During the warmer months, especially on a full moon night, several thousand horseshoe crabs emerge from the sea onto beaches across the U.S. mid-Atlantic to spawn. For pharmaceutical companies, they work as an important resource for making medicines safe. Teams of lab workers capture the horseshoe crabs and take them to labs to harvest their cerulean blood, before returning them to the sea.

The animals’ milky-blue blood is the only known natural source of limulus amebocyte lysate (LAL), a substance that detects a contaminant called endotoxin, a type of bacterial toxin. Even an iota of endotoxin in vaccines, injectable drugs and more can prove to be fatal.

According to horseshoecrab.org, “Research on horseshoe crabs showed that their blood is very sensitive to endotoxin, which is a component of Gram-negative bacteria like E. coli. In the 1960s, Frederik Bang and Jack Levin developed a test from Limulus polyphemus blood that detected the presence of endotoxin. This test, based on the fact that the blood of the horseshoe crab gels or clots when it comes in contact with endotoxin, was called the Limulus amebocyte lysate (LAL) test and was commercialized in the United States in the 1970s. In Asia, there is a similar test called TAL which takes its name from an Asian species of crab, Tachypleus tridentatus.”

Horseshoe crabs return to the sea once they hatch and only return to the shore once they reach sexual maturity, which might be a gap of a decade. The eggs laid by female horseshoe crabs, around a 100,000 eggs, also help the ecosystem as sea birds depend on them too.

“Scientists take about a third of a horseshoe crab’s blood for use in the tests, after which the creature is released back into the ocean. Companies that make LAL tests say the animals are not harmed during the procedure,” according to World Economic Forum.

“According to some estimates, though, 15% may die as a result of the process. And there’s concern the horseshoe crab is facing pressure on many fronts – it’s also fished to be used as bait and suffering due to habitat loss and rising sea levels. It has a key role in the ecosystem, too, with its eggs providing food for bird species including the threatened red knot,” adds WEF on its official website.

Living fossils

Horseshoe crabs are not actually crabs, but arthropods that are more closely related to scorpions. They have existed for more than 440 million years across eons. Due to their ancient lineage, they are often referred to as “living fossils”.

One of the key reasons of the species’ longevity is their blue blood, so coloured because of its rich copper content.

Catching these crabs and harvesting their blood is time-consuming, with the resulting lysate costing $60,000 per gallon (approximately $16,000 per litre) according to Bloomberg, giving it the name of ‘blue gold’.

Overharvesting and their use as fishing bait is causing the crab numbers to deplete at a fast pace which is alarming marine conservationists globally.

Covid-19 vaccine

As the race to find a vaccine to the deadly coronavirus ramps up, the marine creatures have hit headlines once again. “With about 400 coronavirus drugs and vaccines in development and safety tests using horseshoe crab blood currently the industry standard, this unusual-looking critter is set to play an important role in the pandemic,” says a report by World Economic Forum.

A synthetic alternative to LAL

Companies can use a synthetic alternative to the blood of horseshoe crabs in safety tests for medical products, a European agency has ruled, in a boost for wildlife advocates and groups such as Lonza that make it. To test for bacterial contamination in medical products, the world now relies on a single source of lysate – the blood of two species of the horseshoe crab family that are endangered, states a report by Reuters dated July 2.

Wildlife conservationists are pushing drugmakers to switch to a synthetic alternative for the tests, including those needed before a Covid-19 vaccine can be used on humans.

The issue in question for the agency was whether recombinant factor C (rFC) can be used in the bacterial contamination tests, rather than the classic limulus amoebocyte lysate (LAL)-based methods that rely on blood from the crabs.

“When used under appropriate conditions, rFC-based methods provide the same guarantee of a product’s compliance with the test for bacterial endotoxins – and therefore, of its safety for use in patients – as LAL-based methods,” Susanne Keitel, director of the European Directorate for the Quality of Medicines and Healthcare (EDQM), said in a statement.

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