The horseshoe crab is a living fossil that has called Earth it's home for almost half a billion years. It’s outlived dinosaurs and survived mass extinctions and ice ages, but today it’s facing a new threat.
Their adaptations have worked with the way the Earth has changed and it’s only in recent years with humans bringing impacts to their population that they have started to have declined.
Rising sea levels, habitat loss and overharvesting all threaten the population. But if you have ever had a vaccine, injection or a medical implant, then you might not know that you have been relying on this prehistoric creature’s blood to save your life. Now, after decades of waiting, a new synthetic solution could change all of that.
In May and June on the Delaware Bay, millions of crabs come out on a high tide to lay their eggs about six inches deep in the sand and they will stay in the sand and hatch in about a month. And horseshoe crab eggs are a really critical part of the ecosystem of Delaware Bay. If a single crab is laying almost 100,000 eggs, that is providing a food source for shorebirds, for gulls, for fish, for terrapins and then all up to the food chain for that. And then what happens with the horseshoe crabs then trickles down to the whole ecosystem here. They just have managed to evolve with the changing oceans and the changing land.
The reason this crab has been able to evolve for so long? Its blue blood. This copper-based blood contains special cells called amebocytes, which are extremely sensitive to endotoxins. These are contaminants released from the cell walls of harmful bacteria and they can cause life-threatening fever or toxic shock. As soon as the amebocytes detect any of these endotoxins, the blood clots around the intruder, immobilizing it and protecting the crab from infection.
In the 1960s scientists found a way to harness this unique superpower to make sure our medical supplies were free from contamination. It replaced slower, more unpredictable tests involving rabbits. The formula is called Limulus amebocyte lysate, or LAL, and relies on amebocytes taken from horseshoe crab blood.
So every year half a million crabs are collected along the Atlantic coast, as well as across the eastern shores of Mexico and China. A third of the crab’s blood is drawn before they are released back into the ocean. It’s estimated that 15% of crabs collected die as a result of this bleeding process, which could mean the loss of 75,000 crabs only in the US alone every year.
All this could change in the near future as an alternative was found. In the mid-'80s Professor, Ding Jeak Ling needed LAL for work involving IVF embryos, but there was a problem. Singapore research was not very well funded. So because the LAL was so expensive, They had to find a good way to understand how the horseshoe crab blood works. They took only a small volume of the blood, isolating the blood cells from the horseshoe crab and start to study it. Eventually, they produce a synthetic equivalent of LAL.
This synthetic equivalent is called recombinant factor C, and it’s a clone of the main gene in a horseshoe crab’s blood, which is sensitive to bacterial endotoxins. It was a moment of realization that it is going to change the biomedical industry and it's going to save a very, very highly threatened species.
But the pharmaceutical companies didn’t come around as quickly as Professor Ding had hoped. A lot of people are reluctant to take a chance on trying something new. That’s until a scientist at pharmaceutical company Eli Lilly came along.
He said, "the horseshoe crab is a keystone species in its ecology obviously for its own sake but then for a lot of other animals that depend on it. If we use RFC then there aren't any crabs that are affected, whether it's mortality or whether there's some behavioural effect by taking the blood. Studies have shown that the RFC test is a more effective and potentially cheaper solution than LAL. Changing minds, however, remained the biggest challenge."
In 2018, the first drug to use the recombinant factor C test was approved by the FDA, and Eli Lilly is planning to transition 90% of its tests to the synthetic by the end of 2020. Eli Lilly thinks that the consequence if industry carries on with bleeding crabs, is that at some point there won't be any. So there are real impacts on what he is doing.
It is important that we as humans are playing a role in protecting biodiversity and not impacting biodiversity. The synthetic version of the horseshoe crab lysate used by the pharmaceutical industry is going to have a major impact on horseshoe crab conservation. It's not the only factor that we need. We also need to continue with harvest limits and with beach restoration. But reducing the need to harvest crabs for the use of their blood will have a major impact.
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