The COVID Vaccine's Secret Ingredient

Vaccines: the technology has been a source of controversy ever since it was created by Louis Pasteur in 1798, and perhaps never more so than in the last two years. The COVID vaccine has been followed by the media and people all over the world since COVID itself entered the world stage--from its original production, testing, and distribution, to the political divides and government skepticism that followed. However, despite the intimate knowledge many have gained about the vaccine process over the course of the last couple years, there is still an interesting fact about the vaccine that most people are unaware of.

Someone receiving a COVID vaccine

Enter Limulus polyphemus, better known as the horseshoe crab--one of the most interesting creatures to ever crawl upon the Earth. Many people, especially here on the East Coast, have seen horseshoe crabs at one point or another while at the beach. Whether they are live and scuttling underfoot in the waves, or in the form of remnants of a shell washing up on the beach, catching sight of them isn't all that uncommon. They are relatively unassuming creatures, most are a dull brown color with a large, dome-shaped shell and long, pointed tail. The tail is harmless and is used to help the crabs flip themselves over if they ever get tossed upside down by a wave, not to sting people like my dad had told me as a kid. So, pretty boring, right? Wrong. This small, slightly creepy, creature is one of the oldest organisms on earth, remaining almost entirely unchanged for the last 445 million years. That is absolutely insane. Totally bonkers. That predates dinosaurs, predates trees, predates like--basically everything that isn't an amoeba! Their design is simple, but has helped them to outlive almost every other species. Makes sense that their moniker would be the "living fossil."

A cute little Atlantic horseshoe crab

Despite being called crabs, Limulus polyphemus are actually more related to scorpions and spiders than other crabs. They are arthropods, with a hard exoskeleton but no spine, and ten jointed legs they use to navigate themselves around the ocean floor and crush food before moving it to their mouths. It's kind of hard to find a creature to accurately compare them to because they are the only living species left in their phylum. 

A scary little Atlantic horseshoe crab

Every year like clockwork, these incredible little creeps flock to the beach to breed and lay eggs before returning to the ocean. They almost always come during a full or new moon, and always to the same beach with migration patterns that have lasted for hundreds of thousands of years. During late May/early June, a male will find a female in the shallows and hitch a ride on her tail to the beach. When they arrive the female will then dig small holes and lay millions of small, light blue eggs, and then the male will go through and fertilize them all. Most of the eggs will be eaten by other animals around the beach, they're a main food source for many bird species, but after about two weeks the eggs will hatch. Thousands of baby horseshoe crabs (which look exactly like the adults except without tails) will return to the water.

A handful of horseshoe crab eggs. They kinda remind me of robin eggs but in miniature. 

For the rest of the year the beaches will be deserted by the crabs, but during the month of May thousands of them all come at once and often cover beaches to the point where sand is no longer visible. One of the most popular breeding grounds is right in our backyard--the Delaware Bay. Some tourists come to see the weird sight, but there are also others waiting anxiously by to see them as well. If I asked you to take a guess at who these onlookers might be, I bet the first thing out of your mouth wouldn't be pharmacists. But low and behold, they're there. In droves. 

A whole lotta horseshoe crabs

See, horseshoe crab blood is one of the only known sources for a chemical called limulus amebocyte lysate, or LAL. LAL reacts with the endotoxin lipopolysaccharide, or LPS, which is a membrane component in gram-negative bacteria. When the amebocytes in the horseshoe blood (which is a bright blue color due to its copper base) interact with the endotoxins, it causes the blood to clot. In the wild this helps horseshoe crabs a ton because any bacteria getting into a cut on the organism will be immediately jello-ed up and isolated, halting any dangerous bacteria from entering the bloodstream. Humans rely heavily on horseshoe crab blood to create LAL for our medicinal uses. The compound is the basis for the LAL test, which is crucial to the sterilization testing that all surgical instruments, artificial body part replacements, injectable drugs, and vaccines undergo. If the LAL test isn't preformed and bacterial endotoxins go undetected, they can create an infection which can become deadly extremely fast. Since horseshoe crab blood is the only known source of LAL, without them this entire process would cease to exist, and everyone undergoing a vaccine or operation would be put at serious risk of infection and sepsis. Hence the pharmacists in Delaware Bay.

The pharmacists (or ecologists/fishermen who work for pharmaceutical companies) will come to the beaches during breeding season and capture thousands of crabs a day, putting them in transport containers to be taken to nearby processing facilities. Every year they round up half a million organisms on the East Coast alone. The crabs are then washed and sterilized, and put on a conveyor belt to have their blood sucked from them. It honestly looks like something out of a horror movie. They are hung upside down as technicians put an IV into a vein near the crab's heart, and then sit for a few hours as around 30% of their blood drips into a little bottle below. After the ordeal, around 30% of the crabs die, and the rest are returned to the ocean, through nobody really knows for sure how the crabs fare when they are released back into the wild and if the loss of blood affects them negatively or not. Some conservationists say survival rates could be improved with better treatment of the crabs, but better treatment is more expensive and pharmaceutical companies often aren't willing to pay the price.

Horseshoe crabs having their blood drained. Super weird, feels like something out of a sci-fi or horror movie or something

When the blood is all bottled up and ready to go, scientists will send it to another nearby pharmaceutical site. Some chemicals will be added to turn the blood into FDA approved LAL, which will then be put on the market at roughly $60,000 a gallon. Horseshoe crab blood ain't cheap. Although there are groups focused on finding a synthetic alternative to horseshoe blood as a source for LAL, everything they have produced so far is yet to be approved by all of the necessary groups needed for it to be considered a safe alternative for the standard, horseshoe-derived, version of LAL.

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A cute little juvenile horseshoe crab

Though the cost in crab lives may seem high, most conservationists say that the pharmaceutical industry isn't the biggest threat that horseshoe crabs face. In fact, many groups in the crab-draining industry work to pass legislation that help to preserve the crabs and their natural habitats, the most recent being laws passed in Maryland and Delaware making the use of horseshoe crabs as fishing bait illegal. But horseshoe crabs do face a great amount of danger. Every year they lose more of their precious breeding space on beaches due to erosion and human development on beaches, and ocean acidification due to climate change is causing pH levels in the Atlantic Ocean to no longer remain in the crabs' sensitive range. A more recent threat has been the intense red algal blooms that have been cropping up off the east coast from eutrophication due to human fertilizer run off.

A harmful red algal bloom in Nagasaki, Japan

During 2020, a record number of horseshoe crabs were captured to be used for sterilization of the millions of COVID vaccines being sent out around the country. Every time someone sat for their dose of the vaccine, there was a horseshoe crab's bright blue blood to thank. There was also a rather scary discovery made by a conservationist group from Maryland in 2020 during the height of COVID. It indicated that the horseshoe crab population was in severe decline, more than we had originally realized, due to habitat loss, climate change, and harvesting by pharmaceutical companies. Preserving these creatures is one of the many, many reasons climate change should be considered a top issue by legislators--it affects everything. Medicine, tourism, agriculture, the economy--quite literally everything. Nothing is left untouched by climate change, including the living fossil. Horseshoe crabs could outlast T-rexes and megalodons, meteors and volcanos, but it might not be able to outlast us. It's a pretty sobering thought.