If they had told Clevers about their project before they started, he would have told them that it was extremely unlikely to work. The lab produces organoids with a cocktail of human proteins and growth factors, and there was no reason to think these would work on snake stem cells. And yet, they did. The only change the students made was to grow the organoids at a lower temperature than the usual 98 degrees Fahrenheit, because reptile bodies run cooler than mammalian ones. Clevers’s team can now produce lab-grown venom glands that generate the same chemical cocktail as their real counterparts. They’ve grown organoids from eight different species, all sourced as eggs from breeders or as euthanized individuals from zoos.
Read: How to kill a snake when you’re a snake
The resulting organoids look like white, millimeter-wide balloons. As they grow, they fill up with venom, which the team can harvest. Actual snake venom consists of dozens of proteins; many of these aren’t toxic on their own, but become so after being modified by enzymes in the gland. Organoid venom, the team discovered, is a close match to the real deal. It consists of the right proteins, which seem to have been modified in the right way. Other researchers have managed to preserve pieces of tissue from venom glands before, but these fragments have a limited shelf life. By contrast, the organoids are stable and can be grown in the billions.
There’s something a little sinister about a lab that can mass-produce snake venom, but these organoids have many beneficial uses. Snakebites, which kill between 81,000 and 138,000 people every year, have been described as “arguably the world’s biggest hidden health crisis.” In the time you have spent reading this article so far, 20 people have been bitten, 10 have been injected with venom, and two will either die or be permanently disabled. Still, research into venom has historically been underfunded, in part because it is so difficult to work with. Venom must be “milked” from living snakes, which is a dangerous and laborious process. There are also thousands of species of venomous snakes, many of which are rare and hard to collect.
Such work might become unnecessary if Clevers’s team can make organoids from enough species. Researchers could then have ready supplies of glands and venom. They could more easily study how venom is produced, how it varies among species, and how that variation influences the severity of a bite and the efficacy of an antivenom. Clevers and his colleagues are now trying to build a library of venom-gland organoids from about 50 target species. “You can grow them and send them around the world, and now the whole world can do work on an interesting snake,” he said.
Antivenom, the only proven treatment for snakebites, is made by collecting venom from live snakes, injecting it into horses, and harvesting the antibodies that the animals produce—a technique that hasn’t changed for centuries. Organoids offer a more modern approach: Scientists could use the mini-glands to produce specific toxins, then screen for molecules that neutralize those toxins. “Although such benefits for snakebite victims may be a number of years away, the venom-gland organoids provide us with a powerful new tool to progress snakebite research towards this goal,” says Nicholas Casewell of the Liverpool School of Tropical Medicine, who worked with Clevers on this project.