Can a poisonous sea snail replace morphine?

Bea Ramiro from Department of Biomedical Sciences at Copenhagen University began to study the sea snail species Conus rolani more or less by chance. Together with two fishermen she was collecting material in the waters off the Philippine island of Cebu in 2018.

At the time, researchers knew that poison from the sea snail species Conus magus could be used as a painkiller. It can replace morphine and opioids, and some patients experience fewer side effects. Therefore, Bea Ramiro hoped she could find a new sea snail species whose poison had a similar or possibly even better effect.

In order to study sea snails, Bea Ramiro had to collect a lot of snails of the same species. And once the fishermen had reeled in the net and the snails had been divided into groups according to species, she only had enough snails of the species Conus rolani to do a proper study.

Today, Bea Ramiro is glad that this large, white and brown snail six to seven centimetres long was the only species left.

Because a new study from the University of Copenhagen to which she has contributed shows that poison from Conus rolani can function as a painkiller. The researchers have learned that a particular substance from the poison can block out pain in mice for an even longer time than morphine.

“We have discovered a so-called toxin that blocks out pain in a completely different way than well-known drugs like morphine, and hopefully this will enable us to avoid some of the most damaging effects of morphine on humans,” explains Associate Professor Helena Safavi, who has headed the study.

Today, medicine based on the sea snail Conus magus is already available in the market for treatment of e.g. back injuries and cancer. But it is both expensive and difficult to work with because it has to be injected into the central nervous system via e.g. a spinal implant.

So even though we already have a drug based on a sea snail which for some people involves fewer side effects than morphine and opioids, it is not ideal due to the price and the circumstances.

Therefore, the researchers behind the new study hope the discovery of the effect of poison from Conus rolani can help them develop a more efficient painkiller.

“We need a better alternative for people who are in great pain – an alternative that is less addictive than e.g. morphine and other opioids. In Denmark, opioids do not represent a huge problem, but in other parts of the world it is quite extensive,” says Helena Safavi from the Department of Biomedical Sciences at the University of Copenhagen.

A clever hunter

Conus rolani lives at a depth of 210 metres in the waters off Cebu in the Philippines. The species is merely one of more than 800 sea snail species, most of which use poison when they hunt for food. But Conus rolani is one of the cleverer hunters, Helena Safavi explains.

Because once the snail has harpooned its victim with poison, it waits, patiently. Not until up to three hours later, when the poison has begun to work and the victim is apathetic, does the snail catch it with its toothless mouth.

This may seem like an ineffective hunting strategy compared to other sea snails which cling to their victim immediately and whose poison works much faster.

“But we believe it does this to protect itself. It waits until the fish is so weak that it cannot struggle, whereas other sea snails with more fast-working poison risk getting hurt by clinging to their victim,” says Helena Safavi.

A similar hunting strategy is found among e.g. rattlesnakes and adders. But this is the first time researchers have seen a sea snail use it.

X-ray of sea snail poison

Helena Safavi has studied Conus rolani for more than three years now.

“Far too long,” she says laughing and explains that it has not been easy.

Once the researchers had collected the sea snails in the Philippines and observed their unique hunting strategy in an aquarium, they obtained the poison and separated the various components to learn which had interesting effects on mice.

The researchers characterised and produced synthetic ‘twins’ for the more than 100 toxins found in the sea snail’s poison. Subsequently, they X-rayed the one toxin that showed potential.

“We could see that the structure of the toxin from the sea snail’s poison resembled a somatostatin, which is a hormone found in the human body regulating the sensation of pain. This suggested that the toxin might have a similar regulating effect,” says Helena Safavi.

And testing the toxin on mice revealed to the researchers that it was just as efficient a painkiller as morphine, though with a more long-lasting effect.

“I was surprised that the toxin was so effective and that it lasted longer than morphine. This reveals its great future potential,” says Helena Safavi.

Nature offers us a shortcut

Not only sea snails inspire researchers to develop new drugs, says Helena Safavi.

“There is a pretty common drug called Capoten in the market used as a treatment for high blood pressure, and it is based on snake poison,” she explains.

“We can learn a lot from nature. And it makes good sense, because nature has had millions of years to refine e.g. sedative poisons, whereas we have only been at it for a couple of hundred years. So nature offers us a shortcut.”

According to Helena Safavi, this also applies to technology. For example, researchers are studying the fingers of the gecko, which enable the small lizard to climb up walls and ceilings. The researchers thereby hope to be able to develop a strong material that easily attaches to things and can be removed again. In addition, polar bears serve as inspiration for researchers eager to develop better insulation for our buildings.

“There is so much potential in nature, and if are able to decode it, we can make the world a better place,” says Helena Safavi.

Read the entire study "Samotostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads" in Science Advances.