We use the expression ‘blue blood’ to signify royalty. Occasionally it’s used when a well meaning but wrong person ventures the claim that human blood is blue when it’s in your veins, only turning red when you bleed.
In your veins or on your carpet, human blood rarely strays far from the range of scarlett to crimson.
But one scuttly little seafarer has blood with particularly useful properties for medical testing, and it’s the loveliest shade of blue.
Today’s Moment of Science… Levin, Bang, and the Blue Bloods (my band name).
If you’ve kept up with everything in the news about covid, you deserve a pillow fort, a valium, and the next season of The Witcher on Netflix already. One tidbit that’s popped up occasionally in discussions of vaccine safety testing has been the use of horseshoe crab blood.
So uh… how did this become a thing?
In the early 1940s, Frederick Bang, MD, was an innovator in researching applications of marine biology to medicine. His research focused on transparent animals. For his purposes, ‘transparent’ extended to all critters whose circulatory systems you could observe in action without ending the poor specimen’s life. He hoped his observations on animals could lead to new insights on human circulation.
He got a little more than he bargained for with the Limulus, aka the horseshoe crab.
The horseshoe crab is, evolutionarily speaking, old as fuck. These things are 445 million years old, give or take a few mass extinctions. They’re cold blooded and can’t raise their temperature to fight off an infection. So as Fred Bang was about to find out, they’ve developed an odd little hulk smash of an immune system.
Bang injected horseshoe crabs with various types of bacteria. Their blood clotted immediately around the bacteria at the injection site, sealing their bodies off from harm. Eventually Bang administered an injection that caused lethal widespread clotting through the crab’s entire vascular system. Testing determined that it was the first gram negative bacteria he’d injected. Even heat treated (i.e. dead) gram negative bacteria produced this reaction. This indicated to him that it could have been a reaction to a chemical component of the bacteria.
Fortuitously, his career path crossed with hematologist Dr. Jack Levin several years later. Levin was stuck by the seemingly perpetual clotting of horseshoe crab blood. He would leave a beaker of the liquid overnight only to find it entirely clotted the next day. Throwing anticoagulants at it was a futile effort. Fascinating stuff, but seemingly without use or explanation for its antics.
Bang’s findings that that gram negative bacteria caused clotting was the missing puzzle piece Levin needed. In his previous research on rabbits, Levin observed that their blood clotted when introduced to endotoxins, which are native to the cell walls of gram negative bacteria. For Levin’s next trick, he collected horseshoe crab blood into a sterile vessel that he made sure to be clear of bacterial contamination.
No clotting.
After enough of the scientific version of poking it with a stick, they concluded that extract from the horseshoe crab’s blood cells, aka amebocytes, caused the clotting. That extract is now used as an incredibly reliable way to test for bacterial contamination in a long list of pharmaceuticals, including vaccines. Approved in 1977, this is known now as Limulus amebocyte lysate (LAL) testing and can detect endotoxin bacterial contamination at concentrations lower than one part per trillion.
Annually, hundreds of thousands of horseshoe crabs are caught, some of their blood is involuntarily donated for medical testing purposes, and they’re released back into the wild. A certain percentage of them typically die from this procedure each year, and it’s unclear how their health is affected by this long term. Since 2003, alternatives like recombinant factor C have been used with a similar degree of sensitivity in testing, but the use of LAL testing has yet to be phased out.
We used to check for contamination by injecting shit into a rabbit and hoping it didn’t get too dead. This was an improvement, but eventually we can probably leave the little blue bloods alone too.
The fact that horseshoe crab’s blood is blue, though neat, has basically nothing to do with all of this. Instead of red hued hemoglobin to transport oxygen through the body, they have a copper containing molecule called hemocyanin that serves roughly the same function. That molecule is why you could be forgiven for mistaking their blood for blue raspberry kool aid just that one time, but the sixth time it gets weird.
This has been your daily Moment of Science, asserting that Vulcan blood should have been blue.
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