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A living laboratory: San Diego Botanic Garden embarks on a new scientific journey

Drug discovery in plants has generally been hit-or-miss, with scientists cutting samples from living species, then drying them out and taking them back to the lab to see what kinds of interesting chemical compounds they contain.

While that approach has filled mankind’s medicine chest, many believe that it has missed much and that a holistic approach, one informed by Indigenous traditions, can yield a far-greater spectrum of interesting and potentially beneficial substances with medicinal potential.

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A new collaboration between San Diego Botanic Garden in Encinitas and several local research institutions aims to go deeper by creating a kind of living laboratory, one capable of teasing out nuances that simply snipping away has missed.

The garden just received a $384,000 grant from The Conrad Prebys Foundation to create a world-class medicinal plant collection and to develop a model for how best to grow research opportunities through careful cultivation of everything from local lemonade berry to ephedra, a Chinese herb already widely used in existing medications.

Ari Novy, the garden’s president and a plant evolutionary biologist with a doctorate from Rutgers University, said the biggest mistake is to look at plants as groups based on their species and subspecies, rather than as individuals. Factors from growing conditions to genetic makeup mean that no two plants are ever identical, and all have evolved vast chemical toolboxes to help them cope with a stationary existence.

“We’re talking about tens of thousands of chemicals per plant in order to cope with the changing environment in order to cope with the fact that they’re rooted and can’t escape,” he said.

A Torrey pine tree, one of the rarest pine trees in the world, at the San Diego Botanic Garden in Encinitas.

A Torrey pine tree, one of the rarest pine trees in the world, at the San Diego Botanic Garden in Encinitas. The resin from the tree was used by Native Americans for colds, sore throats, and wound dressings.

(Hayne Palmour IV / For The San Diego Union-Tribune)

But it’s not as easy as simply finding a better way to detect the presence of chemicals.

“Plants are not always producing all of the chemicals they can produce,” Novy said. “Many only produce certain chemicals in very specific and small localized regions of their tissues and organs and may only produce certain chemicals at certain times of the day or season of the year or during certain environmental conditions like heat stress.

“A big part of what we’re trying to do here is say, ‘we’ve not yet made the effort yet to look at the totality of chemicals a plant can make.”

To some extent, this effort seeks to further quantify what Indigenous people have known for millennia. In acknowledgement of the traditional use of local plants, the garden has a long-standing collaboration with the Jamul Indian Village, one that started 20 years ago with the joint creation of a “Native Plants and Native People Trail” inside its larger 37-acre property on Quail Gardens Drive.

Lisa K. Cumper, tribal historic preservation officer for Jamul, said the community sees the latest effort as both furthering traditional uses of local medicinal plants and one that preserves that knowledge for the future.

“Our native flora is among the richest and most diverse in the United States,” Cumper said via email. “We hope to teach our traditional and medicinal uses of the flora from the coast, into the mountains and to the desert.”

That statement is well supported. San Diego is the most biologically diverse county in the contiguous United States, according to The Nature Conservancy, a global environmental nonprofit.

Many indigenous people have been tending to medicinal plants for longer than the United States has been a nation, and experts say that a living collection is essential to the discovery process.

Changing growing conditions in systematic and repeatable ways, and properly maintaining control groups for comparison, is key to a deeper understanding of the true universe of possibilities lurking even in species that may have already been thoroughly studied.

Ephedra, a stimulant, is used to promote low-blood pressure and as a decongestant.

Ephedra, a stimulant, is used to promote low-blood pressure and as a decongestant.

(Hayne Palmour IV / For The San Diego Union-Tribune)

“Maybe we’re going to purposefully heat-stress or drought-stress the plants in order to elicit them to produce a greater diversity of chemicals,” Novy said. “Maybe we’re going to harvest tissues such as living root tips that haven’t typically been harvested in the past.”

There is significant interest from San Diego’s diverse biomedical research community. Initial partners in the project include Sanford Burnham Prebys Medical Discovery Institute, the San Diego branch of the Ludwig Institute for Cancer Research, UC San Diego, Ionis Pharmaceuticals, SRI (formerly Stanford Research Institute).

At the moment, there are a few plants already tended at the garden that are on the radar for initial investigation. San Diego Botanic already maintains one of the best collections of ephedra plants in the world. Acquired from a botanist who followed scientific protocols to the letter, they have enough information already on record to provide a good test bed for deeper study.

Others, such as the native and endangered Torrey Pine, have long been thought to have interesting medicinal qualities, but have not received much holistic study. Another example of a local that needs a deeper look, he said, is lemonade berry, known to be rich in vitamin C, but also a possibility for other substances that could end up benefiting pharmacopeia.

The berries of a lemonade berry plant, a native plant in Southern California, at the San Diego Botanic Garden in Encinitas.

A lemonade berry, a native plant in Southern California, at the San Diego Botanic Garden in Encinitas. Native Americans ate the berries, which are high in vitamin C, and used it to make a beverage.

(Hayne Palmour IV / For The San Diego Union-Tribune)

“These plants that live in our arid environment are leveraging all kinds of interesting chemicals to deal with the challenges of living in difficult conditions and poor soil,” he said.

Several local plants have been historically used by the Kumeyaay for medicinal purposes, including elderberry, Cumper said.

Known as “kepally” in the Kumeyaay language, the flowers from this plant can be dried and used as a vitamin-rich tea to support the immune system and reduce fevers. After boiling the berries to remove toxins, the fruit can be used to reduce joint pain, and boiled bark is used for healing open wounds.

White Sage — or pellytaay in Kumeyaay — is used ceremoniously by many Indigenous tribes to cleanse the spirit through the burning of leaf bundles, but the leaves can also be used to treat the flu or common cold, Cumper said.

Cumper hopes the project brings more visibility to the history of the Kumeyaay people in present-day San Diego County.

“I hope that it will benefit the tribe by letting the community, visitors and general public know that the Kumeyaay are still here and that our history in San Diego has been here since time immemorial,” she said.

Resin oozes out of a Torrey pine tree trunk at the San Diego Botanic Garden in Encinitas on Friday, March 11, 2022.

Resin oozes out of a Torrey pine tree trunk at the San Diego Botanic Garden in Encinitas. The resin was used by Native Americans to treat colds, sore throats, and wounds.

(Hayne Palmour IV/For The San Diego Union-Tribune)

Of course, drug companies seek to discover and transform intellectual property, a reality that has caused disputes in the past. If valuable compounds are discovered, who owns them remains an as-yet-unanswered question.

Novy said the consortium intends to operate, at least at the outset, under a general understanding that benefits accrued will be shared and not just with the garden but also with indigenous populations. Exactly what that would look like, though, has been left intentionally vague. Getting lawyers too involved so early on could stop anything from moving forward.

“What we don’t want is to pre-decide that question in a way that is not servicing the ultimate goal, which is to help create therapeutics that benefit humanity,” Novy said. “At the same time, if there are commercial benefits that are coming out of our collection, and some portion of that could help support the maintenance of this collection and use of it in the future, that might be smart.”