The Value of the Horseshoe Crab in Modern Medicine

Sunday - October 22 2023, 22:45 UTC - 1 year ago

Horseshoe crabs are an important part of modern medicine. Their blood is used to produce a substance called Limulus Amebocyte Lysate (LAL) which is used to test intravenous drugs for toxins. While this is a 20th-century medical safety breakthrough, there are now criticisms of the process, primarily concerning environmental impacts and the process for reviewing and approving alternatives to horseshoe crab blood.

If you have ever gotten a vaccine or received an intravenous drug and did not come down with a potentially life-threatening fever, you can thank a horseshoe crab (Limulus Polyphemus). How can animals that are often called "living fossils", because they have barely changed over millions of years, be so important in modern medicine? Horseshoe crab blood is used to produce a substance called Limulus Amebocyte Lysate, or LAL, which scientists use to test for toxic substances called endotoxins in intravenous drugs .

These toxins, produced by bacteria, are ubiquitous in the environment and can't be removed simply through sterilization. They can cause a reaction historically referred to as "injection fever". A strong concentration can lead to shock and even death. Identifying LAL as a highly sensitive detector of endotoxins was a 20th-century medical safety breakthrough. Now, however, critics are raising questions about environmental impacts and the process for reviewing and approving synthetic alternatives to horseshoe crab blood .

We study science, technology and public policy, and recently published a white paper examining social, political and economic issues associated with using horseshoe crabs to produce LAL. We see this issue as a test case for complicated problems that cut across multiple agencies and require attention to both nature and human health. Doctors began injecting patients with various solutions in the mid-1800s, but it was not until the 1920s that biochemist Florence Seibert discovered that febrile reactions were due to contaminated water in these solutions .

She created a method for detecting and removing the substances that caused this reaction, and it became the medical standard in the 1940s. Known as the rabbit pyrogen test, it required scientists to inject intravenous drugs into rabbits, then monitor the animals. A feverish rabbit meant that a batch of drugs was contaminated. The LAL method was discovered by accident. Working with horseshoe crabs at the Marine Biological Laboratory at Woods Hole, Massachusetts, in the 1950s and '60s, pathobiologist Frederik Bang and medical researcher Jack Levin noticed that the animals' blue blood coagulated in a curious manner .

Through a series of experiments, they isolated endotoxin as the coagulant and devised a method for extracting LAL from the blood. This compound would gel or clot nearly instantaneously in the presence of fever-inducing toxins. Academic researchers, biomedical companies and the U.S. Food and Drug Administration refined LAL production and measured it against the rabbit test. By the 1990s, LAL was the FDA-approved method for testing medicines for endotoxin, largely replacing rabbits .

Producing LAL requires harvesting horseshoe crabs from oceans and beaches, draining up to 30% of their blood in a laboratory and returning the live crabs to the ocean. There's dispute about how many crabs die in the process - estimates range from a few percent to 30% or more - and about possible harmful effects on survivors. Today there are five FDA-licensed LAL producers along the U.S. East Coast .

The amount of LAL they produce, and in turn the number of crabs harvested, might have ripple effects on horseshoe crab populations and shorebirds, which feed on their eggs.