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Using synthetic crab blood substitute in biomedical testing could help save horseshoe crabs and shorebirds

Using synthetic crab blood substitute in biomedical testing could help save horseshoe crabs and shorebirds
A horseshoe crab with sand is pictured on its shell during spawning season June 11 at Pickering Beach near Dover, Del. More horseshoe crabs will mean more people are needed to flip over the animals that get stuck on the sand during the annual frenzy to spawn. (Maddy Lauria / The News Journal via AP)

For the first time in decades, Glenn Gauvry is lamenting the sight of so many horseshoe crabs getting stuck in the sand along the Delaware Bay beaches.

What he's seeing in the sand hints that the crab population might be starting to recover from the days of overfishing them for fertilizer, livestock food and bait.

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That's good news for people all over the world, since nearly every person and pet on the planet has been aided by horseshoe crabs because their blood is used to make sure medical equipment is safe.

The trouble is that the number of volunteers in the "Just Flip 'em!" program Gauvry started in the mid-1990s has remained about the same.

More horseshoe crabs will mean more people are needed to flip over the animals that get stuck on the sand during the annual frenzy to spawn and help them escape back to the water.

"Once people start to connect to these animals, they'll start to help them," said Gauvry, who also serves as mayor of Little Creek and president of the Ecological Research & Development Group. "Then there are less dying on the beach and smelling and attracting flies and interfering with their ability to recreate."

Glenn Gauvry of the Ecological Research & Development Group poses with spawning crabs June 11 at Pickering BeachGauvry advocates for the conservation of horseshoe crabs.
Glenn Gauvry of the Ecological Research & Development Group poses with spawning crabs June 11 at Pickering BeachGauvry advocates for the conservation of horseshoe crabs. (Maddy Lauria / The News Journal via AP)

Once people start to connect to these animals, they'll start to help them.


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He's not the only one tracking the horseshoe crab population, which plays a key part in long-range shorebird migration every year.

A story recently published by The New York Times suggested the birds that rely on horseshoe crab eggs for surviving long flights are starving during their stopovers in the Delaware Bay because there aren't enough eggs to eat.

At the same time, the most recent data from a federal commission that studies horseshoe crabs along the eastern Atlantic shows stability in numbers and even an increase in some East Coast regions.

A decade from now, there could be more gains in the population if the biomedical industry embraces a synthetic substitute for the ancient creatures' unique blue blood.

That blood contains a component that for more than half a century has been making sure injectable or implantable medical products — such as needles and intravenous medications — do not contain specific agents that can cause fevers or even death.

It's been about 15 years since a synthetic replacement first was developed for the component in horseshoe crab blood that detects those harmful toxins embedded in the walls of bacteria.

But because the synthetic chemical costs are about the same as using fresh blood itself, companies like Indiana's Eli Lilly and Co. now only have the incentive of changing to show they are sustainable or environmentally friendly.

For many, that may be well worth the startup cost that comes with testing a newer product, said Eli Lilly senior consultant biologist Jay Bolden.

"It's beneficial to us, it's beneficial to the horseshoe crabs, it's beneficial to the shorebirds," he said. "People need to know there is an alternative."

"In our opinion, it's the right thing to do," said Allen Burgenson of the pharma/biotech company Lonza, which created a synthetic product.

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But, like all moneymaking businesses, it might take more than good will to see that switch go industry-wide, he said.

"Unless it hits the bottom line, they really aren't going to use an alternate technology unless it makes the result cheaper or come in faster or work better with their products," he said.

On a warm Tuesday morning in early June, Gauvry stood at the entrance to Pickering Beach as about two dozen professionals from the pharmaceutical and biomedical fields filed off a tour bus.

It's the fifth year Lonza employees have trudged through the sand and pebbles to see the annual gathering of horseshoe crabs. The prehistoric species is one some of them have only known through the blue blood used in Lonza's laboratories.

For Tammy Thurman, a senior scientist with Pfizer, visits to Pickering Beach have inspired her to look at the endotoxin testing made possible by crab blood in a bit of a different way.

Scientists like Thurman and those from Lonza use horseshoe crab blood to test for the presence of potentially lethal endotoxins. Those substances found on bacteria can cause fevers, organ failure and even death.

In the early days of modern medicine, endotoxin poisoning was called "injection fever," a known risk during dangerous procedures.

Later, medical devices like needles would be tested first on rabbits to see whether they developed a fatal fever before the products would be used on humans. By the 1970s, scientists discovered the fantastic clotting properties of horseshoe crabs' copper-based blood.

Now scientists have figured out how to re-create the life-saving properties found in horseshoe crab blood to make a synthetic product called recombinant factor C.

"I feel we should make the switch," Thurman said. "But this is going to take time. It seems better in theory, but you have to have the data."

She said she expects the industry will eventually embrace synthetic blood, but can't predict when that might happen.

"That's the million-dollar question," she said. "We just have to prove it works and then data will drive it."

In the meantime, she and others at Pfizer are testing the synthetic product on water samples first. They'll see how those tests turn out and take it from there.

Lonza and Eli Lilly have already done the heavy lifting to compare the product to the known success of horseshoe crab-based LAL testing (LAL stands for limulus amebocyte lysate and the LAL test is used to detect the presence and amount of endotoxins in a medical product).

Lonza has been trying to market its synthetic product for about 15 years. Now, Eli Lilly has vowed that any new product it creates will be tested with a factor C product rather than with the real blood-based test.

Away from those laboratories is a spectacle seen every year from May through July. Hundreds of thousands of horseshoe crabs amass along the shores of the Delaware Bay as the tide rolls in.

Smaller male crabs gather around the larger females, which can lay upwards of 100,000 tiny, greenish eggs in the moist sand along the tide line. In their wake, shorebirds swoop in to gobble up exposed eggs.

Previous studies have suggested this event in part contributes significantly to Delaware's multimillion-dollar coastal tourism industry by attracting birders and wildlife watchers from around the world.

For some of the shorebirds that attract those tourists, such as the federally threatened Rufa red knot, horseshoe crab eggs literally mean life or death. That's why many birding organizations advocate to completely stop the harvest of horseshoe crabs to protect a species already struggling with the impacts of climate change and habitat loss.

While observations and data from the Atlantic States Marine Fisheries Commission point to more and more horseshoe crabs surviving the perils of the Delaware Bay, the population is still not as strong as it once was.

The numbers were severely depleted from the mid-1800s through the 1920s, when up to 2 million a year were harvested for fertilizer and livestock feed.

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Another sharp decline in the wild population came in the mid-1990s, when millions of horseshoe crabs were being caught and killed each year, mainly for bait in eel and whelk fisheries. That culling, in turn, threatened the food supply for shorebirds.

Since then, New Jersey has banned the harvest of horseshoe crabs altogether. In Delaware, only a certain number of males can be caught by licensed fishers. In South Carolina, horseshoe crabs can only be caught for the biomedical industry and they must be returned after blood is taken.

The latest assessment for the Atlantic horseshoe crab population, which extends from Maine down to Florida and across the Gulf of Mexico to the Yucatan Peninsula, shows that numbers for the five East Coast regions surveyed are either stable or increasing everywhere except for New York, according to a 2019 report.

Those estimates show there are about 25 million to 30 million adult horseshoe crabs in the Delaware Bay alone.

That supports what Gauvry is seeing on the beach. He wonders whether people still want to help the populations grow, or whether interest is waning because the numbers of crabs seem to be increasing.

Switching to a synthetic product may not make a huge impact on the horseshoe crab population, Burgenson says.

Right now, only 15 percent of the crabs that are bled for biomedical purposes die, according to the highest estimate.

During that process, Burgenson said a few tablespoons of blood are taken from each crab, which is then marked and returned to the sea. The industry bleeds about 600,000, and he says the death rate is likely closer to 3 percent.

Far more horseshoe crabs — about 500,000 each year — are harvested and killed for bait.

The idea of using a synthetic product instead of real blood also carries weight not only with those who don't want to harm the crabs, but also those who fear potential losses in a disaster such as a storm or an oil spill.

Having a synthetic product ensures that biomedical companies aren't left without the product in an emergency.

"So you're not looking at another Hurricane Hugo coming in and taking out Charleston, another Superstorm Sandy taking out the Mid-Atlantic, or another hurricane taking out our competition on Cape Cod," Burgenson said.

It's not only the loss of the crabs that worries some people. The handful of laboratories that extract the blood are all located near waterways where the crabs congregate up and down the coast, but none are in Delaware. Lonza's closest is in Maryland.

With rising seas and the threat of intensifying storms exacerbated by climate change, some in the industry are concerned about what would happen to the blood supply chain if a major hurricane hit those areas and took the labs offline.

The Trump administration's support for expanding energy exploration along America's coastlines is another threat Burgenson pointed to while talking about the need for a synthetic choice.

"And where do horseshoe crabs live? In the water along the shore," Burgenson said. "Our little horseshoe crabs on the coasts are responsible for the health of the world."

Information from: The News Journal of Wilmington, Del., delawareonline.com

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