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‘Blue-blood’ horseshoe crabs suffer from commercial bloodletting. One Penn student says he has an answer

When Aravind Krishnan was 14, he visited the Jersey Shore with his family. But it wasn’t swimming in the ocean or eating cotton candy on the boardwalk that caught the teen’s attention.

A conversation with a park ranger about prehistoric horseshoe crabs lining the beach had the greatest impact on Krishnan during the visit. He was shocked to learn that every year, up to 1 million of the species are collected, taken to a lab, stabbed with a needle and bled for biomedical purposes.

Valued at $60,000 per gallon, horseshoe crabs’ bright blue blood responds to bacterial toxins by clotting, which helps determine the virility of vaccines and medical devices. Though the crabs are returned to the ocean, an estimated 15 to 30 percent die from the bloodletting.

Following the beach trip, Krishnan began a quest to save horseshoe crabs and the ecosystem dependent upon their yearly migration to the beaches of the mid-Atlantic, where they mate at midnight during a full and new moon.

Krishnan was determined to find an alternative, and his research led him to the Arabidopsis thaliana plant, which like horseshoe crab blood, responds to bacterial toxins. Now a junior at the University of Pennsylvania, Krishnan is developing a technology — ToxiSense —- which allows the plant to produce light at different intensities based on how much bacterial toxin is in a sample.

“No longer do we need to damage coastal ecosystems and harvest these horseshoe crabs. We can just grow genetically engineered plants and use the engineered cells from these plants to test for these bacterial toxins,” the 21-year-old said.

In an effort to protect the “living fossils,” and the greater ecosystem, environmentalists have long advocated for an end to the practice of taking horseshoe crab blood. The crabs’ eggs are a food source for endangered red knot birds, which make a stop on the U.S. coast during their 9,000-mile migration from South America to the Arctic.

“While it is not an animal that many of us think of, almost all organisms in the coastal ecosystem ultimately depend on these crabs,” said Krishnan, who developed his love for the environment as a young Boy Scout.

Horseshoe crabs have existed for more than 400 million years, surviving several mass extinction events. However, their populations drastically reduced in the 1990s, partly because they were overharvested and used as bait for eels and whelk.

The U.S. Fish & Wildlife Service reports that red knots declined about 75% from the 1980s to the 2000s, largely because of reduced horseshoe crab eggs. Though harvesting restrictions have improved horseshoe crab populations, red knot numbers remain critically low, according to some surveys.

New Jersey has a moratorium on the commercial harvesting of horseshoe crabs, but provides exemptions for blood collection. While Delaware has a permitting process for both, biomedical collection does not currently exist in the state.

Last year, the pharmaceutical regulatory authority, U.S. Pharmacopeia, announced a proposal to simplify the use of synthetic alternatives to horseshoe crab blood. Although a synthetic alternative was developed decades ago, drug companies have faced regulatory hurdles when trying to use it.

Krishnan said these synthetic alternatives have some drawbacks, including the range of bacteria they can detect. He said he believes his technology would perform better and also have fewer manufacturing costs.

Plant-based solution is more sustainable and more affordable

As a high school student, Krishnan contacted about 100 university professors in a search for a mentor. Almost all never responded. But Rutgers University professor of plant biology Eric Lam took a chance on Krishnan, welcoming him to his lab every evening after school.

After enrolling at the University of Pennsylvania, Krishnan’s idea helped him and some fellow students win the Venture Lab Startup Challenge pitch competition.

“We were all very impressed and surprised, and so were our judges,” said Trang Pham, executive director of Venture Lab. “I think what is so amazing about this project is that it’s like a moonshot idea. The second part of it is that … there was a lot of real evidence that this one student was very, very serious about it. He’s essentially dedicated his life’s work to this.”

Krishnan is now enrolled in a dual degree program that allows him to major in molecular biology while studying business at the Wharton School. He also received the University City Science Center’s Founders Fellowship, which provides resources for life science entrepreneurs.

Krishnan said not only does he believe his technology is effective, but at less than $1 per test is also more affordable than a $60,000 gallon of horseshoe crab blood.

“While this method has been in use for about four decades now, there’s two big disadvantages,” Krishnan said. “One is that it’s extremely unsustainable. There have been huge ecosystemic impacts not only for horseshoe crabs, but for coastal ecosystems worldwide. And secondly, the cost.”

Jeffrey Babin, the engineering faculty director of Venture Lab, has mentored Krishnan over the past few years.

“It’s the type of thing that we love to see our students work on — something that they’re personally committed to, and that they feel can make a difference, a difference in the world, a difference in business, a difference in the environment. And it’s got all the right ingredients,” he said.

Krishnan, who fell in love with genetic engineering in the 4th grade, hopes to pursue a doctorate and eventually take his idea to market. However, there are a number of hurdles along the way. He must pilot the technology before applying for regulatory approval, which can take several years. Venture Lab’s Trang Pham said Krishnan’s biggest task will be raising the millions of dollars required for this endeavor.

Krishnan said he hopes his story will inspire other citizen scientists and young people, as well as encourage mentorship for youth.

“There’s numerous problems that we see in our society today and numerous inequities we see and we often feel powerless to address them,” he said. “But I think that this journey shows that just by beginning with small steps, those small steps can snowball into large effects and large movements.

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Kristen Fitch

Senior Director, Marketing