Look at these two snakes.
At first glance they look pretty similar: they’re both cobras, both are rearing up
and both are spitting venom at a plastic face.
But you might be surprised to learn that these two seemingly similar snakes are separated
by 14 million years of evolution.
And, back when they diverged, cobras couldn’t spit venom at all. In fact, two different
branches of cobra – African and Asian – and rinkhals all evolved the ability to spit venom
completely independently of each other.
And research into why this happened could unlock secrets not just about the evolution
of snakes and their venom, but about our own evolutionary history too.
There are more than 2,400 species of venomous snake around the world,
with about 400 that pose a threat to humans, and their venom is complex.
One bite from a snake like a puff adder or a saw-scaled viper can contain hundreds of
different toxins that can affect a bite victim in vastly different ways.
Haemotoxins affect blood, cytotoxins and myotoxins destroy cells, muscle, and tissue,
and neurotoxins stop the function of the central nervous system.
However, despite their differences, snake venom has one main purpose:
it’s a weapon to help these predators catch and kill their prey.
But this makes the evolution of venom spitting in cobras a real outlier, and is why scientists
like Nick Casewell at the Liverpool School of Tropical Medicine
have spent years studying it.
"Some cobras spit and some don't, but venom spitting is a defense-specific adaptation
that is unique in the context of snake venom.
This venom spitting enables the snakes to have a long-range mechanism to defend themselves
from predators, as opposed to biting.
Our project focusses on understanding the origin and evolution of venom spitting in
venomous snakes.
We're trying to decipher whether the evolution of spitting has caused the evolution of defensive
toxins that are unique to spitting cobras and, therefore, which will cause
different pathologies to people and animals when they are used."
OK, let’s go back a couple of steps.
Cobras are some of the most iconic snakes in the world, and they have long held an influential
position in human culture.
In ancient Egypt, the uraeus – a rearing cobra – was the embodiment of the powerful
goddess Wadjet, and was worn on the brow of the Pharaoh
as a symbol of his divine right to rule.
In South Asia, cobras were personified as protective deities, and feature in early art
across the continent, from Cambodia to Thailand, and cobras are still revered in India today.
In fact, the Sanskrit word for cobra, nāgá, gives the cobra genus its name, alongside
some famous snakes in popular culture.
Cobras are part of the elapid family, along with mambas, kraits and more than 300 other
species of snake. All have short, immovable, and hollow fangs
found at the front of their mouths.
Elapids are also incredibly venomous. When snakes are ranked by the number of humans
that could be killed by one dose of venom, elapids make up 9 of the top 10.
Elapids probably separated from other snakes about 40 million years ago. Cobras first evolved
in Africa about 11 million years ago, but wouldn’t appear in Asia until
6 million years ago.
This separation of five million years between African and Asian cobras provides scientists
with a timeline from which to study the evolution of these snakes.
There are around 30 species of cobra in the world today. About half of those can spit
venom, plus rinkhals which are not true cobras and belong to a genus of their own.
There are both spitting and non-spitting cobras in Africa and in Asia, but it’s the differences
in venoms between spitters and non-spitters that could hold the answer to whether the
evolution of snake venoms can also be driven by a need to protect themselves.
"When animals use venom for defense, they usually cause quite extensive pain. This is
because pain is a great deterrent; it's a way of getting an animal to leave you alone
and also learn to leave you alone in the future.
It's a bit like when you're stung by a bee. It's trying to get you to leave the nest alone.
And so what we are investigating with our spitting cobras is whether these venoms also
cause extensive pain and inflammation to the eyes of predators, in the same way as a bee
would cause pain when it stings you."
We already know that in Africa there are huge disparities in the effects of bites between
spitting and non-spitting cobras; Non-spitting cobras in Africa cause neurotoxicity which
is typically what elapid snakes do. But, in contrast, African spitting cobras cause extensive
local tissue damage and very little neurotoxicity.
To get a clearer view of why this is the case, and to see if the same differences are there
in the Asian cobras, Nick and his team of researchers have spent over three years collecting
and analysing venom samples.
So, first of all, we have to collect the venoms both from the spitting and non-spitting cobras.
Next, we've been identifying the numerous toxins that are found in these venoms, comparing
and contrasting them to see if there are any patterns that correlate with the ability of
a cobra to spit.
This can be quite a big task as there's between 50 to 200 toxins in each venom.
Because other venomous animals have been shown to exert some form of control over whether
they use offensive or defensive venoms - or, in other words, whether they use different
venom mixtures for different purposes - we have to make sure that the spat venom is the
same as the venom is the same as the venom that's injected from biting.
That's the rationale behind collecting the venoms from individual snakes by prompting
them to spit at this perspex face."
Cobras won’t spit at anything, they aim for the eyes. Hence the Perspex face waved
in front them.
And they don’t just aim for where the eyes are – they can track the short-term movements
of their targets and, like a marksman shooting clay pigeons, anticipate where the eyes are
going to be to maximise their chances of hitting them.
"In one study the red spitting cobra had 100% accuracy at spitting, hitting at least one
eye every time.
This incredible accuracy suggests that the venom's only really useful if it's hitting
somewhere that will cause a lot of damage or a lot of pain.
So our next step is that we've got some collaborators in the University of Queensland, and we're
sending some venoms to them.
They're going to test the venoms on pain receptors. And what we're hoping to see is that the spitting
cobra venom will have a larger effect on these pain receptors than
the non-spitting cobra venom.
This will be quite remarkable because it will be the first evidence of a defensive driver
of evolution in snake venoms."
"We've studied the venoms of eighteen spitting and non-spitting cobras and their close relatives,
and we've found a number of interesting differences between the venoms of those that spit and
those that don't.
These include toxins that can cause death to cells, so-called cytotoxins, which we find
a lot of in the spitting cobras but much less in those that don't spit their venom.
It seems likely that these cytotoxins would cause extensive damage to the eyes,
particularly the cornea, like we see in people who've been spat at by cobras.
And perhaps by causing this cytotoxic cell death in the eye, these venoms are likely
to cause instantaneous pain.
What's really interesting is that venom spitting has evolved on three independent occasions;
in the African spitting cobras, the Asian spitting cobras and the rinkhals.
And this provides us with a comparitive framework so that we can compare whether these different
lineages of spitting cobra have all evolved the same types of defensive toxins, or whether
different lineages of cobras have come up with their own solution for protecting themselves."
This is the phylogenetic tree of the elapid family. It shows how each snake species evolved
in relation to the others. This branch is Naja – the true cobras.
All of these species can rear up and produce a hood when threatened, but only these snakes
can spit their venom.
These are the African cobras, and these are the Asian cobras, and by going back along
the tree we can see where these groups diverged from each other – about 11 million years
ago.
But this is where the tree throws up some surprises: spitting appears in African cobras
first, about 6-10 million years ago but doesn’t evolve in Asian cobras for another 4 million
years or so.
And spitting might have evolved in Rinkhals even earlier – they diverged almost
14 million years ago.
"Despite evolving this ability separately from one another, cobras spit in strikingly
similar ways.
The process of convergent evolution has resulted in all three spitting groups changing the
morphology of their fangs, and perhaps also the chemistry of their venom, so that they
can use it effectively as a long-range defensive weapon.
This suggests that the basic tools, or pre-adaptations, needed to evolve spitting were present throughout
the entire cobra genus."
So, if the tools were there, what triggered the need for such a unique defensive ability?
An early suggestion was that venom spitting evolved for much the same reason rattlesnakes
evolved their rattles – to warn large animals off and avoid getting stepped on.
This would make sense – especially as many cobras share their habitats with the largest
land animals on the planet, and you would imagine they would want to avoid getting trodden
on by herds of buffalo or wildebeest.
The problem with this is that spitting is just too old. The open grasslands of Africa
and its characteristic megafauna didn’t appear until about 5 million years ago, and
we know that spitting evolved at least 6 million years ago.
What’s more, Asian spitting cobras don’t inhabit open grasslands, so are unlikely to
be in a position to get stepped on in the first place.
So if not that, what about predators?
"We know that spitting can be an extremely effective tool for defence, so it stands to
reason that spitting cobras would use it to defend themselves against other predators
or aggressors, but actually there are very few reports of spitting cobras using their
venom against animals other than dogs and humans."
Some scientists actually think that spitting may have evolved in response to the evolution
of primates, hence why they spit at us.
This makes sense, as studies have shown that monkeys and apes are hard-wired to fear snakes,
and many primates – ourselves included – habitually kill snakes for food or because we perceive
them to be a threat.
"But without any direct evidence, ultimately we don't really know the reason that venom
spitting has evolved in just these three groups of snakes and it's this fundamental question
that we're going to try and answer as part of our research."
Nonetheless, while we can’t yet be sure, it’s fascinating to speculate that the arrival
of our own ancestors could have prompted the evolution of one of the most
unique and dramatic defensive abilities on the planet.