AL working on ....Deforestation jeopardizes discovery of future drugs

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  1. Ethnobiologists explore the world's shrinking tropical forests
  2. Forests – not big pharma – seem to hold the key on antibiotics
  3. Putting the "ant" into antibiotics

With more than 80,000 acres of tropical rainforest being lost everyday, could many potential drugs be lost before the plants they are derived from are even discovered?

A recent World Health Organization report shows there is a serious lack of new antibiotics in the pipeline to combat this increasing threat, which makes preserving new sources of antibiotics all the more important. Globally 700,000 people die every year because of antibiotic resistance, and by 2050 this is expected to rise to 10 million, according to a report by The Review on Antimicrobial Resistance.

Tropical forests are key because they cover less than 7 percent of the Earth’s surface yet are home to approximately 50 percent of all land animal and plant species. More than 80,000 acres of tropical rainforest and 135 species of plants and animals are lost daily, according to Scientific American.

Cassandra Quave, who studies emerging plants, 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.” One of the biggest contributions to medicine from tropical forests has been Artemisinin, an anti malarial agent used to treat malaria for which its discoverer, Tu Youyou, won the 2015 Nobel Prize in Medicine.

 

Tropical forests world map (CC BY SA 4.0)
Tropical forests world map (CC BY SA 4.0)

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. 40 percent of anticancer drugs available between 1940 and 2002 were from natural or naturally derived products.

Quinine, which is on the World Health Organisation’s (WHO) essential medicine list and used for treating malaria, comes from the bark of a Cinchona tree, 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 your eye and brain becomes damaged and can lead to vision loss. It is the second biggest cause of blindness across the globe.

However, drug discoveries from plants in this type of environment might become a thing of the past as deforestation continues.

amazon rainforest chopped down (CC BY 2.0)
Amazon rainforest chopped down (CC BY 2.0)

Partly because of deforestation, current extinction rates are 100-1,000 times higher than natural background rates and as many as 15,000 medicinal plants are under threat. This means humanity could potentially lose many future medical drugs contained within these plants. Just of the plant species we have discovered 70,000 are known to be medicinal.

Predictions vary, but only 1 – 15 percent of plant species have been screened for their medicinal potential. One study estimated that 12.5 percent of plant species documented worldwide have medicinal value, let alone other potential uses such as a food or material.

The difficult part is finding the drugs from the many plants. For every 10,000 compounds screened for medicinal properties, about 250 make it to clinical trials, according to Milken Institute Review. Of those only one will eventually become an approved drug.

One ethnobotanist and her team fighting back

Cassandra Quave is an ethnobotanist – someone who studies plants and their practical uses, using indigenous people’s traditional knowledge. She leads an antibiotic drug discovery research team at Emory University, Atlanta, Georgia.

The Quave Research Group are looking for what is called ‘antibiotic potentiators’ or ‘sensitizers.’ It can be used to take antibiotics that no longer work due to bacterial resistance and restore their effectiveness. Her team are looking for treatments for super fungus Candida Auris, which is resistant to many drugs, and undiscovered chemicals that interfere with bacterial signalling, which is is key to bacteria’s ability to produce damaging toxins. Quave says “there are actually very few chemical classes to treat fungal infections, and so that’s an area that I think deserves to be shown attention.”

Cassandra Quave in lab (CC BY SA 3.0)
Cassandra Quave in lab (CC BY SA 3.0)

She also thinks ethnobotany is “becoming more and more of a lost art.” The team she leads is rare in that it extracts chemical compounds from plants traditionally used as medicines, to produce medicinal drugs. In the chemistry lab, the team have around 1,200 extracts currently, from over 400 different species they have collected.

The plants, which are shipped in to the university, come from the south east of the U.S. – states like Georgia and Florida, and countries in the Mediterranean basin and Balkans – such as Italy, Albania and Lebanon.  However, Quave still gets out in the field. This summer she was out with students working on the Aeolian islands, off the coast of Sicily, because of the islands’ remoteness and endemic species.

While the Mediterranean Basin is a ‘hotspot‘ of biodiversity, containing roughly 13,000 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. She says “it’s frustrating, because … 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.”

 

Quave says “I think that there are lots of plants in tropical forests that have not yet been investigated, and we’re facing an alarming grade 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.”

Cassandra Quave in Sicily with plant samples (CC BY-SA 3.0)
Cassandra Quave in Sicily with plant samples (CC BY-SA 3.0). Instagram quaveethnobot

She is also concerned about the loss of culture, with indigenous tribes inhabiting many of these more remote tropical forest areas. “It is important to highlight the need to record these things [plants], and help preserve these areas, and create safe havens for these people before it’s all gone. “We use that lens of culture also in our drug discovery efforts,” and as well as plants, you lose “knowledge of how those [plants] have been used over centuries for food and medicine, and survival,” she says.

The chemical compounds extracted from some plants can be replicated synthetically, meaning, that once the compound is discovered, the plant doesn’t need to be grown in a lab. However, some chemical compounds can’t be can’t be reproduced artificially, so we are reliant on them. Quave says no compounds from the opium poppy, used for pain relief, or from the sap of the South American tree Croton lechleri, used to treat HIV related diarrhoea, have been duplicated synthetically.

In the past natural products were the major focus of antibiotic discovery programmes, but now there is a greater focus towards synthetically discovering drugs. Quave says that because these past efforts were mainly focused on soil microbes, scientists were rediscovering the same compounds over and over again. After innovations in chemistry in the 1990’s, there was a shift towards testing a lot of synthetic compounds, “with the idea that if you run enough through your system that you’ll pick up some interesting cases,” she says. “Now unfortunately, that approach has not proved fruitful.”

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