Name: Why Horseshoe Crab Blood Is So Valuable
Uploaded: 2021-06-09T17:14:52.000Z
Duration: 15 min 34 s
Description: Thousands of YouTube videos with English-Chinese subtitles! Now you can learn to understand native speakers, expand your vocabulary, and improve your pronunciation...

Every year hundreds of thousands  of horseshoe crabs arrive on the  

beaches of the Atlantic coast  of America to lay their eggs.  

And every year, hundreds of thousands  of horseshoe crabs are rounded up and  

brought to the lab - not to be killed, but  for their blood to be carefully extracted.

These animals, often called living fossils, are  one of the 'oldest' creatures on the planet.  

They have remained nearly unchanged since they  first appeared on earth over 450 million years  

ago. This is due to some exceptionally effective  adaptations, and genes that code for remarkable  

molecules that have allowed the horseshoe  crab to survive, just as it is, for so long.

One of these ancient compounds is the reason  that hordes of these animals are dredged up  

from the ocean, jabbed with a hypodermic  needle, and their blue blood drained,  

processed, and sold. Their blood, made blue from  a copper-based oxygen-carrying molecule, is so  

valuable that it is the basis for a multi-million  dollar pharmaceutical industry. So valuable,  

that a single liter of it goes for around $16,000  - one of the most valuable liquids on earth.

Our reliance on these animals puts  immense pressure on a fragile ecosystem,  

and so far, scientists have struggled to  recreate this compound and its effects  

in the lab. What is it about this  primitive compound that we need  

so badly, and why can we only seem  to get it from this one creature?

The American horseshoe crab (on screen: Limulus  polyphemus) is an ancient, aquatic arthropod.  

They belong to their own class of animals, called  Merostomata, and are not actually crabs. They are  

more closely related to scorpions, with their  predecessors diverging from their arachnid  

cousins around 480 million years ago. Some  recent studies even suggest they are arachnids.  

The modern horseshoe crab as we know it has  technically only been around for 20 million years,  

but some of its early relatives, like Limulus  darwini, existed around 150 million years ago,  

and look nearly indistinguishable  from today's horseshoe crabs.  

The iconic body plan has been around even longer,  emerging around 450 million years ago. The  

changes within the horseshoe crab group have been  shockingly minor in the big picture of evolution.

Here's some perspective on just how long ago  horseshoe crabs came into existence. Pangea,  

the supercontinent of the past formed 335  million years ago and began to break apart  

about 175 million years ago. The non-avian  dinosaurs emerged 245 million years ago,  

and were wiped out 66 million years ago. The earth  descended into, and emerged from, 2 completely  

different ice ages since these crabs came about.  The world has changed so much since then. And all  

the while horseshoe crabs have been here, crawling  along the seafloor, standing the test of time.

Some of the reason natural  selection has preserved them,  

pretty much as they are, is their hardy body plan.

Their hard shell, called a carapace, is an  exoskeleton so strong that only sharks or turtles  

can penetrate it. And guiding them through the  ocean depths are 9 eyes - 2 compound eyes which  

act much like our own eyes, 5 secondary simple  eyes on top of their shell which can detect UV  

light, and 2 ventral eyes located on their  underside, perhaps to help with orientation.  

Along with their complex circulatory system, 5  pairs of gills, and 12 bristled legs, evolution  

created them to be creatures extremely well  adapted to their particular environmental niche.

But beyond the physical traits that we can  observe, much of their survival is due to  

something we can't see - their incredible, but  simple immune system. It's protected them as a  

species from bacterial infection for eons. It  works in an entirely different way from ours,  

and in the late 1960s, we began to  harness its power for ourselves.

In 1968, two researchers at the  Marine Biological Laboratory in  

Massachusetts observed that blood cells  from horseshoe crabs vigorously clot in  

the presence of bacterial endotoxin.  When they published their paper,  

they had no idea that what they found would  revolutionise drug safety testing forever.

Pretty much every creature in the  world is vulnerable to bacterial  

infection - and the horseshoe crab is  no exception. Once an infection begins,  

bacteria can reproduce quickly, and many give off  toxins which damage specific tissues in the body.

Botulism, for example, is an illness caused by a  neurotoxic protein produced by a bacteria called  

Clostridium botulinum. The toxin can affect  your nerves, paralyze you, and even kill you.  

Toxins like this are called exotoxins. They  are released from live bacteria into the  

surrounding environment during an infection.  But, bacteria don't have to release these  

exotoxins in order to be dangerous. In  fact, they don't even have to be alive.

Once a bacteria is killed within the  body, they sometimes release endotoxins.  

Endotoxins are the lipid portions of  lipopolysaccharides (LPSs) that are  

part of the outer membrane of the cell wall of  some bacteria. The endotoxins are released when  

the bacteria die and the cell wall breaks apart.  This toxin is a pyrogen - a fever causing agent.  

If it gets into the bloodstream, it can  lead to septic shock, and can be deadly.

But, fighting off these types of  infections is what immune systems are for.  

Immune systems have developed  to protect all different kinds  

of organisms from foreign pathogens.  And during the course of evolution,  

two different kinds of general immune system  emerged within multicellular organisms.

Humans and many other vertebrates have adaptive  immune systems that protect us by strategically  

mounting a defense against invading bacteria.  It is activated by exposure to pathogens, and  

uses an immune memory to learn about the threat  and enhance the immune response accordingly.

But many invertebrates, including horseshoe  crabs, don't have this adaptive immunity. Instead,  

they have an innate immune system, which attacks  based on the identification of general threat.

The basis for a horseshoe crab's immune  response are cells called granular amoebocytes.  

When bacteria come into contact  with a horseshoe crab's blood,  

they trigger an enzyme cascade,  mediated by these amoebocytes,  

which causes the blood in the immediate area  of the infection to clot into a gel. The gel  

surrounds and isolates the infection from the rest  of the crab, and the pathogens are neutralized.

The clotting from granular  amoebocytes is a simple,  

but very effective way for the horseshoe  crab to defend itself from infection.  

And, as researchers began to realize in  the 1960s, it's a very effective way for  

us to detect the presence of toxins in places  where we really, really don't want them to be.

When creating injectable healthcare products  like vaccines, medical implants, and IVs, it is  

imperative that they are free of any invading  microbes. It's easy enough to sterilize the  

solutions or devices by blasting them with heat,  radiation, or gas that is deadly to bacteria.  

But killing bacteria isn't enough to make these  products safe. If certain bacteria was present  

before sterilization, the endotoxin will remain,  and can lead to severe consequences if injected.

Historically, pharmaceutical companies  got around this problem with huge colonies  

of rabbits - needed for what's  called the rabbit pyrogen test.  

To see if a product or drug is contaminated  with endotoxin, three (unlucky) rabbits would  

be injected with a small amount of the  drug or product in question and monitored  

for four hours. Rabbits have a similar pyrogen  tolerance to humans, so if any develop a fever,  

the batch would be considered to be contaminated  with bacterial endotoxin. This is an effective  

way of preventing endotoxins from accidentally  being injected into the public, but because it  

is an in-vivo test - meaning done inside a living  organism- it's very time-consuming and expensive.

So when researchers noticed the  clotting effect of the horseshoe  

crab's amoebocytes in the presence of  endotoxin, they realized it could be  

an in vitro way of spotting contamination  - a much cheaper, easier, and faster test.

This in vitro test is called the LAL test  - limulus amoebocyte lysate. Limulus being  

limulus polyphemus, the american horseshoe crab.  This test has become the worldwide standard for  

screening for bacterial contamination. It is  capable of detecting endotoxin at significantly  

lower levels than the rabbit pyrogen test.  Today, every drug certified by the FDA must  

be tested using LAL, as do surgical implants  such as pacemakers and prosthetic devices.

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Why Horseshoe Crab Blood Is So Valuable

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