Long before dinosaurs roamed the Earth, peculiar creatures abandoned their journeys across the ocean floor. They resembled beings adorned with spiked helmets and had eyes positioned on top, along with sharp tails extending behind them.
Today, horseshoe crabs still exist and belong to the animal order known as Xiphosura, derived from ancient Greek, meaning “sword” and “tail.” Despite their name, they are more closely related to spiders than to crustaceans.
Fossils of horseshoe crabs date back to the Upper Ordovician period, approximately 450 million years ago. Their descendants—four existing species—have undergone significant changes in appearance, earning them the title of “living fossils.”
Despite their ancient lineage, horseshoe crabs are crucial in today’s world. Most people eventually come into contact with life-saving doses of bright blue blood derived from these creatures.
The blue hue comes from Hemocyanin, a pigment responsible for oxygen transport, which is analogous to red hemoglobin found in vertebrate blood.
Importantly, it also harbors their blood. Amebocytes, a powerful immune cell are exceptionally sensitive to harmful toxins produced by bacteria. Endotoxins, prevalent in the environment, are resistant to standard sterilization methods.
Should a vaccine contain endotoxins, it could trigger a dangerous reaction historically known as “injection fever.”
Previously, tests were conducted by injecting a vaccine batch into a living rabbit; if any exhibited a fever, it signified contamination.
In the 1960s, American marine biologists observed that the blue blood of horseshoe crabs coagulated instantly upon contact with fever-inducing endotoxin. This mechanism allows horseshoe crabs to encapsulate bacteria by forming clots around them, proving beneficial for human applications.
Now, rather than injecting rabbits, hundreds of thousands of horseshoe crabs are harvested from the ocean each year, with a third of their blood extracted to test for endotoxins in intravenous medications and medical implants.
The demand for blue blood has surged, especially with the competition surrounding the development of the COVID-19 vaccine.
Not all horseshoe crabs survive the blood collection process; approximately 15-30% do not. Conservationists are advocating for synthetic alternatives to blood tests.
In the 1990s, researchers in Singapore developed a method to create synthetic endotoxin detection using a compound based on horseshoe crab DNA. Currently, various alternative compounds mimic this reaction without utilizing horseshoe crab blood.
Although regulatory processes have been sluggish, these new compounds received approval for use in Europe in 2016 and 2024. Nowadays, pharmaceutical companies are increasingly opting for synthetic methods.
This development bodes well not just for horseshoe crabs but also for other species reliant on them. Each year, thousands of horseshoe crabs come ashore on sandy beaches along North America’s East Coast, particularly in Delaware Bay, where eggs are laid near Philadelphia.
A single female lays around 4,000 eggs, many of which become vital sustenance for migratory birds like the red knot, which journey between South America and the Canadian Arctic.
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