‘There are lots of plants in tropical forests that have not yet been investigated, and we’re facing an alarming rate of deforestation’ – Ethnobotanist Cassandra Quave
It’s well-established that deforestation is contributing to climate change, but its effect on the discovery of new drugs is less understood.
A recent World Health Organization report warns there’s a critical lack of new antibiotics in the pipeline to combat the threat of antibiotic resistance. Globally, 700,000 people die every year as a result of antibiotic resistance. By 2050 this is expected to rise to 10 million according to a report by The Review on Antimicrobial Resistance, which was commissioned and supported by the UK Government and Wellcome Trust (although operated independently.)
But scientists believe tropical forest plants and animals could be a source of new antibiotics to replace the current stock.
After the so-called ‘golden age’ of antibiotic discovery in the 1950s and 60s, scientists appeared to have exhausted the possibilities of the actinomycetes – a bacteria from which many antibiotics can be formulated. Researchers then moved on to new methods by creating chemical compounds in a lab.
However, billions of dollars later, that didn’t bring the results pharmaceutical companies had hoped for. Many of them abandoned work on new drugs in favor of the guaranteed profitability of improving existing ones.
But a combination of over-prescription, people not finishing their course of antibiotics, which leads to antibiotic-resistant bacteria, and lack of new drug discoveries has caused a rise in antibiotic resistance. This has prompted a renewed interest in deriving new drugs from natural products, often from largely untapped environments, as this piece in the Toronto Star showed.
Forest as pharmacy
Drugs used to treat malaria, cancer and glaucoma all originally came from tropical forests and around 120 prescription drugs sold globally originate from rainforest plants. Forty percent of anticancer drugs available between 1940 and 2002 were made from natural or naturally-derived products.
Quinine – which is on the World Health Organisation (WHO)‘s essential medicine list, and used for treating malaria – comes from the bark of a Cinchona tree, which is found in the tropical forests of the Andes, South America. And from the Calabar bean, originating in the tropical forests of Africa, comes the drug Physostigmine, which is used to treat glaucoma – a condition where the nerve that connects the eye and brain becomes damaged and can lead to vision loss. It is the second biggest cause of blindness across the globe.
However, with more than 80,000 acres of tropical rainforest and 135 species of plants and animals being lost daily, (according to this report in The Scientific American and attributed to the FAO) extracting drugs from this environment might no longer be possible in the near future.
Cassandra Quave is an “ethnobotanist” — a scientist who works on drugs derived from plants. She says: “You have mega-corporations just destroying these forests, [while] scientists like myself have great difficulty in even accessing these biological resources to study them before they’re gone.”
Partly because of deforestation, current extinction rates are 100 to 1,000 times higher than natural background rates and as many as 15,000 medicinal plants are under threat, according to botanical gardens group BGCI. Of known plant species, over 28,000 are recognized as medicinal, and many have other potential uses including as a material or food. Predictions vary, but so far less than 15 percent of plant species have been screened for their medicinal potential.
The difficult part is finding the drugs from so many plants. For every 10,000 compounds screened for medicinal properties, about 250 make it to clinical trials, according to the Milken Institute Review. Of those, only one will eventually become an approved drug.
Ethnobotanists fight back
Ethnobotanist Quave, who studies plants and their practical applications using indigenous knowledge, describes her endeavors as a “lost art.”
She leads an antibiotic drug discovery research team at Emory University, Atlanta, Georgia. The Quave Research Group is looking for ‘antibiotic potentiators.’ These can be used to restore effectiveness to antibiotics that have been rendered impotent by bacterial resistance. Her team is looking for treatments for super fungus Candida auris, which is resistant to many drugs.
Quave also wants to draw attention to curing fungal infections, as she says there are few chemical classes that currently treat them.
The team she leads extracts chemical compounds from plants, traditionally used as medicines, to produce drugs. Most pharmaceutical labs now synthetically make the chemical compounds from which drugs are derived. But the Quave Group takes the natural approach: her team now has around 1,200 extracts from more than 400 different species it has collected.
The plants shipped in to the university come from south-east U.S. states like Georgia and Florida and countries in the Mediterranean basin (critical ecosystem partnership fund) and the Balkans, including Italy, Albania and Lebanon. However, Quave still gets out in the field. This summer she was out with students working on the Aegadian islands, off the coast of Sicily, because of the islands’ remoteness and endemic species.
Quave says she would like to be able to study plants from tropical forests too, but that it’s very difficult to get permits to take plant samples from countries in this environment.
“I think that there are lots of plants in tropical forests that have not yet been investigated, and we’re facing an alarming rate of deforestation in tropical forests, due to mining, logging and gold and natural resource extraction that’s just destroying large tracks of land … tropical forests are definitely one of those high risk areas where we are rapidly losing those resources for drug discovery.”
She is also concerned by the loss of collective memory from indigenous peoples who have used medicinal plants for thousands of years.
“We use that lens of culture also in our drug discovery efforts … knowledge of how those [plants] have been used over centuries for food and medicine, and survival,” she says. “It is important to highlight the need to record these things [plants and knowledge of their use], help preserve these areas, and create safe havens for these people before it’s all gone.”
Putting the “ant” into antibiotics
A microbiologist at the University of East Anglia, Matt Hutchings, is leading a team looking for sources of antibiotics in the nests of leafcutter ants which live in the rainforests of central and South America. Leafcutter ants could provide major breakthroughs for new antibiotics. The last natural product antibiotic to be introduced was daptomycin, discovered in 1987, so new drugs are desperately needed.
He works with Acromyrmex echinatior leafcutter ants collected in Gamboa, Panama. The ants gather leaves in the rainforest and feed them to a fungus known as Leucoagaricus gongylophorus, which in return supplies them with food. Antibiotic-producing bacteria which live on the ants, known as actinomyces, are the raw material for 60 percent of known antibiotics. The ants feed the bacteria living on them through specialized glands in their exoskeletons and use the antibiotics produced by these bacteria to kill off other microbes that would otherwise infect their fungus garden. If the ants smell infected parts of the fungus they remove it, dump it away from the nest and use antifungal antibiotics to sterilize it. Ant species that farm fungi (Attini ants) have most likely been using antibiotics for more than 50 million years to protect these fungus gardens from pests.
‘They’ve been giving antibiotics out like [candy], which is the worst thing you can do.’ – microbiologist Matt Hutchings
The team Hutchings leads is isolating bacteria from the ants, and seeing if the antibiotics they produce prevent other harmful bacteria from growing. He says the team has identified antibiotics which could be very powerful against ‘superbugs’ like MRSA, (methicillin-resistant Staphylococcus aureus) which has been a serious problem in hospitals.
And while Hutchings believes only 10 percent of the antibiotics that are made by actinomyces have been discovered, leaving huge room for potential, he says the problem boils down to money: “Who wants to invest billions of dollars to find new antibiotics? Drug companies don’t want to pay for it. Governments can’t afford to pay for it. Antibiotics don’t make any money, basically.”
Hutchings says while the antibiotics we have are effective, we have used them badly. “They’ve just been giving them out like [candy], which is the worst thing you can do.”
He hopes we’ve learned our lesson now, “so [that] when we develop a new generation of antibiotics, they’ll be used very carefully.”
- The London Science Museum is holding a major exhibition about antibiotic-resistant bacteria called Superbugs: The Fight for Our Lives, which runs until spring 2019. See Harry Ridgewell’s report on the exhibition and the fight against antibiotic resistance.