The Atlantic horseshoe crab: unsung heroes of the deep
The phrase everything comes at a price seems to stand true in nearly all aspects of life, and medical microbiology is no exception.
In 1956, Fred Bang discovered a special protein within the amebocytes (i.e., the invertebrate equivalent of white blood cells) in the blood of the Atlantic horseshoe crab (Limulus polyphemus). This protein, known as coagulogen, exists to protect the crabs from unwanted microscopic invaders. With the aid of this protein, the amebocytes can detect the presence of harmful endotoxins found in the cell walls of gram-negative bacteria, like Escherichia coli. Once the bacterial endotoxins are detected, the amebocytes will use the coagulogen to produce a gel that surrounds, and effectively disables, the toxins.
Atlantic horseshoe crabs need this special protein to effectively manage invaders due to their open circulatory system, which makes them more vulnerable to infection than organisms with a closed system. In an open circulatory system, blood flows freely throughout the body without the guidance of veins and as a result comes in direct contact with body tissues. This feature makes the crabs more susceptible to their systems becoming overtaken by harmful bacteria, as they lack pathways to contain the infection.
You may be thinking, this is great for the crabs but how does this relate to human medicine? Well, a big concern in medicine today is the potential of medical equipment, implants, and medicines to become contaminated by bacteria prior to coming in contact with human blood, which could cause patients to become ill, and possibly even die if left unchecked. Prior to Bang’s discovery in 1956, medical practitioners could test for the presence of gram-negative bacteria in these products using the gram stain test; however, this test could only identify the presence of the bacteria itself and not identify the presence of the harmful endotoxins left by the bacteria that are no longer present. At the time, the presence of endotoxins could only be determined by distributing the potentially contaminated material to a colony of rabbits and waiting to see if any ill effects emerged – this method was neither humane, cost nor time effective.
Now, practitioners everywhere use the Limulus Amebocyte Lysate (LAL) test in which a drop of extracted Atlantic horseshoe crab blood is used to determine if endotoxins are present based on the formation, or lack there of, of gel clots. In terms of the advancement of medical microbiology, the development of this test was crucial. Nearly anyone that has received a vaccine in the last ten years can say that they have been protected by horseshoe crab blood. Additionally, these advancements have not only occurred along the Atlantic coast. While the LAL test is unique to the Atlantic horseshoe crab, other tests like the Tachypleus Amebocyte Lysate (TAL) test uses the blood of Asian species of horseshoe crabs to perform the same role in medicine. The value of horseshoe crab blood for society is not easily paralleled; however, while the medical industry may presently be distracted by the excitement of an extremely profitable resource, a dark future looms for the Atlantic horseshoe crab.
The harvest of Atlantic horseshoe crab blood does not come free. Today, nearly half a million horseshoe crabs are captured during their breeding season each year, and taken back to labs to be bled of 30% of their blood. Since the medical industry is not an actual fishery, there are no legal obligations or requirements for the harvesting companies to adhere to. Voluntary reports of post-release mortality following bleeding were once estimated to be 15%, but are now believed to be closer to 30%. While the harvesting companies do not kill the crabs, they impose stressful conditions including high heat and low oxygen environments, leaving them extremely susceptible to infection upon release back to the ocean.
These practices while seemingly necessary now, are putting heavy strains on Atlantic horseshoe crab population. The blood extracted from the Atlantic horseshoe crab plays an important role in the biomedical field, but with the current extraction methods and projected increase demand for medical devices and pharmaceuticals in the upcoming years it is unknown if the populations will sustain under these conditions. In 2012, the International Union for the Conservation of Nature (IUCN) created a horseshoe crab subcommittee to monitor the status of global horseshoe crab populations in the midst of this biomedical revolution. In 2016, when it came time for status reevaluation for the Atlantic horseshoe crab, the IUCN decided to list the species as “vulnerable” - one step closer (from the 1996 listing) to the dreaded “endangered” status.
Now you may be wondering, if this is so bad for the crab populations, then why not develop a synthetic alternative? In an effort to minimize impacts on these populations, companies are working to develop synthetic alternatives for LAL, and while some successful alternatives have been made it will still take time to become mainstream. The greatest obstacle for creating a synthetic alternative is the need for FDA backing, of which the LAL test already has.
The use of horseshoe crab blood in the biomedical industry illustrates the value of observing natural systems in microbial research, but also highlights the conservation issues associated with exploiting a finite resource for the growing demands of the human population. In a perfect world, a microbiologist somewhere will find a way to replicate the job performed by the coagulogen protein found in these creatures and reduce (or remove) the demand for their exploitation. Until that time, all we can do is thank horseshoe crabs for being the best blood donors out there.
All information for this post came from the following sources:
https://www.youtube.com/watch?v=VgEbcQxFUu8
https://ed.ted.com/lessons/why-do-we-harvest-horseshoe-crab-blood-elizabeth-cox#digdeeper
http://www.horseshoecrab.org/anat/circ.html
https://www.scientificamerican.com/article/medical-labs-may-be-killing-horseshoe-crabs/
http://www.popularmechanics.com/science/health/a26038/the-blood-of-the-crab/
https://www.theatlantic.com/technology/archive/2014/02/the-blood-harvest/284078/
This blog post was written for my Environmental Microbiology class at GMU, taught by Dr. Morrow (check her out, she's AWESOME).
