The fishy business of shark squalene

Squalene, a fatty compound derived from the liver oil of sharks is commonly used to increase the efficacy of vaccines. But criticism is growing as activists are concerned about the use of shark liver oil in some Covid-19 jabs. Is it time to step up the search for alternatives? Darcy Jimenez finds out.

Squalene, a fatty compound derived from the liver oil of sharks, is commonly used in cosmetics due to its moisturising properties. It also serves another, lesser-known purpose: increasing the efficacy of vaccines.

Shark squalene is used as a component in some adjuvants – additives that boosts the body’s immune response to an active ingredient – in certain jabs, including a number of those being developed and produced for protection against Covid-19. 

At least five of the more than 300 coronavirus vaccine candidates currently in development make use of squalene from wild-caught sharks.

The murky waters of squalene harvesting

While only around 1% of squalene is currently used in vaccines, conservation non-profit Shark Allies’ founder Stefanie Brendl says harvesting sharks for this purpose has serious ecological consequences – and that the unprecedented demands of the pandemic could worsen the situation.

“We’re losing sharks left and right,” she says. “And the consequences of using sharks, even if you don’t care about them particularly, is that they’re an incredibly critical part of ocean health. Even though the vaccine industry says, ‘we’re using the least amount, the cosmetics industry uses a lot more’, well, we’re needing more and more vaccines.”

Brendl points to the predictions by multiple health experts that yearly Covid-19 booster shots will be necessary to keep the virus at bay.

Though it’s difficult to gauge just how many sharks are killed specifically for squalene, the UN’s Food and Agriculture Organization has estimated that it takes between 2,500 and 3,000 sharks to extract roughly a tonne of the product.

Much of the world’s shark liver oil is obtained from those caught unintentionally as bycatch, but Brendl says that the value of squalene incentivises the capture of sharks that would otherwise be freed.

The simplest message is that any ingredient taken from a wild animal is not sustainable long-term.

The lack of traceability in the squalene trade means it’s near impossible to establish how many sharks have been caught solely for squalene, let alone for use in vaccines. Either way, Brendl says, shark squalene is a finite resource, and companies will eventually be forced to move to more sustainable methods.

“Whatever is in their product has to be supplied, and if that is coming from a wild animal, it’s a problem,” she says. “Really, the simplest message is that any ingredient taken from a wild animal is not sustainable long-term, because it’s a limited resource that doesn’t replenish quickly enough.”

Wildlife protection group TRAFFIC said in a recent statement that “until there are clear, traceable products of shark liver oil from sustainable and legal sources, renewable alternatives from the agriculture sector should be used as much as possible” in vaccines.

An alternative approach

While sharks are a cheap and plentiful source of squalene – squalene makes up more than 80% of the liver oil in some species – they are not the only organism that produces the compound. Olives, yeast, bacteria and algae are just some of the alternatives from which squalene can be extracted.

In response to the ecological threat posed by the squalene market, sustainable ingredient manufacturer Amyris is investing in a plant-based alternative to shark-derived adjuvants. The California-based biotech programmes yeast or other microbes to create cosmetic and pharmaceutical ingredients, including squalene, from fermented sugarcane.

“It’s been known for a long time that sharks are under ecological pressure,” says Amyris lead scientist Chris Paddon. “And we realised that we had the technology to develop production of squalene from some of the other molecules that we were making; it seemed like something that we could do, and it seemed like the right thing to do.

“[Squalene] really stands out as one of the few western medical products that comes directly from animals, and we figured it was time to bring that into the 21st century.”

When it comes to purity and efficacy, Paddon says preclinical research has shown Amyris’s sugarcane-derived product is identical to shark squalene. A study published in Nature also found that there was no difference in efficacy between vaccines using shark-based and yeast-derived adjuvants.

[Squalene] really stands out as one of the few western medical products that comes directly from animals.

Though Amyris’s work proves that equally effective alternatives to shark squalene are available, pharma companies will need convincing if they are to adopt ingredients that can be more costly and time-consuming to produce. For Brendl, choosing renewable, plant-based adjuvants over a limited supply of shark oil isn’t just the ethical choice – it makes sense for business.

“It’s clear that shark oil will not always be available,” she says. “Banking a critical product that you have to produce by the billions on something that you might not be able to get, I think is a little bit sketchy.

“If the only switch is that you have to do a little bit of research and testing, but then in the long run you have something that you possibly could even make yourself … why wouldn’t you make the switch before you run out? With shark populations going where they’re going, as quickly as they’re going, shark oil will become rare.”

Ethical and environmental considerations aren’t the only reasons Amyris’s product is appealing to drugmakers, the company’s director of strategic operations Corbin Johnson says.

“The scalability is going to be a very big driver here,” he explains. “We’ve had interest from government agencies who are interested in deploying better pandemic responses in the future.

“Instead of having to harvest sharks as the raw material for an adjuvant, there’s already abundant supply of sugar in a variety of geographies globally – that’s not going to be a raw material that’s as prone to as much fluctuation or issues in the future.

“And in a matter of weeks, we can ferment that sugar into what will be the final product, and supply that to the industry as needed.”

A shark oil-free future?

Drugs giant GlaxoSmithKline (GSK) is just one pharma company using shark squalene-based adjuvants in its vaccine products. 

A spokesperson for GSK said the company is “actively exploring the potential for alternative sources of its raw materials when possible”, but that an alternative to shark squalene would not be available for use in their vaccines within the timeframe of the Covid-19 pandemic.

While pharma can be slow to implement change, Johnson says, Amyris is optimistic that the industry will move towards sustainable, shark-free options in the coming years.

“Every other space that we’re in has been moving all of their supply to more renewable, more sustainable alternatives he says. “When there are the added benefits of cost and performance on top of that, it just makes it the obvious choice.

“The industry as a whole has, over the last several decades, started moving away from animal-derived products,”, and that’s great. We’re now offering the technology to help expand that horizon.”

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