the other toxins into cells and
tissues. Perhaps it could even be argued that the AMPs
are the specialised delivery system.So, what is venom? Venom is a human construct; our
attempt to label a complex array of similar evolutionary
strategies against the will of Mother Nature, who, in her
indifference, reveals herself to be a rebellious teenager,
defying our attempts to neatly define her ways.Above: the Gaboon Viper (Bitis gabonica) has the longest fangs of any venomous snake – up to 5cm in length. It
also has the highest venom yield, with enormous venom glands capable of delivering 5-7ml in a single bite. The
venom itself, however, does not rate as exceedingly toxic, and humans are very seldom bitten, as these snakes
are exceptionally docile and confined to rainforest habitat. Image by Eric Isselee.Antivenom is produced by injecting a host animal,
such as a horse, with increasing amounts of a given
venom (or venoms) over time. The venom toxins are
present in quantities small enough that they do not
cause too much harm, though they are still detected
by the animal’s body as foreign molecules, or antigens.
This triggers a response in the immune system of the
host animal, inducing the production of antibodies.Antibodies are proteins which are able to recognise an
antigenic ‘epitope’: a face, of sorts - a molecular site
unique to that antigen. Each type of antibody is essen-
tially only able to recognise one face - one epitope - and
therefore an antibody is said to be specific to an antigen.
This is why multiple vaccines are required for immunisa-
tion against the influenza virus – each mutated form of
the virus has a different epitope. The ability to recognise
epitopes with such high specificity is what enables the
immune system to differentiate foreign molecules from
normal body molecules. Once an epitope is recognised,
the specific antibody will then bind to the antigenic toxin
which, depending on the toxin structure, either neutral-
ises its harmful activity on the body, or acts as a flag to
immune cells to locate and destroy it.As the bioactivity and structure of the numerous toxins
composing venom differ, each toxin type has different
antigenic properties and a different epitope. Therefore,
each toxin type stimulates the production of toxin-
specific antibodies by the host animal’s immune system.
This cocktail of antibodies is then extracted and purified
from the blood of the host animal, and the resulting
mixture is used as an antivenom. The composition of the
antibodies comprising an antivenom is therefore specific
to the venom or venoms used during the antivenom
production. This is why different antivenoms are needed
for different species of snake. This is also why variation in
venom composition within a single snake species can
seriously compromise the effectiveness of an antivenom.Further, as the immune response does not discriminate
between antigens, antibodies are produced for all
components of venom, regardless of how much harm
they are capable of inducing. Therefore, if too many
different venoms are used to produce an antivenom, the
essential antibodies are diluted by the presence of
non-essential antibodies, thus requiring substantially
more antivenom to achieve the same effect.Antivenom.As a post script to her article on
venom, Bianca op den Brouw
looks at how antivenom works,
and why is it so difficult to achieve
a ‘broad-spectrum’ antivenom?Image by Chuck Rausin.Left: an Irula tribes-
man milks a snake
for antivenom
production at the
Madras Croc Bank.
The Irula Co-op will
feature in an
upcoming article.
Image courtesy
Madras Croc Bank.
Below: variation in
venom composition
can seriously com-
promise the
effectiveness of
antivenom. Image
by Michael Cermak.58