You probably never heard about the Horseshoe Crab, but most of us are alive thanks to this animal. First, don't get confused with their name because they are not crabs.Indeed they are not even crustaceans; this 10-eyed prehistoric-looking animal is more related to spiders (1,2). Recent fossil discoveries show that the earliest accepted horseshoe crabs lived some 445 million years ago (3). Their perfect design hasn't required any evolution ever since.They are not strong or fast, but they have outlived the dinosaurs, perhaps is the fact that a female can lay up to 120,000 eggs in a single season! (4) (Figure 1).
But there is something about these strange creatures that make them invaluable for human beings:Their blue blood (Figure 3). A single liter is worth around $15,000 (5). Their hemolymph (as the blood of arthropods is referred to) carry the key ingredient of the Amebocyte Lysate, the global standard test for screening medical equipment for bacterial contamination (6,7). In short, horseshoe crab blood helps to detect toxins in any injectables for vaccines, medications, and even internal prostheses, ultimately preventing unexpected toxins from entering our body during medical treatments.
There are four extant Horseshoe crab species; three are located in Asia, and one in America. All four species are used for the same purpose, among others. However, the procedures are different in the east from the west.
"In theUnited States, an estimated 440,000 specimens are collected each year to extract their blood", declares Dr. Mark L. Botton, Professor of Biology atFordham University and Co-chair of the IUCN Horseshoe Crab Specialist Group.
The process starts with the capture of the animal. Wild horseshoe crabs are collected from the bottom of the shallow waters with dragging trawls. The animals are transported to the biomedical facility in dry containers, where they often suffer overcrowding and dehydration. Once in the facility, a hypodermic needle is placed directly into the exposed pericardial membrane, and up to 40% of their hemolymph is taken from their body. Once the procedure is done, the exhausted, traumatized and sometimes dying horseshoe crabs are returned to their habitat (8,9).
Dr. Botton says that, in any case, the exploitation of horseshoe crabs in the USA is more sustainable than in Asia."There are fishery management practices in place that are aimed at keeping the population sustainable for the migratory birds that feed on the crab eggs, whereas in Asia, the regulations are not as strict, and enforcement might be questionable," declares the Professor. According to Dr. Botton, the mortality under correct management circumstances is less than 15%."Studies show that after being released, there is some stress for a couple of weeks, after which they seem to recover fully," states Dr. Botton.
In contrast, the second country with more catches is China, where bleeding operations are not sustainable. The practice is to drain all of the animal's blood resulting in its death (10). In China, 200,000 specimens are milked a year. However, there is alack of transparency in the shared data, making this number somewhat unrealistic and impossible to verify. In this region, unrestricted capture to supply blood to the biomedical industry has been recognized as a major contributing factor to their significant population decline (11).
Of course, the main threat to horseshoe crabs is not the pharmaceutical industry. Even more worrying is the loss of habitat, overfishing, and pollution in the sea, causing the four species to be threatened (12).
In China, humans are demanding this species as a culinary treasure (Figure 4) (11). A threat that reaches beyond China and animals are extracted from other countries such as Vietnam and Cambodia. Considering the region has the highest rate of habitat loss on the planet13, there is no surprise the populations of all three Asian species are declining (12).
The near-term threat to Horseshoe Crabs in America is unsustainable harvesting (14). "The use as bait for fishing in the United States is a far greater threat for horseshoe crabs and implies a mortality ten times greaterthan the biomedical industry," declares Dr. Botton. In 2012 alone, morethan 700,000 animals were reported for bait in the USA (Figure 5) (15).
The long-term and emerging threat toHorseshoe Crabs is habitat loss due to climate change and land use. Habitat conditions could change as coastlines are developed and impacted by climate change (14).
Horseshoe crabs are not only important to humans; they also play an essential role in their ecosystem, being an important source of food for migratory birds and sea turtles, among other animals (16,17). Six species of shorebirds synchronize their northward migration along the Atlantic flyway to feast on the eggs of spawning horseshoe crabs, a critical food stop on their journey to Arctic nesting grounds (Figure 6) (18).
This is the big question that causes massive conservation concern: We just don't know.
Most endotoxin detection is performed using Amebocyte Lysate for vaccines, other medicines, and surgical gear19. However, in a year in which the production of vaccines and medicines has increased exponentially, the industry has not yet provided data on the impact produced in horseshoe crabs. Furthermore, fewer field data is available, and fewer conservation actions are being made in the year of lockdown, travel restrictions, and economic plunge.
Dr. Botton declares that there is significant concern on the direct and indirect causes of the COVID19 vaccine development over the horseshoe crabs. Still, within the pharmaceutical industry, they ensure that supplies will be sufficient for the vaccine's needs.At the same time, little attention is placed on the future of the species responsible for the safety of that very same product.
"Any further stress on an endangered species is always a great concern." Declares Dr. Botton.
Recently and only in Europe, a synthetic alternative as effective as Amebocyte Lysate has been approved18. However, after 50 years of Amebocyte Lysate use, laboratories will take time to transition to the new product. Let's hope it's not too late for our lifesaver horseshoe crabs.
Think about it if you get vaccinated, you can do it thanks to them.
We would like to thank and acknowledge Dr. Mark Botton for the valuable information provided for the development of this article (Figure 8). Dr. Bottom has been studying horseshoe crabs since the 1970s. Dr. Botton even had a horseshoe crab fossil named after him (Albalimulus bottoni). He is in charge of analyzing and reporting threat levels in horseshoe crabs for the International Union for The Conservation of Nature.
1. Ballesteros,J. A. & Sharma, P. P. A Critical Appraisal of the Placement of Xiphosura(Chelicerata) with Account of Known Sources of Phylogenetic Error. Syst.Biol. 68, 896–917 (2019).
2. Garwood, R. J. & Dunlop, J.Three-dimensional reconstruction and the phylogeny of extinct chelicerate orders.PeerJ 2, e641 (2014).
3. Rudkin, D. M. & Young, G. A.Horseshoe Crabs – An Ancient Ancestry Revealed. in Biology and Conservationof Horseshoe Crabs (eds. Tanacredi, J. T., Botton, M. L. & Smith, D.)25–44 (Springer US, 2009). doi:10.1007/978-0-387-89959-6_2.
4. Tanacredi, J. The Coastal MonitorWinter/Spring 2020. (2020).
5. Dolejš, P. & Vaňousová, K. Acollection of horseshoe crabs (Chelicerata: Xiphosura) in the National Museum,Prague (Czech Republic) and a review of their immunological importance. Arachnol.Mitteilungen 49, 1–9 (2015).
6. Levin, J. Clotting cells and Limulusamebocyte lysate: an amazing analytical tool. Am. Horseshoe Crab 310–340(2003).
7. Novitsky, T. J. Biomedical applicationsof Limulus amebocyte lysate. in Biology and conservation of horseshoe crabs315–329 (Springer, 2009).
8. Anderson, R. L., Watson III, W. H.& Chabot, C. C. Sublethal behavioral and physiological effects of thebiomedical bleeding process on the American horseshoe crab, Limulus polyphemus.Biol. Bull. 225, 137–151 (2013).
9. Krisfalusi-Gannon, J. et al. TheRole of Horseshoe Crabs in the Biomedical Industry and Recent Trends ImpactingSpecies Sustainability. Front. Mar. Sci. 5, 185 (2018).
10. Hong, S. Biology of horseshoe crabs,Tachypleus tridentatus: Xiamen, China. (Xiamen University Press, 2011).
11. IUCN. Tachypleus tridentatus: Laurie, K.,Chen, C.-P., Cheung, S.G., Do, V., Hsieh, H., John, A., Mohamad, F., Seino, S.,Nishida, S., Shin, P. & Yang, M.: The IUCN Red List of Threatened Species2019: e.T21309A149768986. (2018)doi:10.2305/IUCN.UK.2019-1.RLTS.T21309A149768986.en.
12. IUCN. IUCN 2020. The IUCN Red List ofThreatened Species. Version 2020-3. <https://www.iucnredlist.org> ISSN2307-8235. (2020).
13. Chao, N., Duckworth, J. W. & Rao, M.Asian Species Action Partnership: Strategy 2018-2023. IUCN SSC Asian SpeciesAction Partnership.https://www.speciesonthebrink.org/wp-content/uploads/2019/04/ASAP-Strategy-2018-2023.pdf.(2019).
14. IUCN. Limulus polyphemus: Smith, D.R.,Beekey, M.A., Brockmann, H.J., King, T.L., Millard, M.J. & Zaldívar-Rae,J.A.: The IUCN Red List of Threatened Species 2016: e.T11987A80159830. (2016)doi:10.2305/IUCN.UK.2016-1.RLTS.T11987A80159830.en.
15. Eyler, S. 2015 review of the Atlanticstates marine fisheries commission fishery management plan for horseshoe crab.(2014).
16. Botton, M. L. The ecological importanceof horseshoe crabs in estuarine and coastal communities: a review andspeculative summary. in Biology and conservation of horseshoe crabs45–63 (Springer, 2009).
17. Haramis, M. G. et al. Stable isotope and pen feeding trialstudies confirm the value of horseshoe crab Limulus polyphemus eggs to springmigrant shorebirds in Delaware Bay. J. Avian Biol. 38, 367–376(2007).
18. Maloney, T., Phelan, R. & Simmons, N.Saving the horseshoe crab: A synthetic alternative to horseshoe crab blood forendotoxin detection. PLOS Biol. 16, e2006607 (2018).
19. Gauvry, G. Current horseshoe crabharvesting practices cannot support global demand for TAL/LAL: thepharmaceutical and medical device industries' role in the sustainability ofhorseshoe crabs. in Changing global perspectives on horseshoe crab biology,conservation and management 475–482 (Springer, 2015).
*Cover photo: Horseshoe crab. Breese Greg. License under Creative Commons