Wednesday, April 24, 2013

A Death Apple A Day Keeps…..

Biology concepts – toxin, poison, urushiol, oleander, hapten, allergic contact dermatitis

A cloudburst threatens to ruin your summer hike. You dart under a tree for protection from the rain and break out a granola bar. You decide to wait it out, but after a few minutes, your skin starts to itch and your eyes sting. After a few more minutes, you notice a rash on your arms and your throat feels like it's closing. Is it bad granola? Is it acid rain? Are you going to die?

The manchineel tree is toxic enough that just touching it can
do you serious harm. The sign should say, “Don’t even get
near me!” because dripping sap can be just as bad. On the
right you see the apples of the manchineel. They look good,
they are sweet, and the price is right – and then you die.
No, no, and maybe. You just picked the wrong tree to use as an umbrella. This is the manchineel tree (Hippomane manciella), native to several countries in the around the Americas and the Caribbean.

The latex that oozes from this tree contains the toxins hippomanin A and B. Both toxins are present in the latex, leaves, bark, wood, roots, fruit, flowers, and nectar of the manchineel. Eat it or rub against it, and you get sick. Cut it up and the sawdust makes you sick; get it in your eyes (even the smoke from burning it) and you can go blind!

Most deaths have occurred from eating the apple of the manchineel; hence the common name for the tree – the Death Apple. Your mucosal surfaces blister, your larynx swells shut, your GI system rebels loudly and explosively. Massive hemorrhage can follow the closing of your throat, so you drown in your own blood.

In the 1500’s, South American Indians threw death apples down their own wells to poison the invading Spanish conquistadors. It worked because this toxic plant is an exception; it is sweet. Most often, plant toxins taste bitter and that's how we know to avoid them. The death apple’s taste prevents us from making a judgment that could save our life. Definitely, this is a plant to be respected and feared.

Now that I have your attention, let’s talk about a seemingly more common plant toxin. Urushiol is the name for the offending group of molecules in poison ivy, poison oak, poison sumac, even more exotic plants like mango, lacquer trees and cashew nuts.

Mangoes (left) and cashews (right) are in the same family
of plants as poison ivy and poison oak. They contain
urushiol and can cause significant damage to those who have
a heightened allergic response. Urushiol is present in the
skin of the mango fruit and in the shell of the cashew nut.
This is why you can’t buy cashews in the shell, the shell
must be removed to make them safe. Cutting a mango will
give you a small exposure, but most people tolerate this well.
The urushiol (Japanese for lacquer) is exuded from the leaves and stems of the offending plants, and is found in the cashew nut shell. Skin contact leads to blisters and a rash; these are seen earlier in patches that get a larger dose. Urushiol is only partly water soluble, so it can stay on the skin or other surfaces and be spread for quite a while. It can stay on clothes until they are washed; even if that may be years, as in the case with my teenagers.

Urushiol toxicity comes from the immune reaction it generates in about 60-80% of the population. However, urushiol doesn’t spark an immune response on its own. It turns your body against itself. Immune responses are aimed at antigens (not born of, so not self), but urushiol breakdown products are haptens (to fasten to); think of them as half antigens. Haptens must combine with something else to become full antigens. In the case of urushiol, they combine with proteins from our own cell membranes.

When portion of the urushiol combines with the integral protein, now the protein is seen as foreign and your immune system might start to attack, in a process called type IV delayed hypersensitivity. This produces inflammation and tissue damage in a reaction termed allergic contact dermatitis.

Allergic contact dermatitis is different from irritant contact
dermatitis in that irritants damage the skin directly, while
allergens invoke an immune response that causes the
damage. The hapten, in the case of urushiol, penetrates and
is modified by Langerhan cells. The lymphocytes are
exposed to the modified urushiol + membrane protein and
initiate a response. The activated T cells then circulate and
react the next time the urushiol is touched.
As with other allergy reactions, contact dermatitis requires a sensitizing dose, in which your body is exposed to the allergen and ramps up a small reaction. Subsequent episodes are worse because part of the allergic reaction in the immune system sticks around (immune memory).

Not everyone’s immune system recognizes or overreacts to the hapten + membrane protein, so not everyone gets a rash from poison ivy – lucky devils! Other permutations are possible as well. You can be resistant and then develop an allergy late in life, or you can have contact dermatitis when young and later on become resistant. We know a lot about allergic hypersensitivity, but there's also a lot we don’t know. Much research is underway on plant toxins and allergens.

And herein lies the rub - pun intended - with many toxic plants. They cause pain, damage and irritation, yet Paracelsus said, “only the dose makes the poison.” Does that mean that a lower dose has no effect? Well, most of our medicines – antibiotics, anti-cancer, anti-depressive - come from fungi and plants. It isn’t just that less may not be harmful; less might actually be helpful!

Take urushiol for instance. A 2011 study shows that urushiol can kill H. pylori, the bacterium that causes many stomach ulcers. Within 10 minutes, urushiol can strip the membrane off of the bacterium and cause it to lyse. Traditional treatments were found to eradicate the disease in 75% of cases, but adding urushiol brought a 100% cure rate. It even worked in a mouse model, but no one asked the mice if their stomachs itched. Even hippomanin A is an inhibitor of herpes simplex virus 2 replication. It seems that every toxic plant we talk about here has some medicinal use – nothing and nobody are completely evil.

There are several plants that could wrestle for the title of most toxic, but anyone’s top five contenders would have to include oleander (Nerium oleander). You can die just from eating honey collected from bees that landed on the plant and partook of the pollen or nectar.

Nerium oleander is a bush like plant that can have red or
white flowers. It is deadly, but is repairing its reputation
by being used as a medicine. Oleander is the official flower
of Hiroshima, Japan, as it was the first flower that grew
after the atomic bomb was dropped. In Texas, oleander is
used as a decorative plant in road medians – don’t mess
with Texas medians!
The principal toxin is oleandrin, a cardiac glycoside. This type of toxin messes with the electrical impulse generation in heart muscle cells. As a result of the toxin, cardiac activity is dysfunctional, often to the point of arrythmia and heart attack. In other cells, it interferes with calcium levels and can induce cell death. Despite these evil tendencies, oleandrin is proving to be a very useful medicine.

A 2012 study has shown that oleander distillate is therapeutic in diabetes. Rats with induced diabetes were treated with oleander extracts for 12 weeks. Those treated rats had better blood sugar levels, reduced insulin resistance and cholesterol, and improved insulin levels. Not only was the diabetes positively affected, but fat levels were also positively affected – all through treatment with a lethal poison.

But wait - there’s more! Oleandrin has been show to be effective in inhibiting cancer. In at least five different kinds of cancer, oleandrin can stop cancer cells from increasing in number (proliferating), and can even induce the cancer cells to kill themselves (apoptosis). That’s a good start, but it gets better.

A 2005 review discusses the idea of resistance to treatment that develops in many cancers over time. Wouldn’t it be great if we had something that could make the cancer cells sensitive to the drug treatments again? Well, this review discusses studies that show oleandrin can do just that. Oleandrin acts not only as a chemosensitizer, but makes cancer cells more sensitive to radiation therapy. Therefore, oleander is synergistic with other cancer therapies and makes them work better.

Can you stand any more wondrous uses for this poison? A more recent study indicates that oleandrin reduces infectivity of HIV. AZT, a traditional HIV drug, reduces replication but not infectivity, while oleandrin reduces infectivity but not replication, so they could work together.  Oleander can save you from infectious diseases, cancers, and metabolic diseases – but eat the berries on your next hike and you’ll die a horrible death.

Both the cinnabar caterpillar (left) and the moth (right) are
brightly colored. This is called aposematism, warning predators
that they are toxic. It usually works, but the common cuckoo is
apparently opposed to aposematism; it has learned to avoid the
most toxic portions of the larvae and adult.
So humans are animals that can’t just willy-nilly start munching on toxic plants. But other animals can. We have talked about animals that use the toxins they eat (2˚ toxin sequestering), usually from either insects or plants. But is there an exception – does any animal sequester a toxin that its prey sequestered from a plant? I looked for one.

There is a cuckoo that eats the cinnabar moth caterpillar that eats toxic ragwort. The plant has alkaloids. In the stomachs of most animals, they are quickly converted to toxins. But a 2012 study shows that the cinnabar moth caterpillar’s enzymes can convert the metabolic products back to their non-toxic alkaloid forms. Then they are ready to poison the unwitting animal that eats the caterpillar and hasn’t had the forethought to evolve a detoxification process!

However, the common cuckoo (Cuculus canorus) avoids the toxins in the cinnabar caterpillar by biting off the head of the larvae and discarding it, then shaking the carcass to expel the liquid toxin. This is like how some birds can eat monarch butterflies. Monarchs are toxic, having sequestered milkweed toxins they ate as caterpillars. Shining cuckoos in New Zealand and some North American birds know to get rid of the most toxic portions and just eat the rest. Therefore, these birds are not 3˚ toxin sequesterers. I couldn’t find an example – can you?
The monarch caterpillar eats only milkweed – ONLY milkweed.
This is where is picks up its toxins. The adult will drink nectar
of many flowers, but the toxin is maintained as the larvae
metamorphed to the adult.

Most birds just stay away from monarchs most of the time, but even this has weirdness associated with it. Monarchs lose toxicity as they age, and males usually have less toxin than females, yet somehow the birds can sense it. Research has shown that monarchs with higher levels of toxin are less likely to be attacked by a predator. How do the birds know?

We have just touched the surface of toxic plants; there are more than we can mention. In Australia alone there are said to be over 1000 toxic plants! Let’s next look to our exceptions; plants that aren’t just toxic, they’re venomous.

Bas, A., Demirci, S., Yazihan, N., Uney, K., & Ermis Kaya, E. (2012). Nerium oleander Distillate Improves Fat and Glucose Metabolism in High-Fat Diet-Fed Streptozotocin-Induced Diabetic Rats International Journal of Endocrinology, 2012, 1-10 DOI: 10.1155/2012/947187

Suk, K., Baik, S., Kim, H., Park, S., Paeng, K., Uh, Y., Jang, I., Cho, M., Choi, E., Kim, M., & Ham, Y. (2011). Antibacterial Effects of the Urushiol Component in the Sap of the Lacquer Tree (Rhus verniciflua Stokes) on Helicobacter pylori Helicobacter, 16 (6), 434-443 DOI: 10.1111/j.1523-5378.2011.00864.x

Garg, A., Buchholz, T., & Aggarwal, B. (2005). Chemosensitization and Radiosensitization of Tumors by Plant Polyphenols Antioxidants & Redox Signaling, 7 (11-12), 1630-1647 DOI: 10.1089/ars.2005.7.1630

For more information, see:

Plant toxins –

Wednesday, April 17, 2013

It’s An All Or None Proposition

Biology concepts – toxin, venom, cnidarians, kleptocnidae

In our discussions of venoms and toxins we have looked at many groups (phylums) of animals. In each phylum we have identified at least one venomous animal. We have talked venomous amphibians (frogs, salamanders), venomous reptiles (lizards, snakes), venomous arthropods (insects and spiders), and even venomous mammals. Even though we haven’t talked about them in this series, there are also venomous sponges, and sponges are the most primitive animals on Earth.

Sinornithosaurus was a raptor dinosaur with feathers;
a very early proto-bird. It was still a reptile, but with
features that would come to be typical of birds. One
thing that wasn’t typical was its teeth. A 2009 study
indicated that one of its long fangs had a groove down
the side – channel for venom! So, while no modern birds
are/were venomous, maybe an ancient ancestor was.
If even the most primitive animal phylum has members that are venomous, then all phylums probably do – right? Well, no – birds are the exception. We know of no venomous bird; NO bird makes or sequesters a toxin that is then delivered by bite or talon scratch or other natural mechanism.

Birds are the evolutionary descendents of the reptiles; they diverged from the reptiles about 240 million years ago. The toxicofera hypothesis says that all reptiles were at one time venomous, so why aren’t the birds? It may have something to do with the timing of the divergence. The oldest venom genes and delivery systems are associated with the lizards, about 200 million years ago, AFTER the divergence of birds. Mystery solved. Of course, mammals and arthropods had diverged hundreds of million years earlier, and they have some venomous species. If they could do it on their own, why couldn’t birds?

Well, a few birds have found a way to use the toxins produced by other organisms. Members of the pitohui family of birds in Papua New Guinea tend to feed on toxin producing choresine melyrid beetles.  The toxins remain in the bird’s tissues and feathers for some time before they are broken down or excreted.

Just rubbing against the feathers can induce numbing, and consuming a bird would be lethal for many animals, including humans. The Hooded Pitohui seems to know this and is very social and loud. It suspects that predators know it is a bad meal and will leave it alone. An added benefit - lice that usually live in the feathers are also affected by the toxin, so these birds are relatively parasite-free.

This is the spur winged goose. It lives in the wetlands
of Saharan Africa. It also feeds on toxic insects, so it
comes by its toxins in the same way that the pitohuis
do in New Guinea. Not all the geese are toxic, since
they have a large range. Only some live near the
blister beetles of Gambia that are poisonous and
render the birds toxic.
This is odd, since the toxins involved are from the batrachotoxin family, just about the most potent neurotoxins on the planet. They work by binding to the ion channels in neurons and holding them open. This prevents the neuron from recovering after it sends an electrical signal. Therefore, the neuron can’t fire anymore, and whatever it is connected to can't be stimulated. If it is connected to a touch receptor, you will feel numb there. If it is connected to a muscle, the muscle will be paralyzed. Batrachotoxins seem to work in every animal that has this type of neural system, so why isn’t the beetle the bird’s last meal?

Birds are certainly an exception to the rule that at least some organisms in each phylum developed venom. How about the other end of the spectrum? It would also be an exception if we had a phylum of animals that were ALL venomous. Well, we do.

The cnidarians are the phylum of animals that include the anthozoans (corals and sea anemones), and the medusozoa (jellyfish, box jellyfish, and the hydras). It turns out that EVERY species of cnidarian is venomous, though some might not be venomous enough to harm humans.

Cnidarians all have cnidocytes (cnida = nettle, like plant nettles that stick you and cyte = cell); cnidocytes are the secret handshake required for membership in the cnidarian club. There are three main flavors of cnidocytes; nematocysts, spirocysts, and ptychocysts. It is the nematocysts that make cnidarians venomous.

Nematocytes are the cells that house the actual stinging apparatus, called nematocysts. They have a barbed shaft that together looks like a harpoon end. This is housed in a cavity filled with venom and covered by a trap door (operculum). There are about 35-40 different shapes and lengths for nematocysts, but they all work basically the same way.

The left image is a cartoon of a typical cnidarian nematocyte. You
can see the operculum, the trap door on top, as well as how the
barb is packaged inside the cnida. The entire volume is filled with
venom that is sprayed out under pressure when it fires. The right
image is a photomicrograph of a fired nematocyst. The scale
shows how small they really are ( a micron - ┬Ám - is a millionth
of a meter).
When triggered by mechanical pressure on a hair cell sticking out, and sometimes when accompanied by a chemical signal that a prey organism is near (they “taste” the water), the pressure inside is increased, reaching more than 2000 pounds per square inch, and the cell bursts. 

The operculum opens and the shaft is everted at the prey in just 700 nanoseconds (about 700 billionths of a second), with an acceleration of more than 5,400,000 x gravity. It isn’t a surprise that the prey’s skin is pierced by the shaft! The pressurized venom is then injected into the wound through the hollow shaft and/or hollow tubule.

For some cnidarians, like the sea wasp (Chironex) or the Portuguese man-of-war (Physalia), the venom is important because their prey is strong, including large fish. Most cnidarians, especially jellyfish, are fragile animals; they don’t have a strong internal skeletal and can be ripped apart easily. Therefore, it is important for them to immobilize their prey quickly. The venom does the job. It works very well, for some jellyfish it works well enough to severely harm (Irukandji jellyfish) or kill (sea wasp) humans.
Inside the vial is an Irukandji jellyfish. It is small, but it
packs a wallop. This is one of the few jellyfish that
possess nematocysts on its bell (the round part at top) as
well as on its tentacles. The lower image shows that
while the body s about 5 mm long, the tentacles of the
Irukandji jellyfish can be up to a meter long! One, you can
hardly see it, and two, it can nail you from long distance.

Spriocysts and ptychocysts are the other types of cnidocytes. I was worried about making the statement that all cnidarians are venomous, on the off chance that some cnidarians possess only spirocysts and/or ptychocysts. I contacted several researchers that study cnidarians, and they all stated that as far as they know, all cnidarians possess nematocysts, while only some have spirocysts and/or ptychocysts.

Many cnidarians rely primarily on spirocysts. These cnidocytes are very similar to nematocysts, except that they don’t have an associated venom. Spirocysts are used primarily by cnidarians that prey on less vigorous animals, animals that aren’t as able to pull them apart at the seams. Most corals, for example, prey on small invertebrates, so they rely less on venom and more on entanglement. This is the function of spirocysts, they substitute adhesive for venom.

The bubble tip anemone (Entacmaea quadricolor), for example, relies on a combination of nematocysts and spirocysts to bring in its prey and for defense. But it doesn’t have to hunt much to gather food. It has symbiotic relationships with other animals that help out. The bubble tip is often green colored, because it has intracellular photosynthetic dinoflagellate organisms that provide it with carbohydrates.

The bubble tip also has a relationship with the clownfish (think Finding Nemo). The fish clean away parasites and devour any dead tentacles, while they also scare off predators and provide the anemone with scraps from its meals. Though the bubble tip does have nematocysts, it seems that the clownfish is immune to the toxin, so living amongst the tentacles provides the clownfish with protection from its predators.

Entacmaea quadricolor is the scientific name for the bubble
tip anemone. It comes in four different colored varieties,
pink, red, orange, and green – hence the name “quadricolor.”
And the “Nemo” fish it protects is actually called a
cinnamon anemonefish. I’m wondering who decided
it tasted like cinnamon. Sometimes it is called a fire
clownfish – so does it taste like fire too?
The third class of cnidocytes are the ptychocysts. These are restricted to a group of sea anemones called tube anemones. They are used to build the tubes that these animals live inside. The threads of the ptychocysts are mixed with mucus and debris and become fibrous houses for the animals inside. As such, they are mainly for defense, not for catching food. Yet they do have nematocysts for defense as well.

Some people think that there are some cnidarians that have lost the ability to sting using nematocysts. The TV show, Survivor, went to Palau for a season, including an episode where the winners of some challenge were rewarded with a chance to swim in the lakes with the jellyfish. These golden jellyfish and moon jellyfish are related to the species that live in the nearby ocean, have been separated geographically for thousands of years.

This separation has led to the misconception that they have lost their nematocysts due to a lack of predators. But it is not so, moon jellyfish stings in the lake will be noticed, just not as much as those fro the ocean. Perhaps a genetic drift is taking place, but swimmers do report numbness around their mouths and fingers, so the jellyfish in the lake do still have venom.

Venom from cnidarians protects cnidarians, but it also protects others. Nudibranches are a type of sea slug, related to snails and other molluscs. They eat cnidarians, but not only do they eat them, they use them as well. The use of cnidarian nematocysts by nudibranches is discussed in a 2009 review by Paul Greenwood. 

Berghia coerulescens likes to eat sea anemones; it may or may not be susceptible to the venom. But that doesn’t really matter since the nudibranch eats the nematocytes whole, perhaps without triggering them to fire.

Nudibranch sea slugs are some of the most colorful
animals in the world. You can see the cerata on its back,
like so many dreadlocks. These are where the
nematocysts are housed for defense. They should make
a Disney movie about a sea slug – Where’s Nudi?
There are two hypotheses as to how B. coerulescens can consume the nematocytes and then place them into its cerata on its back. One hypothesis is that they coat them with mucus and that keeps them from firing as they are eaten and moved through the digestive system. The other hypothesis states that they mature nematocytes do discharge, but the immature nematocytes cannot; they are then sequestered and mature while being it held in the cerata.

Either way it occurs, when the nudibranch is threatened, it stiffens its cerata and the musculature moves the nematocytes to a pore. When they contact the seawater, they fire. This is supposed to keep the predators at bay. The review of Greenwood discusses whether this defense is effective – maybe, maybe not. It needs more study.

We just scraped the surface of the weirdness that is the cnidarians, so we will talk more about them in the future. However, next week we will finish the stories on venoms and toxins by looking at the poisonous plants. Did I say, poisonous? Well at least one is venomous.

Gong, E., Martin, L., Burnham, D., & Falk, A. (2009). From the Cover: The birdlike raptor Sinornithosaurus was venomous Proceedings of the National Academy of Sciences, 107 (2), 766-768 DOI: 10.1073/pnas.0912360107

Greenwood, P. (2009). Acquisition and use of nematocysts by cnidarian predators Toxicon, 54 (8), 1065-1070 DOI: 10.1016/j.toxicon.2009.02.029

For more information or classroom activities, see:

Cnidarians –

Nematocysts –

Sinornithosaurus –

Toxic birds –

Kleptocnidae -

Wednesday, April 10, 2013

Sneaky Snakes: Biters, Boobytraps, and Spit

Biology concepts – venom, toxin, poison, fangs, evolution, toxicofera hypothesis

The California Red Sided Garter Snake is one beautiful
reptile.  It has round pupils, so it might be non-venomous,
but it has a highly patterned and bright colored body, so
it could be poisonous. It has a triangular head, but not to
broad, so it could be either. For many years we thought
it was non-venomous, but recent work says it has toxic
saliva. It’s probably not too harmful to humans, but it
goes to show that you can’t make assumptions.
If you know anything about this blog, you know that we look for exceptions in every rule, so I wouldn’t tell you that there are definitive ways to tell venomous from non-venomous snakes. There are just too many exceptions; any mistake in this area could be your last.

However, many people will tell you that the eyes of a snake will give them away –round pupils means non-venomous, while slit pupils (like cats) means venomous. Or that venomous snakes have patterned bodies while non-venomous snakes wear solid colors. Lastly, some people will tell you that venomous snakes have triangular heads, while non-venomous snakes have rounder heads.

Let’s tear down each myth. About 99% of snakes have triangular heads. So this is no help at all; although, if you stay away from all triangular headed snakes you probably won’t get in trouble. Venomous snakes do have a broader base to their triangular head, to account for the venom gland volume and associated muscles. However, are you going to take the time to determine just HOW BROAD is the head of the snake that’s about to bite you?

As for pattern versus solid color; this will also fail you. Ever hear of a black mamba (Dendroaspis polylepis)? Well, it’s the most venomous snake in Africa and it’s solid colored. Strangely enough, the black mamba isn’t black. Its name comes from the color of the inside of its mouth, but its body is silvery. The Inland Taipan viper (Fierce Snake, Oxyuranus microlepidotus) is the most venomous on land, but it has a solid dark tan body.

Maybe pupil shape matters. I am wondering why there would be an evolutionary link between the shape of the pupil and whether a snake has venom. Head shape – maybe, you have to account for venom glands. Body color – maybe, patterns would warn a predator to stay away (aposematism). But pupil shape? How would that be linked to venom or no venom?

The black mamba is one of the most aggressive of venomous
snakes. It’s as if it goes out looking for things to bite. And
they are fast, moving up to 20 ft./sec (that’s 14 mph, or 22.5
kph), although I think Kobe Bryant can still move faster than
that in short spurts. The mamba grows to over 10 ft in length
and will attack a lion, so it backs up the deadly look of its
open mouth – it ain’t just for show.
We can use the black mamba and inland taipan snake examples for debunking the pupil myth as well. The mambas and the fierce snake are round, as are the pupils of the coral snake (very dangerous). More to the point, who wants to get close enough to a snake’s pupils to see if they are slit shaped or round? Let’s err on the side of caution; if you see a snake in the wild – assume it’s venomous. Problem solved.

So let’s find some real exceptions in the realm of venomous snakes. Unfortunately, there are so many different combinations of fang type, venom type, and venom gland type that it is difficult to call any kind of venomous snake an exception – there aren’t many rules. There are true venom glands and false glands, based on whether they can store venom. Then there are rear fangs, front fangs, and front fangs that can fold up. And then there are systems that deliver venom to several upper teeth, and those that deliver venom only through the channels in front fangs or rear fangs.

There may be different ways to deliver and different venoms to deliver, but a 2008 study says it all venomous snakes derive from a common ancestor that lived about 60 million years ago. The study of Dr. Vonk looked at front and rear-fanged venomous snake embryos, and saw that the venom gland ducts ALWAYS start out attached to a rear tooth, but in the front-fanged snakes, the tooth and duct move forward during fetal development!

The rear-fanged snakes have back teeth that deliver venom,
but not by injecting it like a hypodermic. They are not hollow;
some have grooves for the venom to run down, while others
are just sharp, bigger teeth. Snakes with rear fangs have to
take a bigger bite, and hold on longer to grind the venom into
the wound. Doesn’t sound like the perfect system, but
evolution is striving for perfection, it just uses what is there.
What is more, it would seem that the tooth that developed into a fang became linked to the development of the venom gland rather than the other teeth, suggesting that they co-evolved in all types of venomous snakes, linking the type of venom with the type of delivery and type of fang. Perhaps they all started out the same, but they developed their own combinations independently.

It may be that this occurred with all snakes; those that aren’t venomous just lost the ability to produce or deliver venom. This is part of the toxicofera hypothesis of which we have spoken. We don’t even know what percentage of snakes are venomous. Scientists have focused on the highly venomous snakes for so long, that the so-called non-venomous snakes have been ignored.

Many snakes that were once thought to be non-venomous are now known to have venomous bites. Colubridae snakes (garter snakes, hognose snakes and many more) were thought up to the 1950’s to be utterly non-venomous. But Dr. Fry showed that many of these snakes do indeed deliver venom, though most may be harmless to humans.

As recently as ten years ago it was said that only 10% of snakes were venomous; now that percentage is somewhere near 30%. Where might it end – could most snakes be venomous?

Even though scientists now know more about the evolution of venom, there are still mysteries. With millions of years to perfect a venom system, why is it that some snakes have venom that is WAY TOO POTENT for its purpose? With each bite the fierce snake delivers enough venom to kill 2000 mice or 50 humans – why so much? It must be advantageous in some way; or else it doesn’t cost any more energy to make the venom that potent.

This is a juvenile tiger keelback snake. The raised part on the
back explains the name. It is actually the nuchal gland that
stores cane toad toxin as a defense. How could a small
juvenile have toxin before it is big enough to start eating cane
toads? It can be passed on from mother to offspring, if she
ate a cane toad before egg format
Great diversity in venoms and fangs aside, there are exceptions in venomous snakes. Let’s talk about the keelback snakes. They may be venomous, but they are also poisonous.

Debra Hutchinson published on the keelback snakes in 2007. Tiger keelback snakes (Rhabdophis tigranus) live in Asia, and enjoy a diet of cane toads – poisonous cane toads! Cane toads kill most things that try to eat them, but for some reason the keelback snakes don’t seem to be bothered by the toxin.

In fact, they sequester the cane toad toxin to two nuchal glands, located on the back of their necks. Then, when the snake is threatened by a predator, they turn their back to the aggressor and dare them to bite down on the nuchal glands! Most predators have learned not to take the bait.

The nuchal glands are purely for storage. They don’t have ducts or deliver the poison to the skin or a fang. The sequestered toxin is purely defensive. But the keelbacks also have venom glands, of the false gland type, delivered to the base of several upper teeth. The keelback then bites, chews and grinds the venom into the wound.

This is the way it goes for many rear fanged snakes. Delivering venom by the front fangs is 100x more efficient than the rear fangs, so rear fang snakes must hang on longer to their target in order to envenomate them. This means that they are more vulnerable to being bitten when the target fights back. The keelback has made this less likely by storing another toxin in its neck. Pretty smart, huh?

When threatened, the tiger keelback assumes a familiar neck
arch position. This was described in Akira Mori’s 2012 paper.
If disturbed, it will also try to bump the nuchal glands into the
aggressor, They will spray toxic contents if bitten or pinched.
Now for one more venomous snake exception. Your parents always told you not to spit, but a few snakes are expectorating geniuses. The spitting cobras (genus Naja, and a couple others) have an additional modification to their front fangs that gives them the ability to spit their venom, in some cases, over twenty feet.

Injecting venom from front fangs is controlled by specific muscles around the venom gland. Spitting snakes combine this quick delivery under pressure with a targeting system. Instead delivering venom from the tips of their fangs, they have an aperture (hole) in the front face of their fang (see picture). Some cobras aim for the eyes of their targets, while others aim for mouth, nose or skin.

The aim is incredible in all, but it is even better in some species. I will use guns as a model. Most guns and cannons up to the time of the US Civil War were very inaccurate. By gouging curved grooves down the barrel, a spin was placed on the cannon ball, and the spin made it much more accurate. This “rifling” was invented in the 1500’s, but didn’t become common until the 1800’s.

The same is seen in the African (not so often in the Asian) spitting cobras. The fang and aperture have rifling grooves that make them even more accurate. I would say that humans stole the idea from nature (like we so often do), but I don’t think we knew about spitting cobras when guns barrels started being rifled.

But how does spitting (really squirting, no saliva is involved) venom at an aggressor help, other than grossing them out? We know that venom must be injected below the skin in order to be effective, but a spitting cobra’s toxin can be cytotoxic (lots of inflammation and tissue destruction) to the skin, and can blind if it hits the eyes. The black-necked cobra and the red Mozambique cobra have been shown to aim only for eyes.

This is a Mozambique spitting cobra. Notice how the spray
comes straight out from the front of the fangs and is directed in a
narrow, pointed direction. This isn’t strafing fire, it’s sniper work.
In a 2005 study of spitting cobras, the red and black-necked spitters recognized faces and eyes, but would not spit at photographs of faces. That’s mighty evolved; you don’t want to waste the toxin, and you must be accurate to avoid waste as well. The black-necked was able to hit the eyes 80% of the time, and the red spitter never missed.

Most spitting cobras actually have a mix of toxins; some neurotoxic, some hemotoxic, some cardiotoxic, and some cytotoxic. Somewhere along the way, evolutionarily speaking, the spitting cobras concocted a toxin that has both the ability to harm by surface contact, and the ability to harm on contact. Evolution at its best.

Next week, is there a group of animals where every species is venomous? And how about a group where none of the species are venomous.

Vonk, F., Admiraal, J., Jackson, K., Reshef, R., de Bakker, M., Vanderschoot, K., van den Berge, I., van Atten, M., Burgerhout, E., Beck, A., Mirtschin, P., Kochva, E., Witte, F., Fry, B., Woods, A., & Richardson, M. (2008). Evolutionary origin and development of snake fangs Nature, 454 (7204), 630-633 DOI: 10.1038/nature07178

Mori, A., Burghardt, G., Savitzky, A., Roberts, K., Hutchinson, D., & Goris, R. (2011). Nuchal glands: a novel defensive system in snakes Chemoecology, 22 (3), 187-198 DOI: 10.1007/s00049-011-0086-2
Hutchinson, D., Mori, A., Savitzky, A., Burghardt, G., Wu, X., Meinwald, J., & Schroeder, F. (2007). From the Cover: Dietary sequestration of defensive steroids in nuchal glands of the Asian snake Rhabdophis tigrinus Proceedings of the National Academy of Sciences, 104 (7), 2265-2270 DOI: 10.1073/pnas.0610785104


For more information and classroom activities, see:

Snakes –

keelback snakes and nuchal glands –

spitting cobras –