TOXINS IN AMPHIBIANS AND REPTILES
CHAPTER 1: GENERAL INTRODUCTION AND OVERVIEW OF POSIONOUS / VENOMOUS TAXA
• The study of animal toxins is beneficial for a number of biological and applied science fields…
→ Animal physiology, biochemistry, cellular biology, ecology, ethology, evolutionary biology, immunology,
molecular genetics, pharmacology, medicine, taxonomy, organic chemistry…
→ … and knowledge of these fields = possible to study animal toxins
• Example: 3D structure of Erabutoxin b
→ A neurotoxin produced by the sea snake Laticauda semifasciata (the black-banded
sea krait)
• Most toxins are proteins → genetic material codes for a toxin
1.1. SOME TERMINOLOGY TO START WITH
1.1.1. WHAT IS A TOXIN?
• Theophrastus of Hohenheim (Paracelsus) (1493-1541)
→ “All things are poison and nothing is without poison. Only the dose makes a thing not to be a poison.”
▪ Eg. water can be toxic
▪ Biological context: low dose and still a hard effect (eg. lethal, but a slight pain or an itch as well!)
• Wikipedia:
→ “A natural occurring organic poison produced by metabolic activities of living cells or organisms.”
→ So, Wikipedia shifts the problem → what is a poison? → Wikipedia:
▪ “Any chemical substance that is harmful or lethal to living organisms.”
→ The Wikipedia definitions emphasize the potential negative effect of a substance
→ These definitions differ from what is currently used in scientific literature
→ Eg. because what is the difference between a venom and a poison?
• Ecological definition:
→ “A molecule used by one organism to cause a biochemical effect in another in function of predation,
defense or competition.”
▪ Eg. competition: the cane toad in Australia: their tadpoles release toxins that inhibit growth of
additional toads of the same species! = intraspecific competition to ensure they are not too
abundant
▪ Eg. competition: platypus: venom for intraspecific competition
→ The prof has helped invent this definition!
→ This definition emphasizes the functional value of a molecule (so, why the molecule is used)
→ It doesn’t say anything about how harmful it is or what the negative effects are
• Revised definition:
→ A classification based on type of toxin
→ Biological toxin (biotoxin): a substance produced by a living organism that is capable of causing dose-
dependent pathophysiological injury to itself (suicide toxin) or another living organism
→ Environmental toxin: a naturally occurring substance in the environment that is not produced by an
organism but it capable of causing dose-dependent pathophysiological injury to a living organism
▪ Eg. mercury, arsenic, lead
→ Anthropogenic toxin (a toxicant): a substance produced by humans that does not otherwise occur in
the environment, which is capable of causing dose-dependent pathophysiological injury to a living
organism
▪ Eg. DDT, dioxin, PCBs
• On exam: you don’t have to give a the definition because you could write ‘a whole page about it’
• Just know that it is not that simple !
1
,1.1.2. WHAT IS A BIOACTIVE MOLECULE?
• A term commonly used in the field of pharmacology
• “A molecule with a biological effect on living matter (cells, tissues or organisms)”
→ Eg. lytic effect, increase of blood pressure…
→ The effect is not necessary toxic related
• Note: this definition does not specify whether this effect is beneficial or adverse
→ Toxins (-) are bioactive molecules, but drugs are too (+)
• Bioactivity mostly used in terms of a desired effect of a potential drug candidate → mostly used by scientists
• Scientist are interested in toxins:
→ Eg. a toxin that lowers the blood pressure = bad for certain animal, but some people need it
1.1.3. TOXICOLOGY vs. TOXINOLOGY
Toxicology:
• The scientific discipline dealing with the adverse effects of chemicals on living organisms, communities,
ecosystems. It is the study of symptoms, mechanisms, treatments and detection of poisoning
• Eg. release of mercury in a lake
Toxinology:
• “The scientific discipline dealing with microbial, plant and animal venoms, poisons and toxins”
• “The science of toxic substances produced by or accumulated in living organisms, their properties, and their
biological significance for the organisms involved”
• So: the study of biological toxins and all of their aspects (pathophysiol., treatment, ecology, evolution)
• Eg. snake envenomation (vergiftiging)
Snake bites
• Are considered a tropical disease (World Health Organization)
• Toxino: examine the snake toxin itself
• Toxico: it has an effect on the whole human population
1.1.4. VENOM vs. POISON
Venom
• A toxin or mixture thereof used by an animal and injected into the circulatory system (eg. blood stream or
lymphatic system) of another animal, often by means of a specialized venom delivery structure (eg. fangs,
beaks, spines, stinger…) + often causing a wound
• They may have a predatory and/or defense function
• Derived words: venomous, envenomation, venom glands
• Venom and venomous only apply to animals
• Eg. some protist single cells use a harpoon to paralyze other cells (even though they have no CNS!)
Poison
• A toxin or mixture thereof that is passively administered through epithelia (eg. skin, gills, lungs, intestines) by
absorption, ingestion or inhaling
• Poisons in biology mostly have a defensive function
• Derived words: poisonous, poisoning, poison glands
• Almost all amphibians are poisonous (producing toxins in their skin) → must be ingested
• Plants are called poisonous, not venomous, even if they use spines to inject the toxins!
→ Eg. you have to touch them, so it is passive ↔ but what with carnivore plants?
2
, • So phylogenetically, poison is wider than venom because plants are incorporated
But: sea urchin = venomous, although you have to step on it = passive → so: venom/poison is hard to determine
→ there is no clear definition, it is more subjective
Venom is often more effective than poison: it has a faster response
Toxunogen
• A toxic substance (comprised of one or more toxins) causing dose-dependent physiological injury tat is
actively transferred via a delivery mechanism from one organism to the external surface of another organism
without mechanical injury
• Eg. secretions that are projected or sprayed to fend off an attacking predator
• They “launch” their toxin
EXAMPLES: VENOMOUS OR POISONOUS
1. Irukandji jellyfish: venomous → they sting other animals and
make a small injury
→ Nematocyst ; via mechanical triggering
2. Sea apple (echinoderm): poisonous → they are advertising
their toxicity by bright colors: “don’t eat me”
3. Flower urchin: venomous → special sea urchin, it has claws: it
will grab you and inject its toxin
4. Blue-ringed octopus:
→ venomous → lethal bite via a beak (< chitine, so a hard
bite) = neurotoxin
→ poisonous → it tissue is toxic via symbiotic bacteria that live
in there
5. Bulldog ant: venomous → stinger like a wasp (so not a beak) ; sit
on flowers and grab bees
→ Primitive! Most ants lost their toxicity
6. Pyrenean brook salamander: poisonous
7. Spanish rib salamander: poisonous (same glands as previous one
in skin) + venomous (!) → uses its ribs to attack the predator via a mechanical injury
→ When under attack, they’ll perforate their own skin (will regrow) → toxin secreted
through the spines
8. Fire salamander: toxunogen ? → spray toxins in face of predator ; poisonous (bright
colors)
1.2. POISON/VENOM IN THE ANIMAL KINGDOM
• Poison and venom systems are widespread in Animalia/Metazoans
and occur in modern representatives of the major animal lineages
• 3 major names: Metazoa, Bilateria, Deuterostomia
• Metazoa = all animals having the body composed of cells
differentiated into tissues and organs and usually a digestive cavity
lined with specialized cells
• Red = venom ; purple = poison
3
, 1.2.1. PORIFERA
• The sponges = primitive lineage → although already toxins present → not per se lethal
→ Animals limited in their tissue differentiation and
development
• Secreting molecules that can be irritating + can cause an injury
→ Needle-like strands of spicules containing irritating toxins
• So poisonous because passive
• But venomous as well because sometimes injury
1.2.2. CNIDARIANS
• Anthozoa: corals and sea anemones
• Medusozoa: jellyfish
• All of them venomous
• They all use the same toxin delivery system at
subcellular level (although a very diverse body plan)
• Fish can be paralyzed within seconds (sometimes
humans as well)
• Corals = less dangerous because sessile
• Nematocyste (cnidocyte)
→ Specialized cells that ‘fire’ venom
→ Organelle (nematocyst) into prey when triggered
→ Sticky
1.2.3. PLATYHELMINTES
• Flatworms
• Planicera multitentaculata (picture): the neurotoxin Tetradotoxin (TTX) has been
detected in various tissues, including eggs: defense function?
• ‘Planocerid sp.1’ uses TTX to immobilize gastropod prey by enveloping the victim and
secreting TTX (hunting)
→ A poison for predation! So NOT always as defense!!! Unique!
1.2.4. NEMERTEA
• Ribbon worms (snoerwormen)
• Carnivorous nemerteans use a proboscis to entangle or stab prey
→ In some species, like Paranemertes peregrina, this structure secretes paralytic toxins, incl. TTX
→ Small claws sometimes on proboscis
→ Paralyze prey
INTERMEZZO: toxins evolved multiple times in evolution
➔ Almost all marine organisms use same toxin: TTX → via a symbiosis with bacteria that produce the TTX
➔ Sometimes TTX in amphibians as well
1.2.5. MOLLUSCA
Gastropoda
• Different delivery modi known
• Most cone snails (genus Conus) use a venomous harpoon to capture and paralyze prey
→ Often used as painkilling drugs in pharmacology (paralyzing nervous system)
• Some Conus species however, engulf their fish prey and release a ‘nirvana cabal’ (a mixture of toxins)
→ Several are highly potent insulin analogs → rapidly depleting sugar levels in the prey’s blood
4
CHAPTER 1: GENERAL INTRODUCTION AND OVERVIEW OF POSIONOUS / VENOMOUS TAXA
• The study of animal toxins is beneficial for a number of biological and applied science fields…
→ Animal physiology, biochemistry, cellular biology, ecology, ethology, evolutionary biology, immunology,
molecular genetics, pharmacology, medicine, taxonomy, organic chemistry…
→ … and knowledge of these fields = possible to study animal toxins
• Example: 3D structure of Erabutoxin b
→ A neurotoxin produced by the sea snake Laticauda semifasciata (the black-banded
sea krait)
• Most toxins are proteins → genetic material codes for a toxin
1.1. SOME TERMINOLOGY TO START WITH
1.1.1. WHAT IS A TOXIN?
• Theophrastus of Hohenheim (Paracelsus) (1493-1541)
→ “All things are poison and nothing is without poison. Only the dose makes a thing not to be a poison.”
▪ Eg. water can be toxic
▪ Biological context: low dose and still a hard effect (eg. lethal, but a slight pain or an itch as well!)
• Wikipedia:
→ “A natural occurring organic poison produced by metabolic activities of living cells or organisms.”
→ So, Wikipedia shifts the problem → what is a poison? → Wikipedia:
▪ “Any chemical substance that is harmful or lethal to living organisms.”
→ The Wikipedia definitions emphasize the potential negative effect of a substance
→ These definitions differ from what is currently used in scientific literature
→ Eg. because what is the difference between a venom and a poison?
• Ecological definition:
→ “A molecule used by one organism to cause a biochemical effect in another in function of predation,
defense or competition.”
▪ Eg. competition: the cane toad in Australia: their tadpoles release toxins that inhibit growth of
additional toads of the same species! = intraspecific competition to ensure they are not too
abundant
▪ Eg. competition: platypus: venom for intraspecific competition
→ The prof has helped invent this definition!
→ This definition emphasizes the functional value of a molecule (so, why the molecule is used)
→ It doesn’t say anything about how harmful it is or what the negative effects are
• Revised definition:
→ A classification based on type of toxin
→ Biological toxin (biotoxin): a substance produced by a living organism that is capable of causing dose-
dependent pathophysiological injury to itself (suicide toxin) or another living organism
→ Environmental toxin: a naturally occurring substance in the environment that is not produced by an
organism but it capable of causing dose-dependent pathophysiological injury to a living organism
▪ Eg. mercury, arsenic, lead
→ Anthropogenic toxin (a toxicant): a substance produced by humans that does not otherwise occur in
the environment, which is capable of causing dose-dependent pathophysiological injury to a living
organism
▪ Eg. DDT, dioxin, PCBs
• On exam: you don’t have to give a the definition because you could write ‘a whole page about it’
• Just know that it is not that simple !
1
,1.1.2. WHAT IS A BIOACTIVE MOLECULE?
• A term commonly used in the field of pharmacology
• “A molecule with a biological effect on living matter (cells, tissues or organisms)”
→ Eg. lytic effect, increase of blood pressure…
→ The effect is not necessary toxic related
• Note: this definition does not specify whether this effect is beneficial or adverse
→ Toxins (-) are bioactive molecules, but drugs are too (+)
• Bioactivity mostly used in terms of a desired effect of a potential drug candidate → mostly used by scientists
• Scientist are interested in toxins:
→ Eg. a toxin that lowers the blood pressure = bad for certain animal, but some people need it
1.1.3. TOXICOLOGY vs. TOXINOLOGY
Toxicology:
• The scientific discipline dealing with the adverse effects of chemicals on living organisms, communities,
ecosystems. It is the study of symptoms, mechanisms, treatments and detection of poisoning
• Eg. release of mercury in a lake
Toxinology:
• “The scientific discipline dealing with microbial, plant and animal venoms, poisons and toxins”
• “The science of toxic substances produced by or accumulated in living organisms, their properties, and their
biological significance for the organisms involved”
• So: the study of biological toxins and all of their aspects (pathophysiol., treatment, ecology, evolution)
• Eg. snake envenomation (vergiftiging)
Snake bites
• Are considered a tropical disease (World Health Organization)
• Toxino: examine the snake toxin itself
• Toxico: it has an effect on the whole human population
1.1.4. VENOM vs. POISON
Venom
• A toxin or mixture thereof used by an animal and injected into the circulatory system (eg. blood stream or
lymphatic system) of another animal, often by means of a specialized venom delivery structure (eg. fangs,
beaks, spines, stinger…) + often causing a wound
• They may have a predatory and/or defense function
• Derived words: venomous, envenomation, venom glands
• Venom and venomous only apply to animals
• Eg. some protist single cells use a harpoon to paralyze other cells (even though they have no CNS!)
Poison
• A toxin or mixture thereof that is passively administered through epithelia (eg. skin, gills, lungs, intestines) by
absorption, ingestion or inhaling
• Poisons in biology mostly have a defensive function
• Derived words: poisonous, poisoning, poison glands
• Almost all amphibians are poisonous (producing toxins in their skin) → must be ingested
• Plants are called poisonous, not venomous, even if they use spines to inject the toxins!
→ Eg. you have to touch them, so it is passive ↔ but what with carnivore plants?
2
, • So phylogenetically, poison is wider than venom because plants are incorporated
But: sea urchin = venomous, although you have to step on it = passive → so: venom/poison is hard to determine
→ there is no clear definition, it is more subjective
Venom is often more effective than poison: it has a faster response
Toxunogen
• A toxic substance (comprised of one or more toxins) causing dose-dependent physiological injury tat is
actively transferred via a delivery mechanism from one organism to the external surface of another organism
without mechanical injury
• Eg. secretions that are projected or sprayed to fend off an attacking predator
• They “launch” their toxin
EXAMPLES: VENOMOUS OR POISONOUS
1. Irukandji jellyfish: venomous → they sting other animals and
make a small injury
→ Nematocyst ; via mechanical triggering
2. Sea apple (echinoderm): poisonous → they are advertising
their toxicity by bright colors: “don’t eat me”
3. Flower urchin: venomous → special sea urchin, it has claws: it
will grab you and inject its toxin
4. Blue-ringed octopus:
→ venomous → lethal bite via a beak (< chitine, so a hard
bite) = neurotoxin
→ poisonous → it tissue is toxic via symbiotic bacteria that live
in there
5. Bulldog ant: venomous → stinger like a wasp (so not a beak) ; sit
on flowers and grab bees
→ Primitive! Most ants lost their toxicity
6. Pyrenean brook salamander: poisonous
7. Spanish rib salamander: poisonous (same glands as previous one
in skin) + venomous (!) → uses its ribs to attack the predator via a mechanical injury
→ When under attack, they’ll perforate their own skin (will regrow) → toxin secreted
through the spines
8. Fire salamander: toxunogen ? → spray toxins in face of predator ; poisonous (bright
colors)
1.2. POISON/VENOM IN THE ANIMAL KINGDOM
• Poison and venom systems are widespread in Animalia/Metazoans
and occur in modern representatives of the major animal lineages
• 3 major names: Metazoa, Bilateria, Deuterostomia
• Metazoa = all animals having the body composed of cells
differentiated into tissues and organs and usually a digestive cavity
lined with specialized cells
• Red = venom ; purple = poison
3
, 1.2.1. PORIFERA
• The sponges = primitive lineage → although already toxins present → not per se lethal
→ Animals limited in their tissue differentiation and
development
• Secreting molecules that can be irritating + can cause an injury
→ Needle-like strands of spicules containing irritating toxins
• So poisonous because passive
• But venomous as well because sometimes injury
1.2.2. CNIDARIANS
• Anthozoa: corals and sea anemones
• Medusozoa: jellyfish
• All of them venomous
• They all use the same toxin delivery system at
subcellular level (although a very diverse body plan)
• Fish can be paralyzed within seconds (sometimes
humans as well)
• Corals = less dangerous because sessile
• Nematocyste (cnidocyte)
→ Specialized cells that ‘fire’ venom
→ Organelle (nematocyst) into prey when triggered
→ Sticky
1.2.3. PLATYHELMINTES
• Flatworms
• Planicera multitentaculata (picture): the neurotoxin Tetradotoxin (TTX) has been
detected in various tissues, including eggs: defense function?
• ‘Planocerid sp.1’ uses TTX to immobilize gastropod prey by enveloping the victim and
secreting TTX (hunting)
→ A poison for predation! So NOT always as defense!!! Unique!
1.2.4. NEMERTEA
• Ribbon worms (snoerwormen)
• Carnivorous nemerteans use a proboscis to entangle or stab prey
→ In some species, like Paranemertes peregrina, this structure secretes paralytic toxins, incl. TTX
→ Small claws sometimes on proboscis
→ Paralyze prey
INTERMEZZO: toxins evolved multiple times in evolution
➔ Almost all marine organisms use same toxin: TTX → via a symbiosis with bacteria that produce the TTX
➔ Sometimes TTX in amphibians as well
1.2.5. MOLLUSCA
Gastropoda
• Different delivery modi known
• Most cone snails (genus Conus) use a venomous harpoon to capture and paralyze prey
→ Often used as painkilling drugs in pharmacology (paralyzing nervous system)
• Some Conus species however, engulf their fish prey and release a ‘nirvana cabal’ (a mixture of toxins)
→ Several are highly potent insulin analogs → rapidly depleting sugar levels in the prey’s blood
4
