Marine scientists document LAL industry’s conservation of the horseshoe crab
The past year was highly eventful for the horseshoe crab (HSC) and their stakeholders. The Atlantic States Marine Fisheries Commission (ASMFC) completed a comprehensive two-year study on the status of the American HSC and found that its population was either stable or flourishing throughout the Atlantic coastal waters, and that the Limulus amebocyte lysate (LAL) industry had no negative impact on HSC or migratory bird sustainability.1 LAL is a vital protein coagulation system found in horseshoe crab blood that is capable of detecting harmful endotoxins found on the outer membrane of Gram-negative bacteria.
Last year, the Delaware Bay spawning survey observed the highest number of spawning crabs since 1998.2 At the same time, LAL firms continue to build their inventory to meet growing demands and have been debating the merits of synthetic LAL as a reliable alternative to traditional methods.
The ASMFC is the agency responsible for monitoring the status of marine fisheries in Atlantic coastal waters. This agency conducts a stock assessment every five years for each fishery to determine their wellbeing and need for management actions, and as such are an authority on the health of the HSC.
Given all of this positive data, why do activist groups such as the Audubon Society, Horseshoe Crab Recovery Coalition and Revive and Restore sadly continue to flood social media with misinformation that LAL production is harmful to the HSC and migratory birds, particularly the red knot? Their unjustified concern is that less spawning HSC females will reduce the number of eggs available for migratory birds. They assert that LAL processes kill large numbers of HSC and reduce the spawning activity of females.
Nothing could be further from the truth.
The 2019 HSC Stock Assessment1 found no evidence of excessive LAL-related mortality or long-term effects. The Assessment presented tagging data indicating that HSC bled, tagged and released did not experience a reduction in long-term survival due to bleeding when compared to HSC that were just caught, tagged and released. Marine scientists report an abundance of HSC eggs for red knots in Delaware Bay.
Threats to HSC do exist: 750,000 crabs are used as bait for commercial eel and whelk fisheries and no alternative bait has materialized. Tachypleus tridentatus, the Asian HSC used to produce TAL, was listed as endangered because there is no requirement to return them to sea after TAL processing. The value of LAL to healthcare has been a strong argument against use of HSC for bait; Limulus might face a similar fate in the absence of LAL production.
The 2019 HSC Stock Assessment represents the most recent and best information on the status of the coast-wide HSC stock. It determined that the annual mortality was 24% due to death by natural causes (age, beach stranding during spawning, predators and disease), commercial harvesting and bycatch. The Assessment focused on the Delaware Bay which contains the largest number of crabs, an estimated 30 million adults plus countless more juveniles.
Using their models for estimating abundance and mortality, one can estimate that, under the most extreme scenario, LAL processing would cost less than 0.2% of spawning HSCs in the Delaware Bay. After comparing the miniscule LAL loss with 24% total mortality and large bait harvest, the Commission determined that the LAL industry is not negatively impacting the HSC population.
The evidence is clear.
The American LAL industry is mature and stable. I established the first commercial LAL production at Chincoteague VA in 1971. Now, five HSC facilities are located from Massachusetts to South Carolina to produce FDA-approved LAL reagent. FDA’s approval in 1987 for the use of LAL reagent as an official test for bacterial endotoxin (pyrogen) led to increased production during the 1990s to meet the growing needs of parenteral industries. A single day’s production can supply a year of vaccine development and testing. At least 80 million test units are needed annually for assuring the safety of injectables, vaccines and medical devices. The HSC blood donation is similar to human blood donation. The crabs are bled for a few minutes and returned to sea unharmed. HSCs are thriving in the Delaware Bay and southeastern coastal waters.
In sharp contrast to activists’ assertions, the LAL community has had a positive impact on horseshoe crab populations through 5 decades of consistent conservation practices. From the outset, LAL firms used a return-to-sea policy to minimize impact on HSCs; the FDA made this policy a condition for LAL licensure. Baiting with HSC in South Carolina was banned by the legislature in 1991. (Bait harvest is also barred in NJ).
In 1990 Jim Finn and Benjie Swan of Finn-Tech, a New Jersey LAL producer at that time, introduced the Delaware Bay Spawning Survey that provides critical data on HSC population and migration and heightens public awareness of HSC value to ecology and healthcare.3 Reports co-authored by Swan, Hall and Dr. Carl Shuster are found at www.delawarbayhscsurvey.org. The survey continues under the coordination of Swan.
Over 300 people volunteer their time for HSC surveys along our coast and become part of citizen science events. With the aid of LAL firms, several universities and aquaria developed aquaculture methods that grow eggs to a more mature stage for release into the environment for stock enhancement. Lastly, ASMFC and LAL scientists met in 1991 to formulate LAL Best Management Practices and agreed on best conservation measures and reporting procedures to regulators. Only healthy crabs are bled to avoid bacterial contamination of valuable LAL reagent. Conscientious watermen care for the HSC entrusted to them. Educating and informing the public on the value of the HSC and LAL production has encouraged watermen to cease needless destruction of HSCs because of inadvertent entanglement in their fishing gear.
Technical advances reduce LAL needs.
Charles River, a life sciences company and leader in LAL manufacturing, attained FDA approval and licensing for a LAL-cartridge based microfluidic technology that reduces the amount of LAL needed by 95% compared to the traditional test. Recombinant LAL products (e.g. rFC) are being evaluated for robustness, specificity and sensitivity.4 The FDA has zero tolerance for endotoxin contamination and will not approve these products until they are validated as equivalent and specific as LAL for endotoxin detection. Baxter Travenol documented LAL’s sensitivity and specificity for endotoxin by conducting 356,548 LAL tests and 66,594 rabbit tests on pharmaceutical waters. A similar study is essential for accepting alternative LAL methods. The US Pharmacopeia committed to introducing an Informational Chapter that will provide a guideline for comparing synthetic LAL products with the HSC-derived LAL using reference standards and naturally-occurring endotoxin in pharmaceutical water samples.
Without the proper research and understanding of the impact this invaluable species has on our ecosystem and everyday health, one could think moving towards the current synthetic technology to reduce our burden on HSC’s is the right move. But in actuality, the biomedical industry is the strongest advocates for this species protection and preservation. The safety of every single injectable is dependent on this animal. Until there is a safe, proven, and reliable technology that is equivalent to the remarkable blue blood of the HSC, we will continue to fight for its protection, and you should too.
1. ASMFC http://www.asmfc.org/uploads/file/5cd5d6f1HSCAssessment_PeerReviewReport_May2019pdf.
2. Swan BL, Hall W, Shuster CN Jr. The 2019 Delaware Bay Horseshoe Crab Spawning Survey. www.DelawareBayhscsurvey.org
3. Swan BL 2005 Migrations of adult horseshoe crabs, Limulus polyphemus, in the middle Atlantic bight: a 17-year tagging study. Estuaries 28:28-40.
4. Tsuchiya M 2020 https://doi.org/10.37118/ijdr.19019.05.2020.
Link here to learn more about Charles River’s efforts to conserve horseshoe crabs.