Horseshoe crab resting on beach taken by Timothy Fadek https://www.timothyfadek.com/horseshoe-crabs
After millions of years, the splitting of the continents and 5 mass extinction events, horseshoe crabs are facing their biggest threat: humans. The extreme resilience of Limulus polyphemus has earned the species the nickname “living fossils” and for organisms that have remained relatively unchanged for 450 million years, the title suits them quite well. Unfortunately for horseshoe crabs, their resilience is not the only thing that makes them unique, their blue blood has become invaluable to humans.
In the 1950s, Woods Hole Institute began experimenting with horseshoe crab blood after scientists noticed its ability to coagulate incredibly quickly. These experiments led to the discovery of limulus amebocyte lysate (LAL), a protein solution in the blood that allowed it to detect toxins at unseen speed and clot immediately (Whitney & Crunelle, 2023). This incredible compound has become a critical part of medical testing for pharmaceutical companies developing vaccines, drugs and other medical treatments, including the COVID-19 vaccine. There have been other tests for endotoxins developed before, however none compare to the effectiveness of the LAL test. The protein’s ability to detect even a billionth of a gram of harmful toxins makes it the most efficient and effective test available (Walls & Berkson, 2003).
Horseshoe crabs bled at Charles River Laboratory taken by Timothy Fadek https://www.timothyfadek.com/horseshoe-crabs
The glaring problem with this presumed treasure trove of medical supplies is that the supply is in fact finite. In order to obtain the blood, the crabs must be captured and bled. Up to 30% if their blood can be drained within a session before the live crabs are returned to the beach. The mortality rates of this practice can range from a few crabs to more than 30% of those bled (Whitney & Crunelle, 2023). The continued exploitation of the horseshoe crab population is causing increasing concern among conservationists who worry that the effects on the population could be dire. There are guidelines for how to conduct bleeding to reduce the mortality levels and some hatcheries being opened to raise eggs that are then released into the ocean in an effort to increase the remaining stock (Pavid, 2020). Despite all these efforts, the threat to the population is still great and a more permanent solution must be adopted.
Since the red flag was raised regarding unsustainability of the draining practice, scientists have been working to produce a synthetic alternative that can be used in place of the real blood. Scientists have been able to develop a substitute by cloning the LAL protein and inserting it into insect cells that behave similar to the cells of horseshoe crabs, continued efforts have led to an even more successful alternative that turns color when in contact with toxins (Randolph, 2025). Although it will take years before the bleeding practice is phased out significantly, there are now over 10 major pharmaceutical companies who are beginning the process of shifting their labs to using the new synthetic options. There are still hurdles to overcome if humans are to undo the damage done to the horseshoe crab population; however, with the concentrated efforts and continued breakthroughs, the ancient creatures will hopefully continue to live up to their title.
References:
Horseshoe crab | defenders of wildlife. (2025, October 28). https://defenders.org/wildlife/horseshoe-crab
Pavid, Katie, Horseshoe crab blood: The miracle vaccine ingredient that’s saved millions of lives | Natural History Museum. (2020). Retrieved November 14, 2025, from https://www.nhm.ac.uk/discover/horseshoe-crab-blood-miracle-vaccine-ingredient.html
Randolph, M. (2025, October 24). Horseshoe Crab Blood has long helped us make safe medicines. Now, alternatives that spare the ancient creatures might be breaking through. Smithsonian Magezine. https://www.smithsonianmag.com/science-nature/horseshoe-crab-blood-has-long-helped-us-make-safe-medicines-now-alternatives-that-spare-the-ancient-creatures-might-be-breaking-through-180987553/
Walls, E. A.; Berkson, J. (2003). “Effects of blood extraction on horseshoe crabs (Limulus polyphemus),” Fishery Bulletin, 101(2), pp. 457-459. http://fishbull.noaa.gov/1012/22wallsf.pdf
Whitney, K; Crunelle, Horseshoe crab blood is vital for testing intravenous drugs, but new synthetic alternatives could mean pharma won’t bleed this unique species dry | Published by Journal of Health Economics and Outcomes Research. (2023) https://jheor.org/post/2199-horseshoe-crab-blood-is-vital-for-testing-intravenous-drugs-but-new-synthetic-alternatives-could-mean-pharma-won-t-bleed-this-unique-species-dry