Prior to using horseshoe crabs, the pharmaceutical industry used rabbits to detect endotoxins, which led to hundreds of thousands of rabbit euthanizations every year. Every U.S. FDA approved drug must be tested for bacterial contaminants. A synthetic alternative to LAL exists, and is approved in Europe, but the U.S. Pharmacopeia, which works closely with the FDA, has not fully endorsed it (2020).
The blue blood from horseshoe crabs is the only known source of limulus amebocyte lysate (LAL). LAL is used to detect endotoxins, bacterial contaminants that can be deadly if they end up in vaccines, injectable drugs or other medical devices and implants, such as artificial knees and hips. Every year, the pharmaceutical industry captures about 500,000 horseshoe crabs on the East Coast of the U.S. and drains up to one-third of their blood. Even using conservative estimates of mortality caused by bleeding, and combining it with the 13% of bled crabs sold for bait, at least 130,000 horseshoe crabs may be killed every year by the biomedical industry. Aside from the crabs that die outright, sublethal effects, including injury and disorientation, decreased spawning and disease, are also known to occur as a result of capture, handling and transportation, and may affect horseshoe crabs for weeks following the bleeding. Population monitoring studies suggest horseshoe crab populations decreased more than 10%, or about 1% per year, from 2003 to 2014, although more striking declines have also been noted, for example near Cape Cod at Mashnee Dike, where the spawning horseshoe crab count dwindled from around 3,000 to 148: a 95.3% decline over a 15-year period (1984–1999).