A Lesson from Snails
Darwin R. Del Rosario
The Philippine archipelago hosts a large biodiversity of rich marine flora and fauna. Among the latter are the venomous cone snails (Fig. 1) found in our abundant coral reefs. These cone snails, depending on their species, may either hunt for fish, worms or other snails by injecting venom to their prey via their proboscis and ingesting them through their siphon which greatly expands.
Dr. Baldomero Olivera is a Filipino scientist who has conceived research on these snails, particularly their venom. He, along with other individuals, was able to isolate a certain component of the venom which was discovered to act as a painkiller in humans. This component, a peptide, is now a commercial medicine used to treat pain known as Prialt (or primary alternative to morphine).
However, when a peptide is injected into the central nervous system of animals, they produce a different effect since they do not pass through the blood stream and consequently, do not target the organism's specific organs. A specific peptide in the venom of these cone snails, known as the “shaker-peptide”, induces shaking to the fish when injected to the fish’s nervous system.
Although this case is true for fishes, the shaker-peptide had a far different effect when introduced to the central nervous system of mice. It was discovered to be beneficial since it acted as an analgesic or a painkiller.
The shaker-peptide of the venom is also known as Prialt.
To explain this, we look at how Prialt affects the nerves at their neuro-muscular junction. When the brain sends a signal to the neuro-muscular junction, the signal is passed to the muscle at the synapse through a neurotransmitter known as acetylcholine. Acetylcholine is released by the vessels in the nerve. However, these vessels only fuse and release acetylcholine upon its stimulation by calcium ions. These calcium ions pass through calcium channels which open when the signal reaches the nerve ending. The process is summarized in the following diagram.
What Prialt does to fishes is that it blocks the calcium channels (Fig. 3), thus inhibiting the transmission of signals from nerve to muscle, thereby paralyzing the fish and causing its seizures (shaking).
Note that these calcium channels are found specifically in in the synapses at the neuro-muscular junction of fishes (Fig. 4), thus are affected by the blocking of Prialt. This is what causes the fish to be paralyzed.
However, for mammals such as mice and humans, the calcium channels at the neuro-muscular junction (Fig. 5) are of a different type, thus are not affected by Prialt.
In mammals, what is affected by Prialt are the synapses between pain fibers and the nerves of the spinal cord (Fig. 6) because the calcium channels found in the ends of these pain fibers are the same calcium channels found in the neuro-muscular junction of fishes. This is possible because the nervous systems of animals have the same basic components. Meaning, molecules of our nerves are very conserved, thus the calcium channels found in the neuro-muscular junction of fishes are similar to those of the calcium-channels found between the pain fibers and the spinal cord of humans.
Prialt, therefore, blocks the receptors from receiving pain signals to the central nervous system, thus acting as an analgesic to humans. This important breakthrough in Dr. Olivera’s research has caused the medicine to be commercialized and spark interest in the use of peptides as potential medicine. Prialt, which targets the synapses of nerves are therefore related to diseases such as schizophrenia and epilepsy because both are associated with dysfunction at their receptors and can possibly be a cure.
From venom to medicine- the scientific discovery of Dr. Olivera and his team basically suggests that more potential medicine can be taken from the peptides of a lethal weapon- venom. Aside from his research on these cone snails, Dr. Olivera has also taught in schools regarding Philippine biodiversity and marine biology.
Fusetani, N. et al. 2009. Marine Toxins as Research Tools. Berlin: Springer-Verlag Berlin Heidelberg.
Taylor, A.-L. 2011, December 31. How a venomous cone snail catches and kills fish. BBC Feature News.
Olvera, B. 2009. Exploring Biodiversity: The Search for New Medicines, Lecture 1 – From Venoms to Drugs. HHMI Holiday Lectures. Lecture conducted from Howard Hughes Medical Institute, Chevy Chase. http://media.hhmi.org/hl/09Lect1.html. March 1, 2014.