Venomous Snails • iBiology

00:00:05.06 Hi, I am Toto Olivera.
00:00:08.22 I am a professor at the
00:00:11.01 University of Utah.
00:00:12.10 And I would like to tell you about
00:00:13.23 venomous cone snails.
00:00:15.08 So, you've heard about predators.
00:00:19.24 And it is seldom
00:00:21.23 that you
00:00:22.03 think of a snail
00:00:23.01 as a predator.
00:00:23.24 You think of snails
00:00:24.23 that are crawling around
00:00:25.14 in your garden.
00:00:27.11 But I am going tell
00:00:28.15 you about a special group
00:00:29.24 of snails called cone snails.
00:00:31.27 And they are predators.
00:00:33.15 And predators vary
00:00:35.11 from those that use
00:00:36.21 mechanical strategies
00:00:38.27 such as a great white shark.
00:00:40.23 You have to be able to swim fast
00:00:42.25 and have great teeth
00:00:44.04 if you are a white shark.
00:00:45.10 To predators that have
00:00:48.08 a mixed mechanical
00:00:49.22 and chemical strategy
00:00:50.23 such as the Komodo dragon,
00:00:52.16 which has very strong jaws
00:00:54.15 but nevertheless it
00:00:56.07 has secretions that allow
00:00:57.29 it to help capture its prey.
00:01:00.04 To the cone snails, which are
00:01:02.10 in fact predators as well,
00:01:04.16 but they use
00:01:05.14 a purely chemical strategy,
00:01:07.16 and that makes them
00:01:08.23 fairly unique as predators.
00:01:10.24 So there are 700 different
00:01:14.09 types of cone snail species,
00:01:17.09 and all of them
00:01:18.17 are predatory.
00:01:19.22 All of them are
00:01:20.15 venomous. And each species
00:01:23.04 has fairly specific prey.
00:01:26.06 Some cone snails prey on fish.
00:01:28.17 Some cone snails
00:01:30.14 prey on marine worms.
00:01:32.01 And some cone snails
00:01:34.01 prey on other snails.
00:01:35.13 All of them live
00:01:36.21 in the tropics,
00:01:37.23 in the oceans
00:01:39.19 from very shallow water
00:01:42.05 to really deep water.
00:01:43.04 And the most unusual
00:01:46.17 kinds of snails
00:01:48.18 are those that hunt fish
00:01:50.29 becuase they not only
00:01:52.11 are successful hunters of fish,
00:01:54.12 but a few species
00:01:56.15 are dangerous to man
00:01:58.09 and can kill people.
00:01:59.07 And Conus geographus
00:02:01.21 which is the snail in the
00:02:02.19 center, the large snail
00:02:04.00 in the center,
00:02:04.03 kills people
00:02:06.15 with a 70% fatality rate.
00:02:08.27 So if you get stung
00:02:09.29 by this snail
00:02:11.05 and you have no medical attention,
00:02:13.21 you have a 70%
00:02:15.05 probablility of dying.
00:02:16.24 Let me show you
00:02:18.26 what the cone snails
00:02:20.02 do to catch fish.
00:02:21.29 So when a cone snail
00:02:23.04 sniffs a fish,
00:02:24.17 it extends
00:02:25.10 its distensible proboscis
00:02:26.16 as you see here,
00:02:28.26 and this particlular species
00:02:31.03 goes for a region
00:02:33.23 of the fish
00:02:34.12 called the lateral line
00:02:35.26 which is lots of nerves,
00:02:37.08 and what you can see
00:02:38.27 is the snail
00:02:40.11 beginning to
00:02:42.12 approach the fish,
00:02:44.01 and when it touches
00:02:44.13 the skin of a fish
00:02:45.23 then from the proboscis
00:02:47.08 out comes a harpoon like tooth
00:02:50.26 which is both harpoon
00:02:52.14 and hypodermic needle.
00:02:53.22 And so what you see
00:02:55.20 is the tooth extended,
00:02:57.20 and the venom flows from
00:02:59.03 the proboscis
00:03:00.00 to the tooth
00:03:01.06 and at the end of the tooth
00:03:03.03 is a hole
00:03:04.25 because it's hollow,
00:03:06.19 and so when this tooth
00:03:08.00 gets injected into a fish
00:03:10.02 the venom flows
00:03:10.28 into the body of the fish
00:03:12.16 and at the same time
00:03:13.14 it is speared,
00:03:14.18 because in fact the end of the tooth
00:03:16.11 is shaped like a harpoon.
00:03:19.13 So once the snail
00:03:22.14 touches the skin of a fish
00:03:24.07 it then can inject its venom,
00:03:27.13 and the effects
00:03:28.20 are what you are going to see here.
00:03:30.10 It tethers the fish,
00:03:32.19 and now it can
00:03:34.13 draw the fish into
00:03:35.14 its false mouth,
00:03:36.15 and in this case
00:03:38.02 in about an hour and a half
00:03:39.26 it will regurgitate
00:03:41.19 the scales and bones
00:03:42.28 of the fish
00:03:43.23 as well as the one
00:03:45.24 harpoon that it used
00:03:47.24 for injecting the venom
00:03:49.05 into the fish.
00:03:50.24 And so what you can see is
00:03:52.03 the fish
00:03:52.18 is immobilized
00:03:53.15 and now the snail
00:03:56.11 can completely
00:03:57.20 engulf the fish
00:03:58.14 in this false mouth
00:04:01.16 and predigestion
00:04:03.19 takes place
00:04:04.28 so that all the hard
00:04:06.02 parts get regurgitated
00:04:08.08 but the soft parts
00:04:09.12 of the fish go further down
00:04:11.00 into the digestive tract.
00:04:13.12 And what you can see
00:04:14.24 is that the
00:04:15.24 fish has very, very stiff fins
00:04:18.22 and that is one of the
00:04:19.21 effects of the venom
00:04:21.03 to cause this
00:04:22.21 so-called tetanic paralysis.
00:04:25.09 All cone snails
00:04:27.14 have the same
00:04:28.16 venom apparatus.
00:04:29.14 They have an organ
00:04:31.24 filled with harpoons
00:04:33.05 that are in various
00:04:34.04 stages of assembly
00:04:35.13 which is a quiverlike organ,
00:04:37.10 and when they go hunting
00:04:38.13 they move one
00:04:40.07 of the harpoons
00:04:41.08 to the tip of
00:04:42.02 their proboscis
00:04:42.15 and they use it
00:04:43.27 only once.
00:04:45.02 And the venom is actually
00:04:46.00 made in this long duct
00:04:47.14 and it is pushed out
00:04:49.09 by the muscular bulb
00:04:50.21 and as a result
00:04:52.13 this is an efficient way
00:04:54.00 to inject venom
00:04:55.01 into the prey.
00:04:56.18 So the snails
00:04:57.27 in effect
00:04:59.01 have evolved the
00:05:01.15 equivalent of disposable
00:05:03.09 hypodermic needles
00:05:04.01 for injecting
00:05:05.17 their venom into their prey.
00:05:08.04 Here is another snail
00:05:09.14 that is hunting
00:05:11.11 snails instead of fish.
00:05:14.16 And it is going to
00:05:15.06 inject its venom,
00:05:16.04 and when it injects
00:05:17.23 its venom,
00:05:18.12 you can see that the
00:05:19.08 behavior of the prey
00:05:20.12 snail changes
00:05:21.15 immediately.
00:05:23.19 And so because
00:05:25.00 the venom has this
00:05:26.09 effect on the snail,
00:05:27.09 the snail can't
00:05:28.18 move away,
00:05:29.06 and at the same time
00:05:30.18 it can't go into its shell.
00:05:31.29 And so now the predator
00:05:33.25 can eat it at its leisure.
00:05:36.00 What is interesting
00:05:36.19 about snail hunting cones
00:05:38.13 is they usually
00:05:38.28 have to harpoon
00:05:40.12 their prey many times
00:05:42.16 and that is so that
00:05:43.21 the muscles that
00:05:44.24 attach the snail
00:05:45.25 to the shell
00:05:46.28 become relaxed
00:05:48.18 and its easier
00:05:48.28 to pick out the snail.
00:05:50.25 This shows you
00:05:52.07 a video that really
00:05:53.27 shows how
00:05:54.25 fast the immoblization
00:05:56.07 can be with a good strike.
00:05:58.11 And this is real time.
00:05:59.23 And you can see
00:06:00.13 the fish is instantly
00:06:02.06 immobilized.
00:06:03.26 And this also shows you
00:06:07.02 an interesting thing
00:06:07.25 that was completely
00:06:08.22 unexpected.
00:06:09.22 As the snail begins
00:06:11.13 to engulf the fish
00:06:12.22 what you are going to
00:06:13.24 see is that
00:06:14.24 the fish in fact recovers
00:06:16.17 and so sometimes
00:06:19.13 the venom is effective,
00:06:23.12 but there are lapses.
00:06:25.16 And so you see
00:06:26.14 the fish recovers there.
00:06:28.00 In this case of course,
00:06:28.27 there is no biological effect
00:06:30.17 because the snail
00:06:32.12 has already completely
00:06:33.13 engulfed the fish.
00:06:34.12 But once in awhile,
00:06:35.11 you see these fish escape.
00:06:37.07 And under those conditions
00:06:38.29 the snail always does a search
00:06:41.17 for the paralyzed fish.
00:06:43.04 Here is another strategy
00:06:44.02 for catching fish.
00:06:45.12 This is another
00:06:46.06 group of cone snails.
00:06:47.01 These guys
00:06:48.03 when they are close
00:06:49.13 to a fish they open
00:06:50.10 their mouth,
00:06:50.24 and this species,
00:06:52.08 the Tulip Cone,
00:06:53.02 has frills at the end
00:06:54.03 of its mouth
00:06:55.11 and what they do
00:06:56.04 is they always engulf
00:06:57.14 the fish first,
00:06:58.15 and only when they have
00:06:59.15 englufed the fish
00:07:00.12 do they harpoon
00:07:02.04 their prey.
00:07:03.04 And so it's a different way
00:07:04.14 of catching a fish.
00:07:04.27 We call this
00:07:05.22 the "net strategy".
00:07:06.20 So how do you study
00:07:10.17 how these venoms act?
00:07:12.00 And one of the ways
00:07:14.04 to do it
00:07:15.08 is to purify
00:07:17.12 the different components
00:07:19.02 of the venom.
00:07:19.26 And you need an assay for that.
00:07:22.03 So at the beginning
00:07:23.25 of our work, we were
00:07:24.24 interested in the
00:07:26.11 components of the venom
00:07:27.18 that potentially
00:07:28.21 could kill people
00:07:30.08 because they cause paralysis.
00:07:31.24 And so our assay
00:07:33.04 was to use mice
00:07:34.18 and what we would do
00:07:36.14 is we would put mice
00:07:37.06 upside down on a
00:07:38.13 wire screen
00:07:39.18 and inject different
00:07:40.20 fractions of the venom
00:07:42.08 and some fractions
00:07:43.15 had no effect at all
00:07:45.03 in fact, most fractions,
00:07:46.17 but a few fractions
00:07:47.05 caused the mouse
00:07:48.21 to start to be paralyzed
00:07:50.02 and if it is paralyzed
00:07:51.27 it can't clench
00:07:53.06 its paws
00:07:53.25 and hang on
00:07:54.13 to the wire screen
00:07:55.16 and so it would fall.
00:07:56.27 So what we did was we just
00:07:59.01 characterized and purified
00:08:01.29 those components
00:08:02.08 that made the mouse fall
00:08:03.28 and that way we isolated
00:08:06.19 using this assay,
00:08:08.11 the first two components
00:08:09.06 of the venom
00:08:10.04 and these are their structures
00:08:12.08 And we were surprised to find
00:08:14.07 that the active
00:08:15.10 components of the venom
00:08:16.23 are like very small
00:08:18.07 proteins called peptides.
00:08:19.20 And so the first peptide
00:08:22.15 that we isolated
00:08:23.17 acts very much like
00:08:24.26 cobratoxin
00:08:25.20 or bungarotoxin
00:08:26.25 from snakes.
00:08:27.23 And the second
00:08:28.13 peptide we isolated acts
00:08:30.16 very much like
00:08:31.29 the deadly toxin
00:08:33.08 that you have
00:08:33.22 in pufferfish.
00:08:35.05 And so when you get
00:08:36.00 stung by one of these
00:08:37.15 snails, these Geographus cones,
00:08:39.27 it's equivalent
00:08:41.04 to being bitten by
00:08:42.06 a cobra
00:08:42.16 and eating a lethal dose
00:08:44.14 of pufferfish
00:08:45.07 at the same time.
00:08:46.09 And these are the chemicals
00:08:47.14 that really cause that.
00:08:48.29 They are small proteins.
00:08:50.09 with the sequences
00:08:51.15 that you can see here.
00:08:53.02 Then our whole research
00:08:57.01 outlook changed
00:08:58.05 because a young undergraduate,
00:09:00.04 an 18 year old kid,
00:09:01.06 came into the lab
00:09:02.11 and he said, you know, you guys
00:09:03.29 have been injecting the mice
00:09:05.25 directly in their body cavity.
00:09:08.23 I really think
00:09:09.28 that it would be better
00:09:11.06 if you injected mice
00:09:12.12 directly
00:09:13.06 into their central nervous system.
00:09:14.26 And I wasn't so persuaded
00:09:16.21 by this, but the great thing
00:09:18.12 about being at a University
00:09:19.15 is the students do
00:09:20.25 what they want.
00:09:21.13 They don't necessarily
00:09:22.23 follow the professor's advice.
00:09:26.02 And that really is
00:09:26.13 the source of a lot of
00:09:27.12 creativity
00:09:28.06 of the research in universities.
00:09:30.28 And so what this kid found
00:09:32.17 was that if he injected directly
00:09:35.04 into the brain
00:09:36.03 of a mouse,
00:09:36.26 that each component
00:09:38.25 of the venom
00:09:40.21 and each peak
00:09:41.24 here is one component
00:09:43.15 of the venom
00:09:44.02 caused a different
00:09:45.29 kind of behavior
00:09:48.04 in the mice.
00:09:49.07 So while there were some
00:09:50.16 components that
00:09:51.18 paralyzed mice
00:09:52.19 other made them jump
00:09:54.03 and twist as they are jumping.
00:09:55.10 Others made them uncoordinated.
00:09:57.29 And this major peak
00:09:59.02 that I am showing you here,
00:10:00.20 it put mice to sleep
00:10:02.25 and we were just amazed
00:10:03.17 becuase the mice
00:10:04.09 would go to sleep
00:10:05.09 and 12-24 hours later
00:10:06.07 they'd be perfectly fine,
00:10:08.23 but that was only true
00:10:10.03 if the mice were under three weeks of age,
00:10:12.05 If they were over three weeks of age
00:10:14.01 then instead of going to sleep
00:10:15.19 they would climb the sides of their cages
00:10:17.06 and run from corner to corner.
00:10:19.07 And then other peptides made
00:10:20.20 mice drag their back legs
00:10:23.16 or run around in circles
00:10:24.18 or swing their heads
00:10:25.18 back and forth
00:10:26.25 or kick on their
00:10:27.13 back and stretch
00:10:28.21 or scramble or scratch
00:10:30.26 and convulse.
00:10:32.16 And so the remarkable thing
00:10:34.02 was that all of this stuff
00:10:35.10 was found in one venom.
00:10:37.06 And so that tells us that
00:10:38.17 the venoms of these
00:10:39.20 snails were
00:10:40.16 extremely complex
00:10:42.03 with lots and lots
00:10:42.29 of bioactive things.
00:10:44.26 And so we have been trying to figure
00:10:45.21 this out ever since.
00:10:46.19 So why are there so
00:10:48.21 many peptides?
00:10:50.04 And it turns out
00:10:50.11 that some peptides
00:10:51.16 are used to capture prey,
00:10:52.26 some peptides
00:10:54.13 are used to defend themselves
00:10:56.18 agains predators
00:10:57.16 and some are to deter
00:10:59.04 competitors.
00:11:00.16 And so every species
00:11:02.07 of cone snail has a set
00:11:03.13 of biological interactions.
00:11:04.18 And each species is different.
00:11:07.17 So a different Conus species
00:11:11.27 would have different prey,
00:11:13.10 different predators
00:11:14.25 and different competitors.
00:11:16.15 In other words, each species
00:11:18.19 has its own
00:11:19.10 particular ecological niche
00:11:20.20 and so the venom
00:11:22.01 components are essentially
00:11:25.19 mutated
00:11:26.15 as species evolve
00:11:28.17 so that each is very fit
00:11:31.06 for its own particular
00:11:32.26 ecological niche.
00:11:33.26 So the study of cone snails
00:11:37.08 and specifically this one
00:11:39.06 led to the isolation
00:11:41.12 of one of these venom components
00:11:43.00 that turned out to have
00:11:46.00 a use that we never expected.
00:11:47.16 Today, that venom
00:11:49.05 component
00:11:50.00 is an approved drug
00:11:52.20 for very severe pain.
00:11:54.22 And so when your pain
00:11:55.19 is so severe
00:11:57.10 that even morphine doesn't help
00:11:59.00 then the component
00:12:00.26 of this cone snail venom
00:12:02.14 can help you in a lot of cases.
00:12:06.04 So this was
00:12:07.03 really unexpected
00:12:08.00 that by studying this very
00:12:11.11 seemingly esoteric
00:12:13.18 group of snails
00:12:14.22 we were able to
00:12:16.23 end up with
00:12:17.18 a drug for pain
00:12:18.27 that now is used
00:12:20.16 by people
00:12:22.11 in very severe pain.
00:12:23.16 Thank you very much.
00:12:24.19

This Talk

Speaker: Baldomero "Toto" Olivera

Audience:

Educators of H. School / Intro Undergrad
Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: October 2014

Talk Overview

Marine cone venomous snails are predators that use a purely chemical mechanism for catching their prey. There are over 700 types of venomous snails, each of which has a unique venom that can help the cone snail capture fish, worms, and even other venomous snails. In this talk, Dr. Baldomero “Toto” Olivera describes different types of venomous snails, and how his lab purified venom from one cone snail species and found that it was composed of a variety of small peptide toxins that induced specific neurological responses in the prey. One of these small peptides has since been approved to treat humans for severe pain.

Speaker Bio

Baldomero "Toto" Olivera

Toto Olivera

Baldomero “Toto” Olivera received a B.S. degree in Chemistry from the University of the Philippines, a PhD in Biophysical Chemistry from Caltech and did his postdoctoral work at Stanford University. His early research contributions included the discovery and biochemical characterization of E. coli DNA ligase. His laboratory initiated the identification and characterization of the biologically… Continue Reading