So, who donates this primary ingredient for medical research and the development of vaccines? Dr Anjani Ganase discusses our connections to the ancient horseshoe crab.
The horseshoe crab – if I want to be overly dramatic – is the most alien creature that I have ever come across. During my first year studying in Florida, we observed the gathering of horseshoe crabs along the water’s edge of a beach. From above, this crab looks like a mobile helmet without a body crawling slowly across; turn it over and, the wriggling legs around a mouth gives the appearance of a baby alien. Sometimes there is a micro biome of worms and other critters that infest the underside of the horseshoe crab.
The horseshoe crab is actually not a crab. Rather, it is a close relative of spiders and scorpions. There are four species existing today; one species, the Atlantic horseshoe crab (Limulus polyphemus), can be found along the eastern coast of USA and along Mexico. The other three species are found in different parts of Asia, including India, China and Japan. The horseshoe crab has been around for about 445 million years, surviving without further evolutionary adaptation. To put it in perspective, back then the ocean was dominated by invertebrates, Pangaea the super continent was yet to break apart and there would be another 215 million years until dinosaurs appeared on the scene.
The ecology of the horseshoe crab is also bizarre. They are omnivores that feed on snails, small crustaceans, and bivalves (barnacles, mussels), as well as algae. While they don’t have teeth, they use their ten powerful legs to break apart the prey before feeding itself bite-sized pieces. They mate and spawn along the shallow bays but then relocate to the deeper sandy areas to live and forage. The spawning event draws hundreds of horseshoe crabs to the sandy shores, where each female horseshoe crab might lay up to 88,000 eggs in a season. The amount of eggs laid, makes the spawning an important ecological event as many fish species and birds align their migration cycles with this spawning activity for feeding. There are few predators of adult horseshoe crabs apart from humans, sharks and loggerhead turtles.
One of the main reasons for their survival is their blood. The blood of the horseshoe crab is copper-based (haemocyanin) which runs clear in the body but turns deep blue when it gets oxygenated. The blood also contains a chemical compound called Limulus Amebocyte Lysate (LAL) that plays a major role in the horseshoe crab’s defence against bacterial infections, and likely the reason for such successful survival of the species. The compound binds to the surface of bacteria and coagulates around the bacteria, thus isolating it and allowing the white blood cells to consume it. The discovery of this was huge for biomedicine; it allowed us to develop the Limulus test which is a rapid test for contamination by bacteria in most medicines, injectable drugs, medical equipment and will undoubtedly be used in the vaccinations against covid19. This discovery dramatically improved the safety of our pharmaceutical industry. Next time you have to take an injection, you can quietly thank the horseshoe crab for not getting injection fever.
If you ever have the opportunity to view a horseshoe crab spawning event, you may observe a number of persons making their way through the chaos to select horseshoe crabs for blue blood harvesting. The horseshoe crabs are usually taken to a nearby facility where they are hooked up and drained of up to thirty percent of their blood. The crabs are then returned to the spawning area. The blood is then taken for further processing.
While the horseshoe crabs are returned to the nesting sites alive, it is still debated how many crabs actually survive the ordeal of being captured, transported out of water and drained of blood. A low estimate is about 10 per cent loss, but studies show higher mortality rates of over 30 per cent, especially in females. While some females may survive, their spawning success may actually go down with behavioral changes – lethargy and disorientation – for weeks after. The increasing demand for the blood may also impact the capture quota and the handling care. Such carelessness has decimated the population in certain areas with losses of up to 50,000 a year. However, this is not the only threat to horseshoe crabs, as more and more coastal areas become developed, removing and fragmenting the natural shorelines necessary for mating and spawning.
Strict regulations around their capture for medical purposes means nothing if the habitat is lost. Loss of habitat in the USA, as well as Asia, has led to significant decline in the horseshoe crab populations. In some places in Asia, the horseshoe crab has become locally extinct. Horseshoe crabs are also harvested for bait in the USA and food in Asia.
Although scientists have successfully created a synthetic version of the chemical compound over 15 years ago, yet the practice of blue blood harvest continues to this day. Nevertheless, pharmaceutical companies are slowly shifting to synthetic processing of LAL as a suitable alternative and as more regulations are put to conserve these creatures. We may eventually end the annual blue blood harvest of horseshoe crabs. Surely, there is an obligation to protect this ancient species by protecting the habitat, and the ecosystems – on land and in the ocean – that have allowed it to survive. In the meantime, at the very least, regulations for the harvesting process need to be improved.
Krisfalusi-Gannon, Jordan, et al. "The role of horseshoe crabs in the biomedical industry and recent trends impacting species sustainability." Frontiers in Marine Science 5 (2018): 185.
Zhang, S. (2018) The Last Days of the Blue-Blood Harvest, https://www.theatlantic.com/science/archive/2018/05/blood-in-the-water/559229/