The sugar trap

Research: Snails use insulin to hunt fish

When we think of predator and prey, I guess most of us imagine a lion chasing a zebra in the African savannah. This means that we probably see many nature films, but maybe not enough variety. The natural world is full of a rich and huge variety of predators, who with the kind help of mother-evolution have developed different techniques for capturing prey. Many of them - in honor of the King of the Beasts - are much more sophisticated and fascinating than running faster than the prey and sinking your teeth into it. There are predators that lay traps for their prey, such as the haremnel caterpillar that traps ants in a pit with crumbling sides, or the slender spider webs that catch insects in flight. Predators like the albon fish camouflage themselves perfectly and emerge from their lair quickly only when the innocent prey passes near them. Others have developed a certain organ to perfection, like the tongue of lizards or frogs which is pulled out with incredible speed to catch an insect in flight. Some predators cooperate in groups, to allow them to attack animals that are much larger and stronger than them, such as hyenas, wolves or even piranhas. Other predators have developed unique strategies, such as the sniper fish, which spits a precise jet of water at insects sitting on leaves outside the water, drops them into the water and swallows them. Some eels stun their prey with an electric shock, allowing them to devour it.

My favorite predators - personally - are the ones that have developed special chemical methods to capture their prey: for example, spiders or wasps that inject the prey with a paralyzing substance, and then do with it as they wish. Other venomous predators, such as snakes or scorpions, do not bother to immobilize their prey, but simply kill it with a dose of poison, and then eat it. Other chemical predators do not inject the poison into their prey, but simply excrete it into the water, so for example various jellyfish kill or paralyze fry or other unfortunate creatures that have fallen into their environment. One of the most fascinating creatures in the field of venom use is an innocent-looking sea snail that makes extensive use of biochemical tools, and new research reveals its great sophistication.

Pain reliever snail

The cone snails (Conidae) are a family that includes about 500 different species of snails with a cone-shaped shell. Some of the species are very small, others reach a size of 10-15 cm. About a hundred of the species in the family are fish predators. Despite their slowness, they are able to pull out a huge tongue-like organ, catch and wrap small fry with it and put them in their mouths. Some species of snails are successful in this operation, because beforehand they secrete a paralyzing poison into the water, and when they come into contact with the victim, they inject him with a particularly deadly poison.

One of the snails from this family, Conus geographus, has such a deadly venom that a few millionths of a gram of it is enough to kill an adult person, or paralyze him. It is estimated that tens of people have paid with their lives for careless contact with this snail and its related species. These deadly snails attracted the attention of a young Filipino scientist, Baldomero Olivera, who in the 60s did a doctorate in biophysics at the California Institute of Technology. He studied for many years the activity of the various toxins that make up snail venom - most of them are small proteins that paralyze certain activities of the nervous system.

Olivera's research was also the basis for the development of an important drug for chronic pain relief. A large part of the toxins damage the activity of ion channels. The channels are a kind of holes in the nerve cells, which can open and close very quickly, and allow the passage of only certain substances, such as potassium, chlorine, sodium or calcium. These substances are ions, i.e. atoms with an electrical charge, and a rapid change in their quantity results in a change in the electrical voltage in the nerve cell, which allows it to transmit signals to other cells, or alternatively - to block the passage of signals. One of the proteins discovered by Olivera blocks the activity of such a calcium channel, causing paralysis in fish. However, he realized that in humans, blocking this particular channel may prevent the release of substances that cause the sensation of pain in the brain. Indeed - a version of the toxin produced artificially in a laboratory forms the basis of the drug Prialt, which is used to treat severe chronic pain, for example in cancer patients. Since the drug is nevertheless a very deadly poison, it is only given by direct injection into the spinal fluid, with extreme care for the exact dosage (patients who received too high a dose in clinical trials suffered from severe hallucinations and impaired orientation).

Insulin paralyzes

Olivera, now a professor at the University of Utah, has been engaged in the study of cone snail toxins for several decades. In the current study, he tried to check with Dr. Helena Safavi-Hemami, who is doing a post-doctoral training with him, exactly how the long tongue of snails works. To do this, they examined the gene sequence of all the proteins in the snail's venom gland. A quick examination of the sequences turned up two sections that apparently weren't supposed to be there. These genes - the researchers realized - do not encode one of the poison proteins, but a much more familiar protein - insulin, which is used to regulate the sugar level in many creatures, including humans of course. A closer examination revealed that the insulin produced by the snails is not the same as the one they use to break down sugar. In contrast, it is biochemically identical to the insulin that exists in small fish, which the snails eat. The researchers hypothesized that the snail secretes insulin into the water along with paralyzing substances, which causes a rapid drop in the fish's sugar level, and impairs their reaction speed and orientation in the environment, which of course makes it difficult for them to escape from the predator.

Daze

To test this hypothesis, the researchers did some experiments. First, they looked for the insulin gene in other cone snails, and found another species, Conus tulipa, whose venom also contains insulin. In contrast, they did not find this gene in five species of fish-eating snails that do not secrete a paralyzing venom, but instead inject a deadly venom into the fish using a bell-like organ. Also, they did not find an insulin gene in some snail species that feed on molluscs and worms, and are not fish predators. In the next step, the researchers were able to produce a synthetic copy of the insulin from the snails in the laboratory. They injected the substance into zebra fish, and found out that it indeed causes a sharp drop in the level of sugar in their blood. Furthermore, the low sugar level brought about a behavioral change in the fish: the frequency of their movements decreased greatly, and the proportion of their swimming time (compared to the time spent in place), decreased considerably. The researchers hypothesize that the release of insulin into the water puts the fish into a kind of hypoglycemic shock, what we call a "sugar drop". In humans, a sharp drop in blood sugar can cause dizziness, blurred senses and even fainting, it turns out that the fish react in a similar way, and the researchers believe that insulin is a key component in the paralysis that grips the fish, allowing the snails to devour them.

Food for thought

The study, published in the Journal of the American Academy of Sciences (PNAS), is the first to demonstrate the use of insulin as a paralyzing agent for hunting purposes. It is very possible that there are more such examples, of which we are not aware at the moment. This finding also illustrates once again the wonders of evolution: a certain animal manages to produce an exact copy of a material present in another animal, and use it for a completely different purpose. Also, the research may shed new light on the functions of insulin, and may help scientists develop more effective, cheaper and simpler insulin substitutes, which will certainly be useful in the fight against the severe diabetes epidemic. Furthermore, as in the case of the perialet used for pain relief, any new research on the substances secreted by snails and other animals, may pave our way to the discovery of new substances that humans can benefit from.
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The research paper in the journal PNAS