Horseshoe crabs are critical to the biotech industry A new technique in aquaculture has demonstrated a promising ability to improve survival rates, health, and performance of horseshoe crabs harvested for the biomedical industry.

The Atlantic Horseshoe crab is a 500-million-year-old species with ten eyes, six pairs of legs, and one body full of blue blood. Even though it sounds like this creature was pulled straight out of a science fiction novel, the horseshoe crab plays an integral role in the modern biomedical industry.

Horseshoe crab blood gets its striking blue color from hemocyanin, a copper-containing molecule. However, it is not the color of blood that makes the horseshoe crab important. It’s what the blood contains.

The ancient horseshoe crab has an open circulatory system, one wherein blood freely interacts with tissues. This system gives any pathogen entering the bloodstream the potential to access essential organs. To thwart this catastrophe in the making, horseshoe crabs have evolved a wicked first response team: the amebocytes.

Amebocytes are a horseshoe crab’s only type of blood cell. As such, they act as an army of one- transporting material, healing wounds, and ingesting cellular waste. But what is perhaps their most important function (to humans and horseshoe crabs alike) is their ability to produce Limulus Amebocyte Lysate (LAL).

Amebocyte lysate is a concentrated fluid that is extremely sensitive to pathogens. It can react to a contaminant concentration on the order of one part per trillion. Upon detection, the lysate rapidly forms clots that trap pathogens in a gel-like substance, thereby limiting further infection. Specifically, amebocyte lysate solidifies when it comes into contact with toxins produced by gram-negative bacteria, a group of pathogens that account for 70–80% of all sepsis cases in humans. Sepsis is a condition that occurs when the immune system has an extreme response to an infection. Without quick treatment, sepsis can rapidly lead to tissue damage, organ failure, and death.

Since the 1970s, the horseshoe crab’s quick-reacting coagulation chemistry has been used to produce LAL tests for the biomedical industry. These tests ensure the sterility of all manufactured medical equipment, surgical implants, and vaccines. If no gel forms upon contact, the sample is considered to be uncontaminated. For sepsis patients, having the ability to rapidly recognize gram-negative bacteria in the blood and receive timely interventions could significantly increase survival rates- which decrease by 7.6% each passing hour. Unfortunately, using LAL tests to detect bacterial toxins in human blood has been unsuccessful thus far due to the presence of substances in blood that interfere with the test’s validity.

Not a moment too soon, researchers in North Carolina have developed a promising solution that could save thousands of human and horseshoe crab lives each year. Current practices to supply the global demand for amebocyte lysate results in upwards of 600,000 horseshoe crabs harvested every year. The crabs are transported to the laboratory, bled for amebocyte extraction, and then returned to the sea. With an estimated mortality rate of 10 to 30%, this process is hardly sustainable.

Fortunately, the North Carolina team has developed an indoor recirculating aquaculture system that ensures high-quality amebocyte harvesting, maximizes horseshoe crab welfare, and maintains a 100% survival rate. Their revolutionary system consists of two holding tanks (4 ft x 5 ft x 1 ft), a biofiltration tank, and a solids separation tank. Water is supplemented with oxygen and continuously recirculated to enable routine purification, better hygiene, and disease prevention.

With this new approach, a single cohort of just 60,000 Atlantic horseshoe crabs could be sustainably bled up to 24 times each year and surpass the current LAL demand. Furthermore, the lysate extracted from horseshoe crabs raised in an aquacultural environment demonstrated enhanced levels of reactivity and the ability to detect pathogenic bacteria in human blood for the first time. This is potentially life-saving news for sepsis patients worldwide.

This new aquacultural practice has the potential to change the current way the biomedical industry operates and offers a sustainable source of abundant and reactive amebocyte lysate. Whether the biomedical field will adopt this new practice is yet to be seen. In the meantime, researchers continue their efforts to shift the field towards a more sustainable path. Hopefully, there will be enough time for scientists to step in and save the day for the animals that have long been saving our lives.

136761cookie-checkHorseshoe crabs are critical to the biotech industry A new technique in aquaculture has demonstrated a promising ability to improve survival rates, health, and performance of horseshoe crabs harvested for the biomedical industry.

Study Information

Original study: Horseshoe Crab Aquaculture as a Sustainable Endotoxin Testing Source

Study published on: April 1, 2020

Study author(s): Rachel Tinker-Kulberg, Kristen Dellinger, Terry E. Brady, Lee Robertson, Jerrold H. Levy, Sarah K. Abood, Frank M. LaDuca, Christopher L. Kepley and Anthony L. Dellinger

The study was done at: Kepley Biosystems Incorporated, United States; North Carolina A&T State University, United States; Duke University School of Medicine, United States; University of Guelph, Canada; LADUCA Regulatory, Quality, Compliance and Scientific Advisors LLC, United States; University of North Carolina at Greensboro, United States

The study was funded by: The authors acknowledge the following funding sources: National Science Foundation Small Business Innovation Research Grant program (Grant #1819562); North Carolina Board of Science and Technology; One North Carolina SBIR Matching Funds Program; and North Carolina Sea Grant (Grant #2017-R/MG-1712)

Raw data availability: All datasets generated for this study are included in the article/supplementary material.

Featured image credit: https://pixabay.com/photos/horseshoe-crab-marine-life-ocean-1869338/