December 22, 2009
Whatever Doesn't Kill Some Animals Can Make Them Deadly
By SEAN B. CARROLL
Have you ever tried to think up the worst meal you could imagine? How
about blue-ringed octopus, floral egg crab, basket shell snails and
Sure, some people may think these are delicacies, and puffer fish is
certainly treated as such in parts of Asia. But each dish has
something more important in common: they are all deadly. Each of these
animals is chock full of a powerful neurotoxin called tetrodotoxin.
First isolated from the puffer fish, tetrodotoxin is among the most
potent toxins known. It is 100 times as toxic by weight as potassium
cyanide — two milligrams can kill an adult human — and it is not
destroyed by cooking. Just half an ounce of the fish liver, known as
fugu kimo in Japan and eaten by daring connoisseurs, can be lethal.
When ingested, the toxin paralyzes nerves and muscles, which leads to
respiratory failure and, in some cases each year, death.
In 1975, the Kabuki actor Bando Mitsugoro VIII ordered four fugu kimo
in a restaurant in Kyoto, claiming he could resist the poison. He was
Tetrodotoxin is found in more than just marine creatures. It is
present in high concentrations in the skin of certain newts in North
America and Japan, and in several kinds of frogs in Central and South
America and Bangladesh. The widespread occurrence of tetrodotoxin
poses some intriguing riddles. First, how is it that such different
animals, belonging to separate branches of the animal kingdom, have
all come to possess the same deadly poison? And how is it that they
are able to tolerate high levels of tetrodotoxin while others cannot?
The questions are particularly interesting because, in general, animal
toxins are distinct and specific to each group. For instance, the
venoms produced by snakes and scorpions are made of different kinds of
toxins. But the tetrodotoxin found in each dish of that deadly buffet
One explanation could be that each of these animals has independently
found a way to synthesize tetrodotoxin. But the toxin is a rather
complex molecule that requires several chemical steps to assemble. It
seems very unlikely that the molecule would be invented many times
over in different animals. Rather, the evidence suggests that animals
do not make the toxin themselves.
For instance, when puffer fish are raised in aquariums with filtered,
bacteria-free water, they are nontoxic. Similarly, when Japanese newts
or Panamanian frogs are raised on special diets, they lose their
toxicity. These experiments indicate that tetrodotoxin-bearing animals
obtain the toxin from the food chain. Indeed, several species of
tetrodotoxin-producing bacteria have now been isolated from puffer
fish, the blue-ringed octopus, certain snails and other animals. It
appears that the animals become toxic by sequestering the bacterially
produced toxin in their tissues.
While those discoveries solve the mystery of the source of
tetrodotoxin, they do not quite explain how so many kinds of animals
exploit it. Tetrodotoxin attacks an ancient feature of the animal
kingdom, blocking channels that normally control the movement of
sodium ions across nerve and muscle cell membranes and halting their
electrical activity. All animals have these sodium ion channels, and
the part of the channel that tetrodotoxin fits into and blocks is
generally very similar among them.
This fact raises a simple question: Why aren't puffer fish dead? How
are tetrodotoxin-bearing animals able to withstand high levels of a
substance that attacks their nervous systems?
One clue is that not all 120 or so species of puffer fish are toxic or
resistant to tetrodotoxin. Toxic species can withstand about 500 to
1,000 times the concentration of tetrodotoxin compared with nontoxic
puffers or other fish. The flower egg crab is similarly resistant, and
the Japanese newt can withstand an even greater relative concentration
of toxin. Most other crabs and newts are sensitive to tetrodotoxin.
There must be something different then about toxic,
That difference becomes clear from examining their sodium channels in
detail. Puffer fish have eight versions of these channels encoded by
eight separate genes. Manda Clair Jost and her colleagues at the
University of Texas at Austin and the University of Chicago have
discovered that in toxic puffer fish, most or all of these channels
have evolved resistance to tetrodotoxin and different groups of puffer
fish appear to have independently acquired resistance. Toxin-resistant
channels have also been identified in a Japanese newt.
So the most plausible chain of events for the evolution of high-level
toxin resistance is that mutations initially occur that afford some
protection and that the continuing presence of tetrodotoxin in the
environment selects for animals bearing additional mutations until,
over time, many or all channels are highly resistant. In this sense,
what does not kill the evolving animals makes them stronger, and
In most cases, tetrodotoxin is an effective defensive weapon. But in
the game of natural selection, victory is rarely total or permanent.
Predators could evolve resistance via the same path that made prey
toxic, and this is exactly what has happened in some snakes in the
western United States that now feast on highly toxic newts.
Unlike most snakes that are immobilized, sickened or killed when they
try to ingest these newts, members of three species of garter snakes
are able to dine on the toxic amphibians. A team of researchers led by
Edmund Brodie Jr. of Utah State University and his son Edmund Brodie
III of the University of Virginia found that the species have
independently evolved tetrodotoxin-resistant sodium channels. Indeed,
some snakes from California are so resistant that the dose of toxin
needed to immobilize them is sufficient to kill 900 people.
Remarkably, some of the same channel gene mutations responsible for
conferring partial resistance to tetrodotoxin have occurred in
different snake species. Moreover, some of these and other mutations
have also occurred repeatedly in puffer fish channels.
These precise parallels in channel evolution among species reveal a
surprising facet of evolution that biologists had no inkling of before
the ability to pinpoint adaptive changes in DNA — namely, that
evolution is more reproducible than previously thought. The simple
explanation for that profound insight is that given similar agents of
natural selection (tetrodotoxin in this case), very different species
living in different places on the planet will evolve similar or
It follows then that evolution is somewhat predictable. Given the
prevalence of tetrodotoxin-producing bacteria and the many known uses
of the toxin as a defensive weapon strategy, we should expect to find
more toxic animal species.
With luck, the discoveries will not be made at dinner.
Sean B. Carroll, a molecular biologist and geneticist, is the author
of "Remarkable Creatures: Epic Adventures in the Search for the Origin
On 10/27/09, roger malina <firstname.lastname@example.org> wrote:
> see DARWIN'S ROBOTS project
> Subject: Sarah Jane Pell sent you a message on Facebook...
> Subject: Latest Articles | h+ Magazine
> "Darwin's Robots for the Yasmin discussion.
> Kind regards, Sarah Jane"
> Sarah has shared a link with you. To view it or to reply to the message,
> follow this link:
> Roger Malina is in France at this time
> IN USA
> phone 1 510 853 2007
> When in France I can be reached at:
> 011 33 (0) 6 15 79 59 26
> or (0) 6 80 45 94 47
> Yasmin_discussions mailing list
> Yasmin URL: http://www.media.uoa.gr/yasmin
> HOW TO SUBSCRIBE: click on the link to the list you wish to subscribe to. In
> the page that will appear ("info page"), enter e-mail address, name, and
> password in the fields found further down the page.
> HOW TO UNSUBSCRIBE: on the info page, scroll all the way down and enter your
> e-mail address in the last field. Enter password if asked. Click on the
> unsubscribe button on the page that will appear ("options page").
> HOW TO ENABLE / DISABLE DIGEST MODE: in the options page, find the "Set
> Digest Mode" option and set it to either on or off.
Yasmin_discussions mailing list
Yasmin URL: http://www.media.uoa.gr/yasmin
HOW TO SUBSCRIBE: click on the link to the list you wish to subscribe to. In the page that will appear ("info page"), enter e-mail address, name, and password in the fields found further down the page.
HOW TO UNSUBSCRIBE: on the info page, scroll all the way down and enter your e-mail address in the last field. Enter password if asked. Click on the unsubscribe button on the page that will appear ("options page").
HOW TO ENABLE / DISABLE DIGEST MODE: in the options page, find the "Set Digest Mode" option and set it to either on or off.