Botanists unlock the Chilean medical marvel that Charles Darwin missed

To Darwin’s modern counterparts, making firewood from soapbark would be more extravagant than using gold leaf for toilet paper. The tree, Quillaja saponaria, has become a vitally important part of the vaccine supply chain because its bark is refined into a substance called QS-21, worth as much as US$400,000 a gram.

Yet deforestation is forcing researchers to look for new ways to secure vaccine ingredients, and now researchers in Norfolk have found a way to make QS-21 in a matter of days rather than decades.

QS-21’s value comes from its use as an adjuvant: it amplifies the effects of the body’s immune response, making it a vital part of vaccines against malaria, shingles, Covid and respiratory syncytial virus. It is found in the tree’s bark, which is scraped off its trunk and then refined.

Soapbarks can be cultivated, but it takes about 25 years for a tree to reach maturity. Some companies are looking at ways to speed up the process, as the demand for soapbark means loggers now have to venture further into the Andean forests to find the trees.

Attempts to use industrial chemistry have failed, because the process yields so little QS-21. It is “a hideously complicated molecule,” said Professor Anne Osbourn of the John Innes Centre. “Fortunately, plants are chemical engineers par excellence.”

The scientists have sequenced the 30,000 genes in the Q. saponaria genome and can transfer the genes into a much faster-growing plant – Nicotiana benthamiana, a relative of tobacco.

“When the [soapbark] genes are inside the [tobacco] plant cell, they can use all of the machinery of the plant cell to do what they do,” said Osbourn.

The plant acts like a chassis, “so it’s a very quick and powerful method of testing gene function. We can test a single gene on its own, or we can test combinations of genes. It’s incredibly efficient.”

So far Osbourn’s team has produced only small amounts of QS-21 using a few dozen plants in the lab. “There is a lot of optimisation to be done,” she said. But this platform offers a further exciting opportunity. “What we’ve done for QS-21, we can now apply across all available genome sequence information for the plant kingdom.”

Scientists have sequenced about 5,000 plant genomes out of the estimated 400,000 plants on the planet. The JIC team is now scanning through those genome sequences to spot genetic instructions that might be involved in making other medicines.

“[We are] drawing on the chemical engineering capabilities of the plant kingdom to make next generation therapeutics,” Osbourn said. “Natural products are a great source of medicines because they’ve been used for thousands of years by humans.”

Although Darwin may not have grasped soapbark’s significance, understanding the role of natural selection is important in realising how to unlock the potential for plants to create new medicines.

Plants do not make substances such as QS-21 “just for fun”, Osbourn said. “For a plant, it’s expensive [in energy] to make these molecules. They’re doing this because these molecules have some sort of role in ensuring or enabling survival of plants in their natural environment. If you can unlock the chemical engineering capability plants, you can get to a whole swathe of chemistry that hasn’t been accessed before.”

Photograph by Dr John A Horsfall/Getty Images, HP Robinson/Bettmann Archive/Getty Images