Findings, music, and occasional reflections by Paul Woodward

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The rare Chilean soapbark tree that could help stop the pandemic

Brendan Borrell writes:

In early April, Paul Hiley was kicking back in the executive suite at Desert King International LLC, gazing out the window at the San Diego sunshine and daydreaming about his golf game. California had issued its initial stay-at-home order for COVID-19, but apart from the hand sanitizer around the office, life was more or less normal. Retirement was on the horizon for Hiley. Maybe he’d sell the business. Maybe his son, Damian, would take over.

For more than 42 years, Hiley has been a leading purveyor of certain plant-based food additives such as saponins, foaming agents used in root beer and Slurpees. Most of us never think about these compounds, and Hiley has always liked it that way. “My theory of business is the only two people who need to know my name are my wife and my banker,” he told me recently.

Then, one day—April 14th, to be exact—his son told him that they had a call with Stanley Erck. Erck is the CEO of Novavax, a Maryland-based maker of vaccines. Not a seller of vaccines, mind you: The company had yet to bring one of its candidates to market. But like other companies around the world, Novavax had thrown its hat into the coronavirus-vaccine race. And its success, Erck believed, depended on that odd ingredient in Slurpees.

The inner bark of the Chilean soapbark tree, Quillaja saponaria, is the source material for some of these saponins. Pulverized and soaked in water at the Desert King factory in Chile, the bark is transformed into a brown, bitter, bubbly fluid. This precious goo does many things well, and it happens to be the raw material for one of the world’s most coveted vaccine adjuvants: QS-21. Adjuvants are compounds that boost the body’s immune reaction to a vaccine. Owing to their potential risks to human health, however, only a handful of adjuvants have been approved by the U.S. Food and Drug Administration, and QS-21 is one of the newest.

A single gram of powdered QS-21 costs more than $100,000, though only about $5 worth is needed for each shot. Nine years ago, researchers estimated that the global supply of pharmaceutical-grade Quillaja extract was sufficient for just 6 million doses of vaccine. Everyone in the business knew the story of the Pacific yew tree, whose bark was the original source of the chemotherapy drug paclitaxel, and which was threatened by large-scale harvesting in the 1980s. “If you take out all the trees in one shot and deplete the source of saponin, you are in deep shit in the future,” says Garo Armen, whose company, Agenus, helped bring QS-21 to market. Novavax has its own saponin-based adjuvant, called Matrix-M, and warned investors last year that their vaccines could be delayed if they failed to “secure sufficient supplies” of high-quality extract. And the Hileys practically had a monopoly on it.

During his call with the Hileys, Erck asked if Desert King could increase their production for Novavax a hundredfold. Paul Hiley’s jaw dropped to the table. Novavax was on the cusp of receiving $384 million in international funding to help it produce 100 million doses of its COVID-19 vaccine for the world by the end of the year, and a billion doses by the end of 2021. It would also soon be on the short list of vaccine candidates funded by the Trump administration’s Operation Warp Speed. Novavax needed guarantees of 1,500 pounds of saponin now, and up to three times as much next year.

Hiley’s immediate concern was that his Chilean operation had already missed the bark-harvesting window—typically during the trees’ spring growth, between September and December. And last year he had made the ill-timed decision to postpone expanding their pharmaceutical operations in favor of investing in Desert King’s booming animal-feed business.

In the end, Hiley knew there was only one way to answer Erck: “Of course, we can deliver it,” he said. Three months later, inside the Desert King conference room in early July, sitting across from a shelf displaying Slurpee cups and bottles of Stewart’s Root Beer, Hiley let out a chuckle through his surgical mask. “I had no idea if we could.”

For all the talk about the cutting-edge vaccines that may just get us out of the COVID-19 mess, little has been written about adjuvants. Perhaps that shouldn’t be surprising: The late Yale professor Charles Janeway famously called adjuvants the “immunologist’s dirty little secret.”

These unheralded helpers can turn a half-baked vaccine into an effective one, or stretch a scarce vaccine supply during a pandemic. Not every vaccine requires an adjuvant, but many do: Of the more than 200 vaccines listed in the Milken Institute’s COVID-19 vaccine tracker, approximately 40 percent are protein-based vaccines, which rarely work without an adjuvant. Yet adjuvants have never attracted much funding from industry and government. “Adjuvants have been the weak link in vaccines for the last hundred years,” says Nikolai Petrovsky, a vaccine researcher at Flinders University in Adelaide, Australia. [Continue reading…]

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