Millions of years before dinosaurs began roaming Earth, strange-looking creatures were scuttling across the seabed. They looked like they were wearing spiked helmets, with little eyes on top and a sharp tail sticking out the back.
The horseshoe crab still exists today and belongs to an order of animals known as Xiphosura, from ancient Greek words meaning ‘sword’ and ‘tail’. Despite their name, they’re not actually crustaceans, but more closely related to spiders.
Fossilised horseshoe crabs have been found dating back to the Upper Ordovician, around 450 million years ago. Since that time, their descendants – four living species – have barely changed their appearance, and they’re often misleadingly called ‘living fossils’.
Despite their ancient origins, horseshoe crabs play an important role in the modern world. Most people have, at some point, crossed paths with a life-saving dose of the horseshoe crab’s vivid blue blood.
The blue colour comes from the oxygen-carrying pigment haemocyanin, an equivalent to the red haemoglobin in vertebrate blood.
Crucially, their blood also contains powerful immune cells called amebocytes, which are highly sensitive to dangerous toxins produced by bacteria. Endotoxins are ubiquitous in the environment and aren’t easily removed by sterilisation.
If vaccines contain endotoxins, this can lead to a potentially lethal reaction historically known as ‘injection fever’.
In the past, batches of vaccines were tested by injecting them into live rabbits. If any of them developed a fever, this showed the vaccines were contaminated.
In the 1960s, marine biologists in America noticed the horseshoe crabs’ blue blood instantly coagulated when exposed to fever-inducing endotoxins. This protects horseshoe crabs from invading bacteria by forming clots around them. And it has also proved useful for humans.
Now, instead of injecting rabbits, hundreds of thousands of live horseshoe crabs are taken from the sea every year and lined up to have up to a third of their blood drained, to use to test for endotoxins in intravenous drugs and medical implants.
Demand for blue blood recently soared amid the race to develop COVID-19 vaccines.
Not all horseshoe crabs survive this blood-letting ordeal. Around 15–30 per cent die, leading conservationists to call for the blood tests to be replaced by synthetic alternatives.
In the 1990s, researchers in Singapore developed a process for creating synthetic endotoxin-detecting compounds based on horseshoe crab DNA. There are now several versions of the replacement compound that mimic the reaction without using any horseshoe crab blood.
Regulators were slow, but the new compounds were approved for use in Europe in 2016 and the United States in 2024. Now, pharmaceutical companies are increasingly turning to the synthetic alternatives.
This is good news, not just for horseshoe crabs, but also other species that depend on them. Each year, thousands of horseshoe crabs crawl onto sandy beaches along the east coast of North America, especially Delaware Bay near Philadelphia, to mate and lay eggs.
A single female lays around 4,000 eggs. Many will become vital food for migrating birds, such as the red knot, stopping off on their epic flights between South America and the Canadian Arctic.
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