Around 248 million years ago, a mass extinction wipes out most life on Earth. Half of all animal families become extinct. Almost every single marine species is erased, including thousands of species of trilobite. Among the hardy survivors is a trilobite cousin, a 10-legged, 9-eyed, carapace-covered creature, living in the shallow waters of a ravaged planet.
Fast forward 200 million years, and our survivor continues to live in these shallow waters, a small creature surrounded by giant dinosaurs. When another mass extinction hits the Earth, these giants succumb, along with about half of marine invertebrates. But not our survivor, whose unchanged shape and size allow him to soldier on, even through several ice ages.
Who is this survivor, a living fossil that looks like a rock, moves like a tank, and chews food with its legs?
It is the humble horseshoe crab, a blue-blooded arthropod whose primitive immune system has given medicine a way to protect us from infection.
Who are you calling primitive?
Because the horseshoe crab has remained relatively unchanged over the past 450 million years, many of its systems are considered "primitive," that is, not as complex as those seen in animals that have gone through millions of years of evolution. Its immune system is considered primitive, but it has protected the horseshoe crab from infection for hundreds of millions of years, and now it protects us.
First, let's look at the basics of the horses crab anatomy. Under the shell-like carapace, the horseshoe crab has a body much like a crab (although it is closer related to a spider), with jointed legs and a centralized heart. This long heart pumps blood through a semi-closed circulatory system, using arteries to transport blood but also allowing blood into direct contact with tissues. Whereas our internal organs are sterile, a horseshoe crab's organs are in constant contact with blood, and as a result, any pathogen that might enter the bloodstream.
Now let's look at its blood. Horseshoe crab blood, which carries oxygen throughout the body just like ours, is made up of hemolymph, the fluid, and two types of cells, hemocytes and amebocytes. Hemocytes carry oxygen on the protein hemocyanin, a copper-based protein that gives the oxygenated blood a bright blue color (hence the "cyan" in the name). Amebocytes (named due to their amoeba-like mobility) are the horseshoe crab's immune system, releasing granules that create clots around invading pathogens.
A Preventive Test
It is this clotting response that was discovered in 1959 by a researcher who noticed that one of the horseshoe crabs he was studying, which had died from a serious infection,had semi-solid blood. Further study revealed that horseshoe crab blood coagulates in the presence of not just Gram-negative bacteria, but also the endotoxins they release, which can cause damage even if the bacteria is dead.
As a result of this discovery, it is now standard procedure to test any liquid, device, or needle for the presence of pathogens using an LAL test, or Limulus amebocyte lysate test. Blood is drawn from horseshoe crabs (whose scientific name is Limulus polyphemus), amebocytes separated by centrifuge, and placed into water until they swell and burst (they lyse), releasing the coagulating granules. Items are placed in a solution of this lysate and if the liquid coagulates, contamination is confirmed and the product is destroyed.
Any time IV fluid, tubing, needles, or intravenous medicine is used, it owes its safety to a test made possible by a 450-million-year-old creature with aqua-blue blood swimming with motile ninja cells. Pretty amazing.
Thankfully, the horseshoe crabs don't have to sacrifice their life to help ours - all the crabs are returned to the ocean after only some of their blood has been drawn. This isn't to say that horseshoe crabs are in the clear in terms of survival. These resilient creatures who have survived two mass extinctions, an asteroid, several ice ages, and millions of years, are diminishing in numbers thanks to over-harvesting. It turns out that fishermen use horseshoe crabs as bait for eels, which in turn they use as bait for fish. Strange but true.
So next time you walk on the beach and see the horseshoe crab's distinctive carapace, take a moment to consider this incredible creature and the role it plays in keeping us healthy.
