The Horseshoe Crab

The four species of horseshoe crabs are an ancient (~450 million years old) and important species that support the ecological function of estuaries and the survival of migratory shorebirds. The current over-exploitation of horseshoe crabs is sadly not dissimilar to other mismanaged species that were driven to extinction.

The Problem

The Harvesting of Horseshoe Crabs for the Pharmaceutical Industry

Horseshoe crabs have been integral to the safe production of injectable vaccines, drugs, and certain medical devices. In the United States, hundreds of thousands of the American horseshoe crab (Limulus polyphemus) are captured and bled alive every year for this purpose. Compounds in horseshoe crab blood effectively and efficiently detect bacterial contamination; the reaction between these compounds and contaminants is the basis of the biomedical test, Limulus Amebocyte Lysate (LAL).

LAL became the industry standard for detecting bacterial contaminants, known as endotoxins, in the late 1970s. LAL replaced the pyrogen test, which used rabbits for detecting bacterial contamination. Every injectable medication approved by the U.S. Food & Drug Administration must be tested for the potential contamination by bacterial endotoxins. Because to population growth and innovations in the pharmaceutical field, global demand for this testing process is growing.

A synthetic alternative – recombinant factor C (rFC) – was developed approximately 15 years ago by two scientists at the Nation University of Singapore, Ling Ding Jeak and Bow Ho. But the test has not achieved sufficient market penetration to decrease the industry’s reliance on the LAL by any significant amount. Revive & Restore seeks to find and remove barriers to the adoption of this synthetic alternative in order to stop the bleeding of horseshoe crabs – a procedure which kills between 15 and 30 percent of bled crabs and poses unknown long-term risks to the species.

The biomedical applications of horseshoe crab blood create a huge demand for the horseshoe crab; about half a million are bled annually in North America. But the pharmaceutical industry alone isn’t responsible for the over harvest of this species. Not only are the crabs captured and bled for biomedical applications, about 500,000 are also harvested as bait for the eel and conch fisheries.Compounding the threat of over harvesting are the effects of climate change; more intense storms and rising sea levels are diminishing the availability of suitable spawning habitat for the horseshoe crab.

The situation is more dire in Asia; in addition to the huge take of crabs for biomedical testing, food, and other uses – massive shoreline alterations on the continent are destroying estuary habitats for horseshoe crabs and migratory shorebirds at an unprecedented scale. All three Asian horseshoe crab species have been modeled to go functionally extinct in seven years under current harvest rates.

All of these issues warrant concern and immediate conservation action solely to protect this ancient animal. But the bleeding and over-harvest of the horseshoe crab is causing significant ecosystem-level impacts as well. Most notably, along the Atlantic Flyway of North America, six species of long-distance migrant shorebirds synchronize their northward migration to gorge on the eggs of spawning horseshoe crabs on their way to Arctic nesting grounds. A recent study has confirmed the highly-correlated relationship between the availability of horseshoe crab eggs and the survival of long distance migratory shorebirds. Whether a similar relationship exists between migratory shorebirds in the Asian Far Eastern flyway and horseshoe crabs is not known.

Learn more about the synthetic substitute to Horseshoe Crab blood here.

The Red Knot (Calidris canutus) depends upon Horseshoe Crab eggs for the last leg of its extraordinary spring migration from the tip of South America to the Canadian Arctic. As the numbers of horseshoe crabs decline, so too does the red knot population. The bleeding and over-fishing for the crabs continues despite the fact that horseshoe crab numbers in Delaware Bay appear to be at only a third of historic numbers. The eggs and larvae of the horseshoe crab also form an important food chain link that should be supporting Delaware Bay’s sport fishery. For any meaningful recovery of this bird, horseshoe crabs must return to spawn on the beaches of Delaware Bay in greater in numbers.

The Solution

Creating an Incentive for the Adoption of a Synthetic Substitute

Recombinant Factor C (rFC) – a synthetic substitute for LAL – was developed by Dr. Ling Ding and Dr. Bow Ho of the National University of Singapore in 1997.

Until recently the manufacturing and patents for rFC were licensed to Lonza – one of four LAL manufacturers in the United States and one of three rFC manufacturers in the world. With the expiration of patent protection in the U.S., there is now an economic incentive for additional suppliers to begin producing rFC. In turn, the addition of new rFC manufacturers will end an important barrier to adoption for the pharmaceutical industry, which has been hesitant to transition to the synthetic alternative without a robust number of suppliers.

Lingering doubt on the efficacy of rFC has also been an important barrier to adoption of rFC. Although there is now abundant evidence that the efficacy of the synthetic alternative is equivalent to or better than LAL, adoption of new technology is difficult and change has come slow to the industry. Since the development of the rFC test, numerous studies have been conducted to evaluate its efficacy and comparability to the LAL test for a wide variety of potential applications. Revive & Restore synthesized these studies to demonstrate that all available scientific evidence suggests that commercially-available rFC tests detect endotoxins with equivalent of better efficacy than the LAL test. In fact, rFC signals fewer false positives, which can be costly when they occur in the manufacturing process.

Revive & Restore’s efficacy review was published on May 10, 2018. We are optimistic that this will lead the pharmaceutical industry to live up to industry sustainability tenets and make the switch away from the unnecessary use of animals in the production of injectable medications.