How Horseshoe Crabs Save Our Lives
References to nobility or policemen aside, blue blood does actually exist—in horseshoe crabs. The oxygen-carrying protein in their blood contains copper rather than iron, making their blood blue. These animals have been around for 450 million years, since well before the dinosaurs, and have survived five planetwide extinction events. In 1956, Woods Hole pathobiologist Fred Bang found that certain types of bacteria caused horseshoe crab blood to clot into stringy masses. He hypothesized that this was an ancient form of immune defense, since horseshoe crabs are very disease resistant and can survive extreme physical damage. The clot formation was traced to a type of blood cell called an amoebocyte which detects the presence of potentially lethal endotoxins within bacteria.
In the 1940s, the pharmaceutical industry began to test its products for the presence of endotoxins which can be released by accident during the drug manufacturing process. Initially, companies used a time-consuming and controversial test using rabbits. But since the early 1970s, amoebocyte lysate from horseshoe crabs has been the standard test. Not only is it used for pharmaceuticals and vaccines, it also works on devices such as catheters and syringes.
The demand for horseshoe crab blood has skyrocketed in recent years, especially with the emergence of personalized cell and gene therapies. The Atlantic horseshoe crab is the primary species meeting the worldwide demand. While the crabs aren’t killed to obtain their blood, they’re captured when they come to shore to breed and trucked to labs to have one-third of their blood removed. Anywhere from 15% to 30% of the crabs die during the process. Additionally, bled crabs are lethargic for several weeks after the bleeding, preventing some from breeding. As a result, the population of horseshoe crabs is declining.
A synthetic alternative to amoebocyte lysate has been developed. The FDA allows drug companies to swap in the synthetic, known as recombinant factor C (rFC), on a case-by-case basis if evidence shows that the results are comparable to the crab-sourced material. However, the additional validation increases drug companies’ costs and time to market on new product introductions, so only a few have switched over to rFC to ensure the safety of their products.
While horseshoe crabs are still being so heavily relied upon, we could improve their fate by practicing more sustainable bleeding methods. Captured crabs are held in crowded containment ponds, without food, before having their blood removed. A recent experiment in giving them nutrients before returning them to the wild showed an improvement in oxygen flow, though not all the way to the pre-bleeding baseline. Just as human blood donors are given juice and cookies after their blood draw, rejuvenating the crabs seems a small price to pay for their life-saving service. Especially since their blood sells for $60,000 per gallon!