Hunting for Medicines Hidden in Plants

"In recent decades, with the advance of high-tech methods for synthesizing molecules, the search for useful medical compounds from the natural world, especially plants, has faded. Fortunately, just as we've started to recognize the limits of artificial synthesis, even newer technology is now helping scientists like me to release more of nature's medicinal secrets.

Plants have been the source of countless revolutionary medicines since the 19th century. Scientists derived aspirin from the willow tree, for instance, and morphine from opium poppies. They found quinine, the first treatment for malaria, in the bark of the Amazon's fever tree (and more than a century later, scientists in China found that artemisinin from sweet wormwood was also a powerful anti-malarial agent). Many groundbreaking cancer drugs also came from plants -- Taxol from the Pacific yew tree, vincristine from the Madagascar periwinkle.

Microbes found in soil and fungi launched a golden era of advances in antibiotics, starting with the discovery of penicillin in a mold in 1928. By the peak in the 1950s, scientists were isolating a wide range of antimicrobial compounds from microbes found in nature. But such work ended all too soon, as scientists stopped discovering effective new compounds.

Many of the drugs originally drawn from nature are now synthesized in pharmaceutical factories, using the blueprint of their chemical structures. Natural products (that is, chemicals genetically encoded and produced by living organisms) account for more than 60% of the pharmaceuticals that we possess.

Over the past 30 years, however, the focus on nature waned as scientists instead built large chemical libraries filled with tens of thousands of lab-made molecules. One hope was that the next antibiotic breakthrough would emerge from making and testing enough of these synthetic compounds. But that effort has fallen flat: Though other medicines have been developed in the lab, no new registered classes of antibiotics have been discovered since the 1980s.

Now a post-antibiotic era looms, a time when infections have evolved to make current medicines ineffective. Globally, an estimated 700,000 people die each year from antimicrobial-resistant infections. In 2016 a U.K.-sponsored commission projected that figure would increase 15-fold by midcentury.

The lesson is clear. To harness the great untapped medicinal potential of nature, we desperately need access to the chemical blueprints of these molecules in the wild. There are an estimated 374,000 species of plants on earth; records exist for the medicinal use of around 33,000, or just under 9%. While some of these plant-based medicines have been preserved in books -- like De materia medica, by a 1st-century Roman physician -- many others exist only in oral traditions, practiced by long lines of shamans or medicine men and women, often to treat bacterial infections.

 

Incredibly, only a few hundred plants, at most, have been subjected to rigorous investigation under the lens of modern science. For the most part, we don't know if they work, how they work, whether they're safe or which compounds are responsible for their medicinal properties.

 

There are barriers to discovery. Studying compounds derived from living organisms is incredibly complex. Aromas emitted from crushed leaf tissues or nectar-rich flowers are the result of a mixture of hundreds -- or even thousands -- of unique molecules present in specific ratios. It's an evolutionary perfume blend crafted by the plant to defend against predators or attract pollinators and seed dispersers.

 

Unlike modern medicine, which relies on single compounds designed to target a single receptor type or pathway in the body, nature largely relies on many compounds hitting many targets to yield the desired outcome. Testing all of these compounds is an extended hit-or-miss enterprise -- which is one reason that scientists have tried to speed up the process by designing molecules in a lab.

 

Thankfully, things are beginning to change. Advances in analytical chemistry techniques have revealed new ways to interpret these complicated chemical signals of nature. For example, a new technology that uses electron microscopy under ultracold conditions has revealed precise chemical structures of microcrystals from tiny amounts of material. New molecular networking platforms infer how the structures of compounds in complicated mixtures are related by crunching data about the precise mass of each molecule. Nuclear magnetic resonance can characterize the structure of known and new molecules.

These tools are becoming more sensitive each year as the technology advances, even helping scientists to capture the detailed features of molecules found in minute quantities in nature. The leaps forward in chemistry over the past decade are opening up windows into the vast landscape of natural products never before seen or studied. History may record this century as the moment when scientists learned to read the language of nature.

But this also is a century in which we are losing biodiversity at least as fast as we can study it. In 2020, I was one of 210 scientists from around the world that contributed to the U.K. Royal Botanic Gardens' Kew report on the State of the World's Plants and Fungi. Things don't look good: Two in five plants are thought to be threatened with extinction. We face a biodiversity crisis just as we most need nature's resources to secure the future of our food supply and the next generation of medicines.

To apply our advanced new tools to the exploration of nature, scientists need access to vast reservoirs of biodiversity. Navigating the bureaucratic hurdles of the international agreements governing such research can be intimidating, however, to scientists in academia and industry alike. Thankfully, U.S.-funded initiatives have opened up access to a treasure trove of natural products collected under international agreements -- over 150,000 extracts now available to scientists searching for the next chemical blueprints to fight the diseases of our time.

Nature's next gifts may include new lifesaving antibiotics, cancer therapies and nonaddictive pain-relievers, but reaching this new golden era of medical discovery won't be easy. We have to keep trekking through the swampy muck to uncover nature's secrets." [1]

1. REVIEW --- Hunting for Medicines Hidden in Plants --- New technology is helping to unlock the secrets of the natural world, just as the limits of synthetic remedies are becoming clear.
Quave, Cassandra.  Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 20 Nov 2021: C.4.