Eli Lilly and Company

11/21/2024 | News release | Archived content

Horseshoe Crabs: Protecting the Animals that Have Helped Protect Us

Horseshoe Crabs: Protecting the Animals that Have Helped Protect Us

Nov 21, 2024|
Posted by: Eli Lilly and Company
  • science
  • discovery
  • social impact
  • scientist story
  • sustainability

Horseshoe crabs look more like weird walking helmets than actual crabs. They haven't changed much in the more than 450 million years they've existed, but a lot has changed around them. (Dinosaurs came and then went!) And while that fact alone makes them unique, it's what's inside them that has been especially interesting to the medical community over the last 30-plus years.

Their blood-a milky, but vibrant shade of blue-includes Factor C. It's a protein that helps test injectable medicines for toxic contamination by naturally clotting around foreign bacteria. These contaminants-or bacterial endotoxins-can cause serious illness in humans.

Beginning in the 1970s, horseshoe crabs began playing an important role in the health and safety of medicine development. In fact, if you've taken an injectable medication or had a vaccine over that span of time, these prehistoric creatures helped make it safe for you.

Despite knowing all of this information about horseshoe crabs-and a whole lot more-it actually wasn't the crabs that initially brought Lilly Scientist Jay Bolden to the shores of Delaware Bay. It was the birds. In his spare time, Bolden counts birds for science.

"I'm a birder. That's my hobby. I've been birding for just about as long as I've been at Lilly, which was around 2000," he explains. "I keep a list, and then I upload that into a database that's used by researchers to track bird conservation."

An Ecosystem on the Verge of Crashing

So, what do birds have to do with horseshoe crabs? When Bolden began his work in the quality control lab, he realized the test he was being trained to do using lysate from the crabs-referred to as a reagent-threatened their lives.

Although the process of bleeding the crabs doesn't necessarily kill them, it weakens them, impacts their mating, and can lead to death. Between harvesting their blood to test injectable medicines-roughly 70 million tests across the pharmaceutical industry each year-and fisheries using them for bait, the horseshoe population had begun to rapidly decline. The number of harvested crabs increased from 100,000 in the early 90s to more than 2.5 million by 1998.

In turn, the population of the more than 1.5 million shorebirds-including the Red Knots, a species that's part of the federal endangered list-also declined. Like many shorebirds, the Red Knots depend on horseshoe crab eggs for fuel during their treacherous migration to the Arctic to breed.

The Red Knots are especially vulnerable to their migratory journey because they're small. By the time they reach Delaware Bay, they have flown eight straight days from the coast of Brazil and count on the eggs to build up fat for the final leg of their flight.

Delaware Bay has the largest population of horseshoe crabs in the world. During their spawning season in late spring, the crabs ride the waves ashore to clunkily navigate the rocky sand and lay eggs, their sharp-looking, mini-sword tails trailing behind them.

The peak of this clumsy ascent-which results in bumping clusters of slow-moving crabs at the water's edge-happens to be perfectly timed with the Red Knots' arrival. And it's that delicate balance-peak numbers of exposed crabs and their eggs, colliding with the birds' pit stop-that Bolden, and so many nature enthusiasts like him, are trying to restore.

"It's not all just about crabs. It's not all just about birds," Bolden explains. "It's about an ecosystem, right? You affect one piece of the ecosystem. It affects sport fish and turtles and sharks and benthic worms at the bottom of the ocean. So, to be able to understand what we do in the lab, and the impact that it has outside, that's a powerful message."

Turning the Tide: The Future with rFC

Unlike other complex environmental challenges humankind has created, this conundrum has a pretty obvious solution: recombinant Factor C (rFC). And through Bolden's passionate leadership, we're leading the industry in adopting it.

rFC is a non-animal-sourced, manufactured reagent. It provides a synthetic alternative to lysate that not only helps protect the horseshoe crabs but is also a more reliable and cost-effective option than depending on a dwindling natural resource. According to Bolden, "This was a no-brainer."

In 2016, we drew a line in the sand and began converting to rFC. In 2018, we received approval for our first official medicine using rFC testing. From there, we used it for at least eight other approvals, globally. And we don't plan to go back.

Our work to convert to rFC caught the attention of conservation scientists and organizations who invited Bolden to represent Lilly in the Horseshoe Crab Recovery Coalition and speak about the process of moving to the synthetic reagent. The group works to positively impact the environment by restoring the crab population to its early 90s numbers.

"My goal is to share our experience with our peer companies in the hopes that they will implement it," Bolden says. "Because, when we do that as an industry, and we reduce our impact on wild animals, that's going to be a net positive impact for the environment. It needs to happen."

The U.S. Pharmacopeia made a recent decision that rFC is a sustainable alternative to horseshoe crab blood, creating opportunities for it to be even more widely adopted across the industry.

Eli Lilly and Company published this content on November 21, 2024, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on September 04, 2025 at 09:03 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at [email protected]