Trawling for prey at more than a thousand feet under the surface, the scalloped hammerhead shark relies on a special oil in its liver to survive the crushing pressures of the deep.
Shark liver oil, or squalene, is a fatty substance that provides vital buoyancy for this critically endangered species and many others. But it’s also a lifesaver for humans as a boosting agent in vaccines, called an adjuvant, that improves the immune system and makes vaccines more effective.
As the world’s pharmaceutical companies scramble to create a vaccine for COVID-19, at least five of the 202 vaccine candidates rely on squalene sourced from wild-caught sharks. The Pfizer and Moderna coronavirus vaccines, which have both demonstrated early success, do not need adjuvants.
One candidate is a vaccine developed in Australia by University of Queensland, in partnership with the Australian biopharmaceutical company CSL and its subsidiary Seqirus. The as yet unnamed vaccine contains the squalene adjuvant MF59, which is sourced from a variety of shark species. It entered human clinical trials earlier this year and, if successful, will result in an initial production of 51 million doses.
Tens of millions of sharks are caught and traded internationally each year—both legally and illegally—the majority for their meat and fins but roughly three million or more for their squalene. It takes the livers of between 2,500 and 3,000 sharks to extract about a ton of squalene.
Conservationists fear that increased demand for squalene for vaccines, among other uses, could further imperil shark species, a third of which are vulnerable to extinction.
“This is an unsustainable demand to place on a finite natural resource like sharks,” says Stefanie Brendl, founder and executive director of Shark Allies, a California-based conservation nonprofit. (Here are the most fascinating shark discoveries of the past decade.)
Only about one percent of squalene ends up in vaccines, and most goes into cosmetics such as sunscreen, skin creams, and moisturizers. Even so, as the global population booms, the need for vaccines will only increase in coming years, Brendl notes, adding that some medical experts suggest that people will require multiple doses of vaccines against COVID-19.
“We're not saying that vaccine trials should stop, but if we keep viewing sharks as an easy solution and don’t consider the alternatives that exist, then we’ll just continue to use [squalene] as a template for vaccines,” Brendl says.
In light of declining shark populations, some biotech companies are looking for other sources of squalene. Plants such as sugarcane, olives, amaranth seeds, and rice bran, for instance, all contain the substance. While plant-based alternatives are being tested in studies and clinical trials, regulatory agencies such as the U.S. Food and Drug Administration have yet to approve them as part of a final vaccine product.
‘Livering’—a growing industry
For centuries, people have exploited shark livers for food and energy—liver oil, for example, fueled streetlights across 18th-century Europe. The oil has also long been used in textiles and food coloring, as well as cosmetic products.
But it wasn’t until 1997 that Chiron—a former biotech company that’s since been acquired by Novartis—used squalene as an adjuvant in the FLUAD influenza vaccine. Other major pharmaceutical companies, such as GSK and Novartis, began to rely on squalene for their seasonal flu and swine flu vaccines.
While the overwhelming majority of sharks are unintentionally caught by large-scale fisheries pursuing tuna, squid, and salmon, deficiencies in reporting mean it is difficult to disentangle legitimate bycatch from illegal fishing activities. The species of shark being traded is also rarely identified in trade records.
To meet the demand for shark livers, a specialized industry of fishermen, producers, and traders have developed, especially in Indonesia and India. In a process dubbed “livering,” fishermen kill a shark to remove its liver, then throw the rest of the carcass overboard.
In processing centers on land, the livers are minced, boiled, and placed in tanks, where they’re put in a centrifuge to separate the oil from any residue. The oil is then packaged and shipped around the world. One ton of shark liver oil could be worth thousands of dollars, depending on its squalene content. (Learn more about why sharks are overfished for their fins.)
In a 2014 report, the nonprofit WildLifeRisk described a factory in southeastern China that was illegally processing 600 whale sharks—a protected species—and basking sharks a year.
‘Natural white blood cells’
Though all sharks have squalene, fishermen target deep-sea species, which have the biggest livers and thus the highest concentrations of the oil. These sharks are especially vulnerable to overfishing because they mature slowly—some take a decade to begin reproducing.
As a result, nearly half the 60 shark species most wanted for their livers—including the scalloped hammerhead, the longfin mako, and the whale shark—are considered vulnerable to extinction by the International Union for Conservation of Nature (IUCN), the body that sets the conservation status of wild animals and plants.
Many of those species are protected under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), which restricts or bans fishing of certain marine species such as sharks and rays.
Joanne Cleary, a spokesperson for Seqirus, which uses the squalene adjuvant MF59, told National Geographic that their squalene is sourced from shark species that aren’t protected under CITES. In a follow-up request, Cleary did not say whether Seqirus' suppliers meet sustainable fishing standards set by the Marine Stewardship Council. (Read how reef sharks are in major decline worldwide.)
According to Brendl, of Shark Allies, “just because a fishery avoids protected species doesn’t mean it’s sustainable. Only a handful of species are legally protected, and getting a new one onto protection lists takes years.”
Losing top marine predators, such as the scalloped hammerhead, could be disastrous for the environment, says Austin Gallagher, a National Geographic Explorer and chief scientist at Beneath the Waves, a Virginia-based shark-conservation group.
“Sharks play a crucial role as the natural white blood cells of our oceans,” Gallagher says. “They keep our ecosystems robust by eating other animals that are sick, injured, or not fit to pass on their genes. They're agents of natural selection in the most poetic way.” (Explore the world of sharks, lords of the sea.)
Purity in question?
Brendl says the onus is on pharmaceutical companies to begin developing viable alternatives to shark squalene to present to regulators. She points out that Novavax, an American vaccine-development company, is already using an alternative squalene adjuvant, Matrix-M, in clinical trials for its experimental COVID-19 vaccine. Matrix-M is made from the bark of the soapbark tree, which is abundant in Chile.
Though the company has deemed the soapbark adjuvant as safe, it has not yet been evaluated as part of a final product submitted to the U.S. Food and Drug Administration.
Cleary, the Seqirus spokesperson, says that “at this stage, [alternative] squalenes have not been approved by regulators for use in vaccines due to the purity levels required.”
However, the Infectious Disease Research Institute found that pharmaceutical-grade squalene produced by the American biotechnology company Amyris met, and in some cases exceeded, the safety and purity profiles of shark-based squalene, according to Chris Paddon, Amyris’s lead scientist.
Amyris is banking on sugarcane as a solution to shark-based squalene, he says. In southeastern Brazil, the company is growing thousands of acres of the bamboo-like sugarcane to be processed into squalene. Just 24 acres of sugarcane could, in theory, produce enough squalene to support one billion COVID-19 vaccines, (Read why vaccines are so crucial to human health.)
Because growers can control the way sugarcane is grown and harvested, it’s possible to ensure the quality of the squalene, Paddon says. “When you use animal products, there are impurities that come with them because of the environment they’re raised in and the places where they’re processed.” Furthermore, Paddon says, growing sugarcane is also cheaper than catching sharks and removing their livers.
Beneath the Waves' Gallagher adds the pandemic has heightened public scrutiny of the vaccine-development process and exactly what goes into our medicines.
"One of the other significant things that also has come out of this pandemic,” he says, “has been simply shining a light on the greater environmental issue at hand here, which is the significant loss of sharks from our oceans that is happening at a global scale.”