Health and Healthcare Systems

Why this sea creature is still a key ingredient in testing vaccines

An Atlantic horseshoe crab moves across the sand on Pickering beach, a national horseshoe crab sanctuary in Little Creek, Delaware, May 20, 2008. The Atlantic horseshoe crab, part of the Atlantic coast ecosystem and an ancient species more than 350million years old, return from deeper water each May and June to lay their eggs on these beaches at the new and full moon tides. During spawning the crabs form clusters along the water's edge with as many as 12 sattelite males grouped around one female. The females burrow into the sand to lay masses of green eggs which are fetilized by the males. The eggs provide essential food for as many as one million migrating shore birds that use horseshoe crab eggs as their primay food source on their northward migration.  REUTERS/Mike Segar  (UNITED STATES) - PM1E45S0SJ101

There are about 400 coronavirus drugs and vaccines in development, all need to be tested using horseshoe crab blood. Image: REUTERS/Mike Segar

David Elliott
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  • For decades, horseshoe crab blood has been instrumental in making sure vaccines are safe.
  • Calls for a man-made alternative to be used have been dealt a blow by an influential US standards group.
  • All injectable medicines, including any potential COVID-19 vaccine, must be tested for harmful endotoxins.

The milky-blue blood of an invertebrate older than the dinosaurs might not be front of your mind when rolling up your sleeve for an injection.

Have you read?

So it may come as a surprise to learn this exact ingredient is instrumental in the testing of vaccines around the world.

Hundreds of thousands of horseshoe crabs are caught for this purpose every year in fact. And while the miracle work of these creatures might usually fly under the radar, it has hit the headlines as the race to find a COVID-19 vaccine ramps up.

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.

The number of coronavirus drugs and vaccines in development worldwide. Image: Statista

Living fossils

Horseshoe crabs are commonly fished off the East Coast of the United States for use in medicine.

They’re not actually crabs, rather arthropods more closely related to scorpions, and they have existed nearly unchanged for more than 440 million years. Due to this ancient lineage, they are often referred to as “living fossils”.

One of the reasons the species has survived for so long lies in that blue blood, so coloured because it’s rich with copper. It clots when it encounters bacteria, making it both a lifesaver to the horseshoe crab and essential to human medicine today.


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Crucial test

Since the late 1970s, the clotting agent in the Atlantic horseshoe crab’s blood has been used for the limulus amebocyte lysate (LAL) test, which detects bacterial endotoxins in drugs and intravenous devices. This kind of contamination could be harmful and even fatal to patients if it gets into the bloodstream.

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 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.

Synthetic alternative

Wildlife groups worried about these impacts have called for a man-made alternative – recombinant Factor C (rFC) – to be used instead of LAL.

The organization that issues quality standards for such tests in the States, US Pharmacopeia (USP), says rFC is more sustainable because it can be made in unlimited quantities.

But USP also believes more data is needed before it can give the new test and LAL equal status – something that Europe is moving to do. Which means that, for now, as Reuters reports, horseshoe crabs’ blood will remain the drug industry standard.

Blue gold

About 70 million endotoxin tests are performed annually in a roughly $1 billion market. And the horseshoe crab blood currently so essential to its operation is thought to be worth about $16,000 dollars a litre, according to Bloomberg – no wonder it’s sometimes referred to as blue gold.

In the coming months, and until a man-made alternative becomes more established, it could be worth its weight if it helps scientists deliver the billions of doses of a COVID-19 vaccine that will be needed around the world.

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