Some of My Heroes, Snakes, Horses, and Horseshoe Crabs, Oh My!
My heroes, horses, snakes, and horseshoe crabs, oh my!
With this week's blog being open ended I just wanted to talk about some animal heroes that I think deserve some recognition!
At first, it may not be obvious how a snake, a horse, and a horseshoe crab are all connected, but I will try my best to explain.
Let's say hypothetically, I went out for a hike and come across a venomous snake, like the Eastern Massasauga Rattlesnake for example (the only venomous snake in Ontario), and I accidentally get bit (poor snake probably got spooked). I am going to need medical attention. Though not all bites from venomous snakes contain venom, on the off chance that this bite did, then I need antivenom.
What is antivenom? It was relatively recently that I learnt about how antivenom was made, and it kind of blew my mind.
Photo 1: An Eastern Massasauga Rattlesnake. If you see one, please give it space and do not harm it! (Credit: J.D. Taylor, https://www.ontario.ca/page/massasauga-rattlesnake)
It is here our journey begins with our first hero, the snake. The first step in creating antivenom requires a snake milking facility. Here, venomous snakes are taken care of, and encouraged to bite into cups, where their venom is directly collected.
Photo 2: A veterinarian comforts a horse (Credit: Colourbox).
Then enters our second hero, the horse! Once the venom is collected, a small amount of it gets injected into horses intravenously (Sheraba et al., 2023). Horses are usually selected because the snake venom does not have as great an effect on large animals as they do small ones. Horses who receive the snake venom, then have an immune response, and create antibodies to the venom, which can then be extracted from their plasma (Sheraba et al., 2023). The plasma is then processed transferring the antibody fragments into an antivenom that can be administered when emergencies happen (WHO, 2017; Sheraba et al., 2023). These antibodies are what would help save my life and fight off snake venom if I were to get bit!
During the multistep process of creating antivenom, there are many opportunities for contamination to happen (Sheraba et al., 2023; Solano et al., 2024). This is where the third hero, the horseshoe crab, comes into play. You see, horseshoe crabs have evolved to have a different kind of blood from mammals, one which is really good at coagulating against contaminants, which makes for a good tool for testing treatments like vaccines and antivenoms.
Photo 3: A horseshoe crab is crawling from the ocean onto the beach (Credit: Colourbox).
In order to obtain this resource, the horseshoe crabs are collected from their breeding grounds along the U.S. Atlantic coast, and delivered to facilities where they collect 30% of their blood, and then release them back where they were captured (Anderson et al., 2013). The horseshoe crab blood contains amoebocytes and hemocyanin (like our red blood cells) (Sheraba et al., 2023). This blood immune system is extremely good at its job; reacting to endotoxins released by bacteria, and creating clots around them (Sheraba et al., 2023; Solano et al., 2024). This ability the horseshoe crabs have in their blood make them a very valuable resource, because the pharmaceutical industry can use this method of testing (called limulus amebocyte lysate or LAL for short) on many different life saving products. When LAL is used in testing antivenom, it can detect bacterial contaminants, making sure it is safer to administer when the time comes.
The story of horseshoe crabs and their pharmaceutical use inspires me because their populations are declining, and it is not sustainable to rely on their blood (Maloney et al, 2018; Smith et al., 2020). Research is still determining if the process of collecting them is contributing to their decline, as well as habitat loss (Smith et al., 2020). However, there are new alternative methods like synthetic LAL (Maloney et al., 2018) or even AI testing of bacterial contamination (Jiang et al., 2021) reducing the reliance on using horseshoe crab blood.
There is this concept I have been reflecting on that I think really applies to the case of the horseshoe crabs. With the continued expansion of humans on this planet, it is important to think about all of the impacts we create and their consequences. To paraphrase what I once heard Robin Wall Kimmer explain during an online conference for indigenous knowledge, 4 Seasons of Learning (2025); sustainability is only with the mindset of keeping things good enough so that we can keep taking from the planet, and maybe we should instead be asking how we can give back to the planet. When will we able to transition into not using horseshoe crabs at all in the future, and help bring their populations back?
All of that being said, I think it is important to acknowledge that the animals being used in these life saving treatments should be thanked, and recognized as heroes. Animals do not have the ability to provide consent during any of these procedures (like the snakes being milked, or horses and horseshoe crabs being blood donors). Please note that the ethics behind these treatments are taken very seriously, and the reduction of any harm or stress on the animals is assumed. Though this is only a small example of the reliance we as humans have on animals we share this planet with, there are many more heroes (flora or fauna) that we have yet to bring awareness too.
Do you have any animal or plant heroes?
Also, if you are interested in learning more about how snake antivenom is made, check out this cool video:
Veritasium, (2022). How Horses save humans from snake bites. Youtube, https://www.youtube.com/watch?v=7ziWrneMYss
And more about horseshoe crabs blood:
Ted-Ed, (2017). Why do we harvest horseshoe crab blood? - Elizabeth Cox. Youtube, https://www.youtube.com/watch?v=VgEbcQxFUu8
Anderson, R. L., Watson, W. H., & Chabot, C. C. (2013). Sub-lethal behavioral and physiological effects of the biomedical bleeding process on the American horseshoe crab, Limulus polyphemus. The Biological Bulletin (Lancaster), 225(3), 137–151.
Jiang, S., Noh, J., Park, C., Smith, A. D., Abbott, N. L., & Zavala, V. M. (2021). Using machine learning and liquid crystal droplets to identify and quantify endotoxins from different bacterial species. Analyst (London), 146(4), 1224–1233. https://doi.org/10.1039/d0an02220a
Maloney, T., Phelan, R., & Simmons, N. (2018). Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood for endotoxin detection. PLoS Biology, 16(10), e2006607–e2006607. https://doi.org/10.1371/journal.pbio.2006607
Sheraba, N. S., Hesham, A., Fawzy, M., Diab, E., Basuony, M. E., Yassin, A. S., Zedan, H. H., & Abu-Elghait, M. (2023). Advanced approaches for endotoxin detection and removal from snake antivenoms. Toxicon (Oxford), 222, 107003–107003. https://doi.org/10.1016/j.toxicon.2022.107003
Smith, D. R., Newhard, J. J., McGowan, C. P., & Butler, C. A. (2020). The Long-Term Effect of Bleeding for Limulus Amebocyte Lysate on Annual Survival and Recapture of Tagged Horseshoe Crabs. Frontiers in Marine Science, 7. https://doi.org/10.3389/fmars.2020.607668
Solano, G., Ainsworth, S., Sánchez, A., Villalta, M., Sánchez, P., Durán, G., Gutiérrez, J. M., & León, G. (2024). Analysis of commercially available snake antivenoms reveals high contents of endotoxins in some products. Toxicon X, 21, 100187–100187. https://doi.org/10.1016/j.toxcx.2024.100187
WHO Expert Committee on Biological Standardization. (2017). WHO guidelines for the production, control and regulation of snake antivenom immunoglobulins. Geneve, Switzerland. https://cdn.who.int/media/docs/default-source/biologicals/blood-products/document-migration/antivenomglrevwho_trs_1004_web_annex_5.pdf?sfvrsn=ef4b2aa5_3&download=true