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July 21, 2022 | Tom Ballard

Those horseshoe crabs you see on the beach contribute to your personal longevity

By Tom Ballard, Chief Alliance Officer, PYA

Have you ever come across a horseshoe crab during a beach walk along the Atlantic or Gulf Coast? Chances are that you have, but never considered the fact that the species that has been around longer than the dinosaurs has most likely contributed to your longevity because of its use in developing vaccines like those for COVID-19.

There are actually four species of horseshoe crabs still in existence today. Three are found in Southeast Asia, and one – Limulus polyphemus – is found in North America along the Atlantic and Gulf coasts from Maine to Mexico. As described in this article from Ocean Conservancy, what makes them very important for medical purposes is the fact that they do not have white or red blood cells, T cells, or B cells as humans do. Instead, horseshoe crabs  only have one cell type, the amoebocyte, in their blue blood.

Researchers at Johns Hopkins University discovered in the late 1950s that an extract from amoebocytes, the limulus amoebosyte Lysate (LAL), can be used to test the safety of vaccines and other drugs.  LAL preparations rapidly coagulate in the presence of minute quantities of Gram-negative bacterial contamination.  This test is so useful that the U.S. Food and Drug Administration mandates its use for all intravenously-administered medicines.

Sounds good, you say. Glad we have horseshoe crabs.

Unfortunately, as we learned from Jennifer Watson and Richard Hatcher, Co-Founders of Nashville-based Limuless LLC, a combination of factors is contributing to the need to find an alternative to using the horseshoe crab’s distinctive bright blue blood that contains the all-important LAL.

“Harvesting for other purposes has contributed to horseshoe crabs becoming a bit more sparse,” Hatcher explains. Those reasons vary but start with the fact that only a small percentage of the eggs that mature horseshoe crabs lay actually hatch. Instead, they serve as an important source of food for wildlife like migratory birds, sea turtles and some fish species. Add that to other factors,  such as the use of horseshoe crabs as fishing bait and the fact that they cannot be raised in captivity, and there’s a real challenge on the horizon.

The husband and wife team has been working for about four years to develop a recombinant version of LAL and has filed for a provisional patent for the process as they explained earlier this year as a competitor in the annual “Venture Forum” that was part of “LSTCON,” the annual conference of Life Science Tennessee.

Their goal is to not only to provide an alternative source for something that is becoming increasingly scarce, but to also provide it at considerable savings for researchers.

“One quart of horseshoe crab blood costs $15,000,” Hatcher says. “We believe we can drop down the cost by a factor of 10. We can also make a better product.”

The couple have very different technical backgrounds. Hatcher, who serves as the start-up’s Chief Technology Officer, has an M.S. in Nuclear Engineering and worked with TVA at the Watts Bar Nuclear Plant. Watson, Chief Executive Officer and Chief Scientist, graduated cum laude from the University of Tennessee, Knoxville with a B.S. in Biomedical Engineering and a minor in Materials Science and Engineering. She later earned her PhD in Neurobiology and Neurosciences at the University of Alabama at Birmingham.

It was during time Watson spent at Dauphin Island Sea Lab that she became more aware of horseshoe crabs. “I loved the little guys and learned how valuable they are for the pharmaceuticals industry,” Watson told us.

Today, the couple has secured lab space in the Cumberland Emerging Technologies facility in Downtown Nashville as they plan for scaling the start-up that has been self-funded thus far along with some investment from friends and family.

“We’ve operated on a shoestring budget thus far,” Watson says with Hatcher adding, “It feels like things are finally taking off.” They hope to have their minimum viable product by the end of 2022. “Outside capital would clearly accelerate our development,” Hatcher says, and Watson adds, “We’re on the lookout for strategic partners.”

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