Horseshoe Crabs and the Medical Uses of their Blood

by Imogen B

Horseshoe crabs have existed for around 450 million years, making them evolutionarily older than dinosaurs, amphibians, and even trees. Despite how long they have been on this earth, they have physically changed very little, granting them the nickname of being a “living fossil”. Today only 4 species of horseshoe crab remain, with 3 being found on the Atlantic coast of Asia and 1 along the North American west coast. They are in fact a species of aquatic arachnid, making them more closely related to ticks, spiders and mites than true crabs. Their aquatic habitat is the result of a secondary shift back to the marine environment after the ancestor for all arachnids had changed to living on land. Horseshoe crabs are closely related, and may even be sister groups, to eurypterids, who are more commonly known as sea scorpions. Sea scorpions were the largest aquatic arthropods, being beaten by the terrestrial arthropleura for the title  of the largest arthropod. Horseshoe crabs inhabit the Atlantic Ocean. They can also swim and typically do so with their shells face-down and tilted at a 30 degree angle as they are propelled by their many legs at a pace of 10-15 cm/s. They have 2 compound primary eyes and 5 simple secondary eyes across their carapace, another 2 simple eyes are located on their underside.

As a result of branching off relatively early from the phylogenetic tree, many members of the subphylum chelicerata boast the notable trait of having blue blood. No, royalty is not what gives horseshoe crabs their blue blood, but rather a protein called haemocyanin. Similar to haemoglobin in human blood, haemocyanin serves the purpose of transporting gases around the body of horseshoe crabs. However, whilst haemoglobin is red due to the presence of iron, haemocyanin is blue due to the presence of copper. Not only is the colour of horseshoe crab blood remarkable, but its medical uses as well, as there is a good chance that your health has benefitted from a LAL test. 

The blood of some chelicerates, molluscs, sponges, and other invertebrates contain cells called amebocytes which function similarly to white blood cells in the blood of vertebrates when defending against pathogens. In the blood of Atlantic horseshoe crabs these amebocytes are used to produce LAL, which stands for Limulus amebocyte lysate. LAL reacts with bacteria endotoxins, which are present in the capsule of gram-negative bacteria. These bacteria can cause sepsis and septic shock due to their endotoxins. Thus it is important that medical equipment be devoid of such endotoxins to reduce harm to the patient. Gram stains are used on medical equipment to detect the bacteria. However, this test does not detect the presence of the endotoxins. This is when LAL comes in to test specifically for these endotoxins. 

Amebocytes are particularly helpful to horseshoe crabs as they have open circulatory systems. Rather than being contained within blood vessels, their blood flows freely in their body cavity. This allows for potential bloodborne pathogens to spread quickly throughout their bodies. Hence, it is beneficial to them to have cells that are especially sensitive to endotoxins, which their amebocytes are. 

Horseshoe crabs swarm to the shores of the Atlantic coast in late spring, particularly during a full moon, in order to lay their eggs. A female horseshoe crab may lay up to 20 batches of 4,000 eggs during her yearly beach visit. When the horseshoe crabs come ashore, many are collected by humans for the purpose of harvesting their blood. After this, they are returned to the sea. Despite being such a prevalent species in evolutionary history, they are remarkably enigmatic in that we have little luck in finding large quantities of them in the ocean. The only time it is possible to see many of them in the same place is when they come to beaches to lay their eggs. It will be another 10 years until the same horseshoe crabs who were laid return to these beaches once they have reached sexual maturity.

Despite thriving through multiple mass extinction events, the biggest threat to horseshoe crab species today is a combination of human activity. Around 15% of collected horseshoe crabs die during the blood harvest. It has also been found that fewer horseshoe crabs are returning to frequently harvested sites. In addition to harvesting, horseshoe crabs are also threatened by coastal development, which deprives them of a location to spawn. They are also killed to be used as fishing bait. However, there is hope for horseshoe crabs. Researchers are hoping to develop a synthetic alternative to horseshoe crab blood in order to conserve this timeless species. Until then, however, their blood will be instrumental in ensuring the safety of people receiving medical treatment.