Thank you to Trade Coffee for supporting this episode of SciShow.

You can go to drinktrade.com/scishowoffer to get a free bag of coffee with any subscription purchase. Let’s imagine you’ve been bitten by a snake.

The only thing between you and imminent death or serious injury might be…a horse. I mean a specific one. One that’s been exposed to the exact venom in question and has made antibodies against it, so they can be collected and given to you to combat the venom making its way through your system.

And if you’re thinking that horse-based medicine sounds 19th century at best, well, a lot of people agree with you and are working on ways to remove livestock from the equation. And that’s only part of the problem, because you need a different antivenom… and a different batch of horses or sheep… for pretty much every venom out there. Luckily, researchers are getting closer not just to better antivenoms, but to universal ones.

And here’s how. [♪ INTRO] The way we make antivenoms hasn’t changed much since they were developed at the tail end of the 19th century. And considering about 100,000 people a year die from venomous snake bites, you’d think an upgrade was in order. The premise behind antivenoms is similar to vaccines, and antivenom is made is the same way early vaccines were made.

When a foreign object, like a toxin or virus, enters the body, the immune system produces antibodies that stick to it and signal other immune cells to come attack and neutralize the threat. Scientists figured out that livestock, like horses, are big enough and have strong enough immune systems that they can handle being injected with a little bit of venom. You know, as a treat.

Their bodies make antibodies to fight off the toxins. Now, it’s important to understand that “a” venom isn’t just one thing. Venom contains a lot of different things all working at once to incapacitate the snake bite victim.

We’re talking multiple toxins made by different genes or even gene families. This means that when a horse receives a dose of venom, its body is making a lot of different antibodies all at once that are trying to stick to all of the different things in the venom. Meaning its body produces a mixture of antibodies capable of sticking to lots of different things, a mishmash referred to as polyclonal antibodies.

Researchers had to figure out how to isolate these antibodies in the animal’s blood, purify the solution, and turn it into a treatment that can be injected into humans. But the problem is that the antibodies produced by the horse are only good for that specific type of snake, because the genes that produce venoms vary widely among snake species. For example, you can’t use the antibodies produced from rattlesnake venom to treat someone suffering from a black mamba bite.

In addition, there’s no way to tell the horse’s body to make an equal number of antibodies to fight every part of the venom, or more antibodies to fight off the worst parts of the venom, so antivenoms are often a bit lopsided. In fact, they’re often missing antibodies capable of attacking some of the most dangerous elements found in venom, because these components don’t tend to trigger a strong immune system response. On top of all that, antivenoms can cause pretty severe allergic reactions in people, since they’re made from the blood of animals.

So scientists have been working on making better antivenoms. Ones that can specifically attack the most toxic bits of the venom and play nicer with human immune systems. The trick here is that you can’t really go around inoculating humans with snake venom and isolating the antibodies produced.

And even if they could, it might not produce any better of a result than the horse option. Instead, researchers start in the lab, isolating the best, stickiest antibodies, including those that want to stick to the most harmful components of a given venom. And the best types of antibodies for the job are known as monoclonal antibodies.

This refers to an antibody made from a single gene, so that scientists can produce it in a lab to stick to one very specific thing. So instead of dosing a horse with venom and hoping for the best, lab-produced antibodies can be designed to be very targeted and very consistent. But… isn’t that a disadvantage when it comes to venoms?

Like I said, a venom is a lot of things. So having an antivenom stick to one thing isn’t what we want. Unless researchers can take those monoclonal antibodies to the next level.

Instead of just sticking to that one toxin really well, it’s possible to create monoclonal antibodies that can bind tightly to toxins that are in the same family and share similar features. These are called broadly-neutralizing monoclonal antibodies. The biggest helper in identifying these super antibodies has been something called phage display.

This allows researchers to sift through a massive collection of genes for human antibodies in order to determine which ones will bind the best to the toxins found in snake venom. To do this, researchers take those antibody genes and insert them into viruses called phages. These are viruses that normally infect bacteria, and have been a favorite laboratory tool for decades.

The phages take this genetic code and create an antibody snippet that they display on their surface. Then, the phages are exposed to the target component researchers want to neutralize – in this case, a particular toxin found in venom. The phages with the stickiest antibodies will stick to the toxins best.

So researchers can pull those out and say hey, this gene is the best, let’s go back and use it to make a proper antibody. However, that, by itself, would only stick to one part of one venom. And you could do it this way, by making a bunch of these for every component in a venom and mixing them together, but that’s so labor-intensive compared to the horse thing that it’s not really worth it.

Luckily, this is where the clever part comes in. Because researchers can then take another toxin, with similar features, and go through the whole song and dance again. So they can find an antibody that sticks to two, three, four toxins… and so on.

That means researchers can hone in on one or two broadly neutralizing antibodies capable of tackling an entire family of toxins in venom. For example, the authors of a Nature Communications paper published in 2023 used this technology to identify one antibody out of over 700 potential candidates. They found one antibody that was particularly good at neutralizing alpha-neurotoxins found in the venom of several deadly snake species around the world… including king cobras and black mambas.

Thanks to the advantages of producing monoclonal antibodies, this could lead to an antivenom that works against all of those guys, from one gene. It’s a step up from horses, if you ask me. Ok, ok, maybe I’m beating a dead horse here.

But broadly neutralizing antibodies are taking the risk and the luck out of making antivenoms. Researchers hope these standardized antivenoms are the future of snake bite care, and because the process is so consistent, they believe such treatments will be more cost effective and easier to produce. They envision something that’s available worldwide for anyone to have on hand when they need it most – an ideal situation for people who live near the deadliest snake species or in remote regions, that otherwise might not survive a snake bite.

And no livestock required! After all, livestock just take up so much space; space we could be using to grow more coffee, because there’s over 450 different coffees offered by Trade Coffee alone! Trade connects you to over 55 roasters in the US, so whether you like dark roasts, espresso, blends, or rare roasts, you can find it at Trade Coffee.

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It’s comforting, rich, and low in acidity. To try it for yourself, you can go to drinktrade.com/scishowoffer to get a free bag of coffee with any subscription purchase. Thank you to Trade Coffee for supporting this episode of SciShow. [♪ OUTRO]