“We often say that anybody who doesn’t believe that herbal medicines work has obviously never tried morphine,” Professor John Newton, consultant public health physician and Garden Fellow at The Royal College of Physicians’ garden of medicinal plants tells me. The college, a leading professional body for doctors in the UK, is also home to a garden with over 1,100 plants with links to medicine, and for good reason. “Plants have had an incredibly important role in medicine for so long, and it’s only really in recent history that doctors have rather forgotten about them. It’s often a revelation to most doctors when we take them around [the garden], and we explain quite how relevant plants are to modern medical practice,” he adds.
Notable examples include metformin, the first-line treatment for type 2 diabetes, used by over 200 million people everyday. It has roots in French lilac (Galega officinalis), also known as goat’s rue. While early attempts to isolate an active compound proved beneficial in lowering blood sugar levels, it was considered far too toxic for human use. In the early 20th century, scientists identified guanidine derivatives in the plant as the compounds responsible for its glucose-lowering effects. However, these early drugs were also soon abandoned due to their high toxicity.
A breakthrough came when researchers eventually discovered safer compounds. Among them was metformin. In the 1950s French doctor Jean Sterne revisited metformin, testing it in diabetic patients and demonstrating its ability to lower blood sugar without severe toxicity.
Other medicines commonly used today include atropine, from deadly nightshade (Atropa belladonna), which is essential in emergency medicine to increase dangerously slow heart rates. Meanwhile amiodarone, a critical medication for life-threatening irregular heart rhythms, was developed after scientists studied khellin, a compound from the toothpick weed plant (Ammi visnaga).
For asthma sufferers, as well as those with chronic obstructive pulmonary disease, theophylline – first extracted from tea (Camellia sinensis) and cocoa (Theobroma cacao) – remains an important option for treating severe asthma and lung disease, helping to relax airways when other treatments fall short. Yet beyond relaxing airways, plants harbor special abilities that can help fight one of our most pressing medical dilemmas – cancer.
Chemotherapy from plants – nature’s toxic gift to medicine
“Why do plant drugs kill cancer? We can agree that plants are largely oblivious to human suffering, so why do they make these compounds?” asks Dr Tom Prescott, researcher at the Royal Botanical Gardens Kew. He, of course, knows the answer. Plants evolved to produce these toxic molecules as defense mechanisms against predators, microbes, and environmental pressures. By coincidence, some of these chemicals have become powerful tools in modern medicine.
In the context of chemotherapies, they are exceptionally unique, down to a remarkable ability to act in such a specific way that they kill cancer cells more than they affect healthy human cells.
Madagascar periwinkle is not just pretty, it is also pretty useful.
Image credit: nlinnlin/Shutterstock.com
Among the most striking examples used today are the chemotherapeutics vinblastine and vincristine, extracted from the Madagascar periwinkle (Catharanthus roseus), a chance discovery. For decades, in communities across the globe, the periwinkle’s use in folk remedies for treating diabetes and high blood pressure had been documented, most notably in the Caribbean, where it was consumed as a tea, which got scientists curious.
After isolating the active compound and conducting extensive studies, it was found not to have a significant effect on diabetes or blood pressure. Discouraged, scientists submitted an extract to a routine screening programme, which also happened to include tests on mice with leukemia. The active compound dramatically reduced the number of leukemia cells, and today vinblastine and vincristine are effective chemotherapies for leukemia, lymphoma, breast, and testicular cancers.
Other examples include paclitaxel, from the pacific yew tree (Taxus brevifolia), discovered after a US government-funded research program. Still used today, it treats breast cancer, ovarian cancer, and non-small cell lung cancer.
Take EBC-46, for example, a compound from the berry of the blushwood tree, which only grows in a small patch of rainforest in northeastern Australia. It was first known for its ability to fight cancer, but now researchers at Stanford have found it might also help cure HIV. By flushing out hidden HIV cells and making them easier for the immune system to destroy, EBC-46 could one day lead to the first real cure for the virus.
Biodiversity loss is a terrible tragedy for mankind, for lots of reasons, but undoubtedly there will be plants that are being lost which have potential benefits.
Professor John Newton
These drugs, discovered decades ago, continue to save lives today, but more recent research has led to the development of trastuzumab emtansine (Kadcyla), a targeted treatment specifically designed for HER2-positive breast cancer – an aggressive form where cancer cells have too many copies of a protein that promotes rapid growth.
The drug works by attaching a potent chemotherapy drug to an antibody. The chemotherapy component is a synthetic version of a compound originally derived from an African maytenus plant species. The antibody portion specifically seeks out cancer cells that overproduce the HER2 protein, ensuring that the drug is delivered directly where it’s needed, rather than affecting healthy tissue. Prescott describes this combination of nature and biotechnology as working “like a heat-seeking missile”.
In his day to day research, Prescott and his team are currently conducting clinical trials on Indigenous plants in remote Papua New Guinea for solutions for common medical complaints in the region, such as tropical leg ulcers. He acknowledges that such approaches to drug discovery, often referred to as ethnopharmacology, form a small part of drug discovery approaches today, “most medicines today are discovered through high-throughput screening of libraries of [synthetic] compounds, or they’re biologics, like therapeutic antibodies,” he explains to me.
In the context of compounds from natural sources, the time-consuming nature adds to the challenges, in addition to the pertinent question of who gets to claim ownership of compounds found in nature, a dilemma that serves as a deterrent for some “in terms of commercial drug screening in industry, they don’t necessarily want to include natural products because they don’t own them. They tend to think, why spend all that money on something that you don’t own at the end of it?” Prescott points out.
For Newton, this dilemma highlights the need for publicly funded research. “What that argues for is more publicly funded discovery science to try and find them,” he says. “Taxol [the chemotherapy paclitaxel derived from the pacific yew tree], for example, was discovered through a program funded by the American National Cancer Institute, not the pharmaceutical industry.”
Climate change and biodiversity loss
Thirty-eight percent of the world’s trees are currently at risk of extinction, and according to previous estimates, only 6 percent of existing plant species have been investigated pharmacologically, and only around 15 percent phytochemically. With biodiversity declining at an alarming rate, it is possible that many species are disappearing before they have even been examined for potential medical uses.
“The problem is, if you don’t know what you will get, you’re looking for a new chemical entity from an unstudied plant. This is very difficult to predict, and if the plant is rare and you cannot source it anymore, the projects come to a stop. You will never be able to answer your question,” Michael Heinrich, Professor of Ethnopharmacology and Pharmacognosy at University College London, tells me.
But it’s not just the loss of rare, undiscovered plants. Even well-documented medicinal species are changing. “In existing medicinal plants, we have some evidence that there is a definite shift in where they can be grown,” Heinrich explains. His and colleagues’ recent review paper highlights the impact of climate change on medicinal crops, with shifts already occurring in even commonly used plants, suggesting potentially wider ecological disruptions.
“A very interesting example is lavender, which is both a medicine but also used in the perfume industry, and lavender production is now shifting to the north,” he notes. Similarly, saffron is undergoing a significant change. “Saffron used to be very successfully grown in countries like Iran and neighbouring ones. Now it’s shifting north because of climate change.”
And in some cases, plants like saffron are simply unable to adapt. “Bluntly speaking, I think the bulbs are basically boiled in the soil because of prolonged periods of heat,” Heinrich states. “Which seems to be part of the cause. Obviously, drought is another one. Long periods of drought, as we have seen in many parts of the Northern Sahel belt, and also obviously other parts of Africa,” he adds.
“Biodiversity loss is a terrible tragedy for mankind, for lots of reasons, but undoubtedly there will be plants that are being lost which have potential benefits,” Newton concludes. As he and colleagues at the Royal College of Physicians work to keep knowledge of medicinal plants alive through lectures and guided tours of the garden, their efforts reveal a profound truth – nature and medicine are deeply intertwined, a testament to the fact that before there were pharmacies, there were forests. Forests that are probably worth keeping.
