Snake in a test tube
The venom gland of snakes was first grown in the laboratory
To do this, scientists used stem cells of the South African shield cobra
Biologists from the Netherlands have turned the stem cells of snakes into an artificial analogue of their glands, which produce venom. The creation of such glands will significantly accelerate the emergence of new drugs and antidotes, scientists write in the scientific journal Cell (Post et al., Snake Venom Gland Organoids).
"Every year more than one hundred thousand people die from snake bites, most of them in developing countries. At the same time, the production technology of antidotes has hardly changed since the XIX century. It is absolutely clear that there is a demand for such drugs, which is currently not satisfied with anything," said Hans Klevers, one of the authors of the work, a molecular biologist from Utrecht University (the Netherlands).
Poisons and toxins of many fungi, snakes, fish and microbes are now actively used as components of various medicines, laboratory reagents and for a variety of other purposes. In particular, a few years ago, French biologists used the venom of the black mamba to create mambalgin, a very effective painkiller that does not cause addiction.
Their Russian colleagues, in turn, found another powerful analgesic in the tentacles of sea polyps – anemones, and also found a very fast analogue of insulin in the venom of sea snails-cones. All these substances, scientists hope, will help to create more effective or unique medicines in the very near future.
Clevers and his colleagues found out how to dramatically speed up the process of studying, searching and even creating such molecules by experimenting with stem cells of the South African shield cobra (Aspidelaps lubricus), a venomous snake whose bite is dangerous to humans, but does not always cause death. For these experiments, the scientists used several fertilized cobra eggs.
"We were afraid that we would not be able to isolate stem cells from the future poisonous glands of embryos, since we did not know what they looked like. It turned out that this was not a problem – the cells immediately began to divide and form structures. Moreover, the analogues of the poisonous glands grew so fast that after a week they could be divided into parts and begin to grow again," continues Klevers.
Biologists have turned these cultures into full-fledged analogues of snake venom glands by treating stem cells with a special "cocktail" of signaling molecules. They forced the stem cells to turn into the necessary components of the poisonous glands. To start this process, scientists lowered the temperature of the nutrient medium from 37°C to 32°C, which is usual for mammals.
Subsequent experiments showed that miniature copies of the venom glands of the shield cobra grew very quickly and produced large amounts of poison. Biologists have tested his work on mouse muscle cell cultures and rat neurons. These successes forced scientists to grow similar organoids from the germ bodies of a number of other snakes, including Cape cobras (Naja nivea), one of the most venomous and dangerous reptiles in Africa, as well as Texas rattlesnakes. (Crotalus atrox) and other dangerous snakes of the New World.
Already, as the researchers note, such an approach works much faster than growing and "milking" snakes on farms. In addition, it is cheaper than the production of poison or antidotes by transplanting snake genes into the genome of microbes and yeast. Now Dutch biologists are creating a kind of "library" of 50 types of similar artificial venom glands of different types of snakes. Working with her will help doctors save the lives of many thousands of people bitten by these reptiles, Klevers and his colleagues conclude.
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