That’s some powerful blood!

Today, I’m going to write about something that I’m certain has directly impacted every single person who reads this entry – and yet I’d bet that no one has ever heard about it. This is a story about how a simple, uninspiring-looking animal with prehistoric roots has become essential to the world’s modern medical field. This ungainly creature is directly involved in proving the safety of injectable medicines; in fact, no medicine can be injected into a single patient in the US without first being tested against the blood of this animal. And it might surprise you to learn exactly what animal I’m talking about. It’s not the rabbit. It’s not the rat. It’s not even the mouse.

It’s the North American horseshoe crab.

I’ve never seen a horseshoe crab in person. In fact, I learned about this topic myself recently from a Nova special on PBS, and what first got me watching the show was the sight of these really odd, lumpy-looking critters on a beach on Delaware. My first thought was – “what on earth is that thing on the beach? It looks like an old army helmet.” The show was fascinating, however, and I learned how amazing – and important – these creatures really are.

So what is a horseshoe crab?

Horseshoe crabs are arthropods, more closely related to spiders, ticks and scorpions than to other crabs. They are aquatic, and the North American species is mostly found in the Gulf of Mexico and along the eastern shore of the North America. (There are other related species off the coasts of Japan and India.) Their bodies are shaped like teardrops, with a long tail coming off the tapered end. They have a large intestinal system, a nervous system with a bulbous brain, and a long heart that extends almost the entire length of its body. They have numerous appendages, including legs for walking, pincers (or chelicerae) for putting food in its mouth, and book gills, which are used both for breathing and for propulsion under water. Their bodies are covered with a hard, curved shell (or carapace). This shell protects the crab from predators, who have a hard time turning them over to get at their soft, edible underbellies. (It’s also this shell that makes them look like army helmets when they’re on the beach.) Their tails serve several purposes, including working as a rudder to help steer the crab when swimming and to help flip the crab over if it gets turned upside-down while out of the water.

Horseshoe crabs have an amazing optical system. They have 2 compound lateral eyes, which are mostly used to find mates. They have 5 additional eyes on the top of their shells, some sensitive to visible light and other sensitive to UV. They have 2 more eyes on their undersides, located near the mouth, which may help keep the animals oriented while swimming. And if that weren’t enough, they also have photoreceptors along their tails to help coordinate their circadian rhythms. Phew! That’s a lot of eyes for one animal.

Where this critter really gets interesting is when you start talking about its blood. Back in the 1960s, Dr. Frederik Bang of Johns Hopkins University was studying horseshoe crabs in Massachusetts. He found that when common marine bacteria were injected into the bloodstream of the horseshoe crab, their blood immediately began to massively clot. While horseshoe crabs lack a sophisticated immune system, they do have a simple way of preventing infections from bacteria, fungus and viruses. Their blood contains numerous compounds that bind to and inactivate the toxic components of such invaders. In the case of bacteria, that toxic component is called endotoxin; the amebocytes bind to any endotoxin and coagulate around it, forming a thick, dense clot. This serves 2 purposes – first, the endotoxin can no longer harm the crab, and second, the entry point by which the bacteria got into the crab is sealed. It’s a simple, but extremely effective, mechanism of preventing bacterial infection.

And this is where the horseshoe crab and modern medicine meet. It turns out that you can purify the compounds in the crab’s blood that cause it to clot in the presence of endotoxin. So let’s say you have an injectable medicine, and you need to test whether or not it is pure – free from bacterial contamination. You mix the medicine with some horseshoe crab blood and watch to see whether a clot forms. If nothing happens, the medicine is clean. However, if a clot does form, that means there is endotoxin – and thus bacteria – in the medicine. And that means it cannot be injected into human patients. All injectable medicines in the US – including vaccines – must be tested against horseshoe crab blood before they are used. This makes horseshoe crab blood extremely valuable. It’s estimated that a quart of the stuff is worth $15,000!

The good news is that we don’t have to kill the crabs to get their blood. They are collected from the water and taken to a designated facility, where some of their blood is removed. In fact, up to 30% of the blood volume from a crab can be removed at any one time without injuring it. Once the collection is done, the crabs are returned to the ocean. Once home, they recover their lost blood volume within a week. Crabs are only bled once a year, and studies have shown that crabs can be harvested year after year without any ill effect to their lifespan or breeding habits.

I think it’s amazing that I’ve never even heard of this before I saw this Nova special. Horseshoe crabs are really important animals! And now that I know a little more about them, I guess they don’t look that strange. In fact, I’ll consider myself lucky if I ever see one in person.

The image of the horseshoe crab was taken from:
http://scienceblogs.com/grrlscientist/2007/06/delaware_horseshoe_crab_harves.php