• Parise Lockwood

Horseshoe crabs; the backbone of the biotech industry

Have you ever heard of horseshoe crabs? The majority haven’t and yet you have almost certainly benefited from this creature within your lifetime. In fact, every vaccination, surgery or medical test that you have received recently has been impacted by horseshoe crabs.  

Horseshoe crabs are one of the oldest species on this planet. Having been around for over 450 million years, they have lived alongside the dinosaurs and survived several mass extinctions, however, since 1977 they have been exploited by the pharmaceutical industries for one specific factor. 

Their blood is one of the world’s most precious resources costing around $15,000 for one quart (0.95L for ~£11,430)

But what makes this blood so different to others? 

Image credit: green queen

Like all species, horseshoe crabs have an immune system to help detect harmful pathogens. However, due to them having an open circulatory system it has adapted to be particularly sensitive to avoid infection spreading through itself. 

This blue blood contains the only natural source of limulus amebocyte lysate (LAL) which is incredibly sensitive to bacterial toxins and is used by pharmaceutical companies to detect contamination during the production of any vaccine, implanted medical device or IV drip. When LAL comes in contact with bacterial toxins, it forms a gel-like capsule around it preventing it from further contamination within the body. Before the use of horseshoe crab’s blood, patients were at risk of saline fever potentially resulting in septic shock and fatality.

Prior to the discovery of LAL, rabbits would be injected with samples of the vaccination and observed to see if there was an adverse reaction towards it. In 1997, the FDA allowed LAL kits to replace rabbits and the rest was history. Nowadays, you simply add LAL to a part of your sample and if clotting occurs, bacterial toxins are present. It is a lot more convenient and effective than the injection of hundreds of rabbits. 

Around 400,000 horseshoe crabs are bled every year for medical uses with around 30% of blood being removed from each crab before being thrown back into the sea. There is no confirmed evidence of the long-term implications of milking the crabs in this way. It has been estimated that anywhere between 10-30% of harvested horseshoe crabs die within the first two weeks of being returned to the sea, with those that survive being at a higher risk of becoming infertile. 

This is not sustainable. If we continue to exploit this resource, it will soon disappear along with all the health benefits and lives it has saved. 

Fortunately, a synthetic version of LAL has been produced. Professor Ding isolated the clotting enzyme, factor C, from LAL. She first tried to implement the gene which produces factor C into yeast cells with little success before injecting baculoviruses with factor C into insects. As insects and horseshoe crabs share similar evolutionary lineages; it was a success.

Although there was little interest in factor C kits at first, eventually regulatory bodies, such as European Pharmacopeia, recognised it as an official bacterial toxin test. Gradually, increasing numbers of research companies have been adopting the factor C kits which will hopefully start to reduce the direct need of these vulnerable crabs. 

In my opinion, Horseshoe crabs are the unsung hero of the last century and have provided a resource that has helped us immensely and now, with the advances that we have made in biotech, we can continue to benefit from them in a more sustainable way. 

Image credit; wetlands institute

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