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SALT LAKE CITY — Horseshoe crabs are a very ancient species, and some of their bodily systems are equally primitive, their blood and immune defenses in particular. But scientists have found a modern use for that primitive blood that has saved thousands of lives.
Horseshoe crabs are considered living fossils, says Julie Dunlap, a naturalist and author of “Extraordinary Horseshoe Crabs.” Fossils of horseshoe crabs have been found in the Ordovician Strata, roughly 450 million years old. To help put that in perspective, that’s 100 million years before dinosaurs first appeared.
The thing that makes horseshoe crabs so valuable to science, and the medical industry, is their strange blood. Unlike mammals, which transport oxygen through their bodies using hemoglobin, horseshoe crabs transport their blood using hemocyanin. The difference is that hemoglobin contains iron — it’s the iron that bonds with oxygen and carries it through the mammal’s body. A mammal’s blood is red because of the iron it contains.
A horseshoe crab’s hemocyanin uses copper in place of iron, Dunlap explains. With hemocyanin, the copper bonds with the oxygen. Copper bonds with oxygen less efficiently than does iron, but efficiently enough for the horseshoe crabs to have survived for more than 450 million years. Because their blood contains copper, rather than iron, the blood of horseshoe crabs is blue. Mollusks, some shellfish and arthropods — scorpions, spiders and ticks — also have hemocyanin, rather than hemoglobin, says Dunlap. Horseshoe crabs, despite their name, are not actually crabs. They also belong to the arthropod family.
Interesting as that may be, this isn’t what scientists like about a horseshoe crab’s blood. Their blood also contains amebocytes, which attack pathogens, bacteria, and endotoxins (the chemical poisons that bacteria make) attempting to infect the crab. Amebocytes are believed to be a precursor to white blood cells, and they work in a similar way, says Dave Grant, a naturalist at Brookdale Community College’s Ocean Institute.
When a vertebrate’s white blood cells detect invading pathogens, the white blood cells attack and destroy it. A horseshoe crab’s amebocytes detect pathogens and endotoxins, then surround it and contain it, preventing it from spreading, Grant explains. It’s this quality that scientists find useful.
Technicians use a purified extract of these amebocytes — called Limulus Amebocyte Lysate, or LAL — to test if injectable medications, vaccines or blood products, such as plasma or blood donations, are clean of bacteria and endotoxins. If the drug or blood product contains pathogens the Limulus lysate will form a jellylike clot around it, and the blood technicians will know that the drug, or blood product is contaminated, and unsafe to use.
The LAL test is used worldwide by pharmaceutical and medical device industries to ensure that their products are clean and safe for use. The LAL test can detect even microscopic amounts of pathogens.
Limulus Amebocyte Lysate can detect endotoxins as low as 0.1 parts per trillion, says John Dubczak, General Manager at Charles River, a company that manufactures Limulus Amebocyte Lysate.
Even a microscopic amount of endotoxins in a person’s bloodstream can cause dangerous fevers, or death. The ability to test drugs and blood supplies prior to being given to humans has saved countless thousands of lives, says Dunlap.
“Anything that will contact blood — either directly or indirectly — will require LAL testing, Dubczak said. “Imagine you’re visiting a friend in a hospital. Your friend is receiving IV fluids. The LAL test is used to test the solution in the bag, as well as the tubing that the fluid travels through, and the plastic cannula that has been placed into your patient’s vein.”
Limulus Amebocyte Lysate can detect gram-negative bacteria but not gram-positive bacteria, such as staph. It can also detect fungal contaminants as well.
Extracting the blood from horseshoe crabs is its own little industry. Fishermen who have permits from the Department of Natural Resources for the purpose of drawing blood from them harvest horseshoe crabs, Dubczak said. The crabs are “hand harvested,” meaning the crab harvesters must catch each crab by hand, because it’s less harmful than mechanized methods.
The fishermen transport the horseshoe crabs to a lab, where a technician bleeds part of the crab’s blood, but not so much that they die. The shell of a horseshoe crab has a hinge about two-thirds of the way back. The needle is inserted through the hinge into a blood-rich sinus beneath it, Dubczak said.
After a technician has drawn blood from a crab they are given back to the fishermen who release them back into the ocean. It’s estimated that more than 200,000 horseshoe crabs are collected and “bled” each year. There are four types of horseshoe crabs, but only the blood of one type, Limulus polyphemus, is used to make Limulus lysate.
Horseshoe crabs, though they somewhat resemble crabs, aren’t actually crabs — they’re arthropods. Their closest living relatives are scorpions, spiders and ticks. Viewed from above, a horseshoe crab looks like a discarded, brown helmet. Their entire outer surface is comprised of a thick armor of chitin, the same material that forms the exoskeletons of crustaceans, insects and other arthropods.
Like fish, horseshoe crabs breathe with gills, which are located just behind its legs. Water gets circulated to the gills by the motion of the legs. If a horseshoe crab gets stranded out of the water, it can burrow into damp sand and continue to breathe for several days, as long as the gills stay damp, Dunlap said.
Horseshoe crabs spend their entire lives burrowing through the sea mud looking for food. They only come to shore to mate, which they do between April and June. A female horseshoe crab will scoop out a bowl in the intertidal zone and deposit as many as 4,000 eggs inside it. A female will return to the beach several times during the spring to lay more eggs. A single horseshoe crab may lay as many as 100,000 eggs in a nesting season, says Dunlap. An egg is about the size of a pea.
But only one out of every 130,000 horseshoe crab eggs survives into adulthood, and in the recent decades those odds have worsened due to a number of environmental factors, Dunlap said. Horseshoe crabs live in water that is growing increasingly polluted. Many of their nesting grounds have been lost to coastal development. And every year, hundreds of thousands of them are killed for eel and conch bait.
The amazing horseshoe crab has saved thousands of human lives, and now it’s time for us to return the favor.
In recent years, horseshoe crabs being harvested for bait has become regulated, and many of their nesting grounds have been restricted from further development, says Dunlap.
But we may play an important role helping it continue its amazing journey into the future.
It’s an odd alliance where one of the world’s most ancient species and one of its latest arrivals has come together to help each other move into a healthier future.
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