December 7th, 1941, a surprise Japanese aerial attack on the American Naval Base at Pearl Harbor in Hawaii initiated the formal entry of the United States into the second World War. Thousands were killed. The damage was extensive. In addition to those that died that day, the Pearl Harbor attack led to a far greater loss of life amongst the Allied forces. Since the start of the war, malaria had
ravaged forces stationed in the West Indies. Only held at Bay by a wonder drug from the Dutch East Indies modern day, Indonesia. The source of this plantations of the humble Cinchona tree on the Island of Java, where 90% of the world's Quinine was sourced. Demand for this plant based
malaria cure roared during wartime. But by crippling the Allied defense through the bombing of Pearl Harbor and the capturing of Singapore, there was nothing to stop the Japanese from taking Java and cutting off supplies to their enemies in the West In the effort to acquire the island's rich oil fields, Japan also denied its opponents one of the most crucial medicines in human history, and scientists were forced
to seek out an alternative to the substance that had enabled Western colonization of the tropics for centuries.
Cinchona has been called a tool of imperialism and that's because Quinine, which is the active antimalarial chemical found in the bark, was so important for empire, particularly across 18th and 19th century.
Today, we find out how plants and medicines have changed the fortunes of nations, and their roots from forest to pharmacy throughout history. We'll hear how the hunger for cures has transformed landscapes, seen powers rise and fall, and altered human history forever.
Quinine started to gain extra significance for them. So to be able to control the quality and quantity of supply became very important. Plantations started to be grown in British India and Dutch Indonesia.
And we'll hear what we can learn and how lives can be saved in the search for modern day medicines.
Plants are actually brilliant chemists.
I'm James Wong, and welcome to Unearth Mysteries from an unseen world from Royal Botanic Gardens, Kew. Today, I'm finding out how one kind of tree changed the course of world history. The cinchona tree is native to South America. Myth has it that in 1630, the Spanish Countess of Chinchon
visited Peru and fell ill with a fever. The substance given to cure her was the bark of cinchona, which we now know contains many useful substances, only one of which is Quinine. And whilst the real story of how cinchona's healing properties first made it into medicine, remains a mystery, there are plenty of clues to help us piece together some
of that history. The Royal Botanic Gardens, Kew has one of the largest collections of cinchona bark in addition to Herbarium specimens and a wealth of historical records from the 19th century when Quinine was transported around the world. It's this archive that makes Kew, so compelling for my first guest.
I'm Kim Walker, and I am a PhD student at Kew. And I work in the Economic Botany Department and I study that collection of cinchona bark. It does sound a bit dry, doesn't it studying bark? But actually if you're going to pick a bark, this is probably one of the most interesting ones in history. Cinchona bark contains Quinine which for over 300 years was the only known
malaria treatment in Europe. And also is the flavoring in everybody's favorite cocktail, the gin and tonic, because it is the flavoring and tonic water.
When we talk about malaria, it's quite difficult to picture a world before cinchona bark was in existence, because malaria wasn't something that was just found in remote location.
Yeah, absolutely. So it's just slightly out of living memory now. So not many people realize that we used to have malaria and Britain all the way up to the first World War.
So tell me about the history of cinchona bark. How do we know that it contains Quinine and that that's an effective treatment for malaria?
That's a really interesting question because when the Spanish entered South America, which is where cinchona comes from originally, across the Eastern slopes of the Andes, before this period, malaria, or at least a very severe forms of malaria didn't exist.
So as the Spanish come in, bringing malaria with them, and Cinchona trees already grow South America is not very clear who or when somebody connected that cinchona bark kills malaria. But it's likely that it would have been indigenous healers, had
really superior knowledge of local botanics and healing. And so at the (inaudible) , as it were, where new diseases were entering the country and cinchona may have already been in use for other things, they would have put two and two together and found the treatment. We do know that was around about 1600. And by about the mid 1600s cinchona bark started being imported into Europe.
Is this presumably because cinchona bark was really important for industry at one point in time? People wouldn't be able to conduct business across large parts of the world, if you couldn't physically access them while staying healthy.
Absolutely. So cinchona has been called a tool of imperialism and that's because Quinine, which is the active antimalarial chemical found in the bark, was so important for empire, particularly across 18th and
19th century. And so, for many different countries within Europe who are interested in expanding into new territories and colonizing areas, such as India and parts of Africa, Quinine was really important because unless you can control disease, whenever you were to go somewhere that may have something like malaria, you're more likely to die off than to be able to enter those places.
How is Quintin traditionally administered? Was it administered in tonic water?
Tonic water came a little bit later in the 19th century, which is about the mid 1800s. But originally how Europeans started to use cinchona was in very traditional ways to use medicine, which is getting the bark, which is a very tough material, grinding up into a powder. So you can crack open all the plant cells and get the
chemicals out, and then dilute it. And the best way to dilute and extract chemicals quite often is by using a bit of alcohol. So early ways to dilute it would have been using wine, or port, or perhaps stronger spirits like brandy. By the 19th century, it was one of the largest imports of American drugs imported to Europe. Demand started to outstrip supply, and it started to be over
harvested in the world by some unscrupulous harvesters. And as this happened, and as the 19th century grew older and different empire started to look further afield to colonize new areas, Quinine started to gain extra significance for them. Around the early 1900s, different countries, particularly the Dutch and the British, started to look into how they could get hold of
this tree for themselves to cultivate. Quinine was used all the way up to the second World War, when supplies from Indonesian plantations got caught off. Unfortunately, using Quinine to control the ability to colonize the areas is not a very nice thing to think about. And for the British and the Dutch to get hold of these trees, they were going to have to basically smuggle them out of South America.
And they were justifying that as saving the seeds because of over harvesting, which is very complicated, because really nowadays you wouldn't do that. You would work with communities to bring up the cinchona bark and make it available for everybody if they chose to. Everything was different then. And unfortunately, they smuggled out to make plantations in India and Indonesia.
So in that time, that was really considered par for the core. So people wouldn't have raised an eyebrow at all about the idea of taking plant material for one part of the world, or taking the knowledge of plant material even, and applying it for themselves. But nowadays we actually have a term for that bio- piracy and the same way that you would pirate a bootleg CD or a copy
of a film that you download off the internet. We would have the same term for biological genetic information, and also information about how to grow and use plants. Now I should just point out here that Kim's book, Just the Tonic a Natural History of Tonic Water, which she co- wrote with Mark Nesbitt, is a fantastic read. If you'd like to delve a little deeper into the rich history of
this favorite tipple, then check it out. The Cinchona story is just one example of how a naturally occurring medicine played an essential role in the movement of people internationally.
With the current conversation about the British empire and its legacy, it's fascinating to me to contemplate whether European powers would have been able to colonize the world's tropical regions to the same extent, if at all, without this wonder drug. Or would history have unfolded quite differently? It's amazing to think that this humble tree might have carried the
course of history upon its delicate branches. Nowadays, scientists are investigating new substances that can be created using other alkaloids within cinchona bark. And while science is opening more doors to plant medicines every day, they are still a constant
source of novel, unexpected compounds. I chatted to Dr. Bente Klitgaar, Senior Research Leader in Identification and Naming and Head of the Americas Department at Kew. She's mostly based in the Herbarium where seven million plant specimens are held. Her team looks after the two million of them from the Americas. My first visit to Kew's Herbarium was 15 years ago
now, and I was just starting on my master's. And it's quite difficult to picture what seven million samples is like. But to me, it was like going into a scene from Harry Potter, just floor after floor in this beautiful old Victorian building, of course, with some modern adjuncts now. And a Herbarium is to an untrained eye, just millions of pressed flower specimens.
They are.
It's like some kind of someone's hobby just went really out of control. Why is it important to have so many just pieces of plant squished between paper?
They are the ultimate evidence. Because we don't just have one of each plant species, we have about 80% of the biodiversity in terms of the generic level, which is a bit scientific, represented in Kew's Herbarium. So, Kew's Herbarium is one of the best global collections in the world. And as I said, we can use it for any type of research, because we don't have to have all one
of each species, we have the whole distribution range. I have some plants that I have known ever since I started my career in botany. And these are the legume family that I have been specializing. I've been doing many things in my career, but the legume family has always been part, been my friend all the way along.
So peas and beans, the legume family. It's such a massive family. And this includes everything from tiny little herbs in the Arctic Tundra-
Exactly, yes.
... right up to giant Amazonian trees.
Yes. Some of the biggest emergence in the Amazon are legumes as well. So I'm going to show you some of my very, very best friends and my first legume friend. It's a genus called Brownea. When I started working on this genus called Brownea, they're rainforest trees. They occur only in Northwestern, South America. And I can show you-
Wow, look at that.
Yeah. Yeah. So, at Key, we are very, very lucky. There's one in the Palm house, which is Brownea Coccinia, and there's one at Princess or Wales Conservatory called Brownea grandiceps. So when I miss them, I can go into one of these green houses, and they flower as well, they're fantastic. They get up about a football size.
It looks like something straight out of the movie Avatar. It's like a giant pompom flower with these really, really long filaments that are coming out of it.
Yeah.
Almost like you've got a big fistful of the showiest rhododendron and stuck them all together-
Exactly.
... and just made them look even more exotic.
As a young scientist, I decided to work on this group for my Master's thesis. So I went then and my task was to understand that the Brownea is species in Ecuador. That was one task, and the other task was then to understand how the Brownea species were used in Ecuador. And I wanted to write a book about children who live in the rainforest. So I actually got
myself a deal with a publisher. And I went and visited some indigenous communities in the Amazon at the same time. So I realized-
Talk about multitasking there. Is there anything you can't do?
I try and spoil it. But some indigenous tribes in Northern Ecuador, they actually use one Brownea, a species of Brownea, grandiceps, as a contraceptive. And I did lots of literature work. And I realized that actually several species had been used by other indigenous tribes in Colombia, in Venezuela, and in Ghana. So it's not, it wasn't an isolated phenomenon. None of the families have
more than four children. The legume family members of the family, or members of the legume family, it's been shown that they are the only family to contain a group of chemicals called flavonoids, or isoflavonoids. And these flavonoids or isoflavonoid, they've been found in a species of clover called trifolium subterraneum. They have this estrogenic effect.
Having clues like this from naturally occurring compounds can get scientists really excited, as it offers possible clues for building affordable, safe, and sustainable alternatives for human use in a lab. Bente explained why research like hers is so vital in the first place.
It has proved my viable. It has proved viable that you found one compound in one plant that is protective against cancer. And you can start to synthesize that part, but you wouldn't have found that compound had you not found it in a plant first.
And that covers everything from some of the most important cancer drugs used in conventional medicine-
Yeah, yeah.
... to the leading treatment for malaria.
Exactly. Exactly.
So want to know is, did you ever write the children's book?
Unfortunately, I got very sidetracked by the science.
Thanks for listening to Unearthed. I'll be back again in just a minute. But first here's a message from our supporter, Kim Catrall.
As a charity, the Royal Botanic Gardens, Kew is facing a severe funding crisis right now. The impact of Coronavirus has created a financial shortfall of 15 million pounds. This money is vital for the upkeep of these beautiful botanic gardens and crucial to continuing its global conservation work. Plants and fungi hold many of the answers to the world's biggest challenges, such as climate change, food security, and biodiversity
loss. And Kew needs to play a role in furthering the science and identifying desperately needed solutions. If there's one positive thing that could come out of this pandemic, it will be to encourage each and every one of us to look afresh and with urgency at these global challenges. If you are enjoying this podcast, and feel inspired by
the work that Kew does, please go to Kew. org to donate today, to help not only protect Kew, but also preserve the future of our planet.
A really exciting area of Kew's modern day remit, lies in the evaluation of plants. And this can mean traveling far and wide to learn about new species, as well as how they're being used by local people.
I'm Tom Prescott, and my job title is Evaluation of Plant Uses. I'm mainly focused on looking for potential medicines from plants and fungi. So I first fell in love with Papua New Guinea, kind of, I was working in Australia and I decided to kind of go up there and have a brief look. And then later on, when I managed to start to get field work funding from when I was an undergraduate, I started to go there.
People walk around barefoot and you have to. I'm quite convinced of the idea actually, that if you live in the rainforest permanently shoes are of very little value to you. And the reason is that, just going about your day to day business, walking across rainforest terrain, you need that sort
of tactile feedback from your feet. So for example, when you're walking along, there's lots of deep ravines where the little rivers at the bottom and you walk over essentially tree trunks, from trees that have fallen over that act like a bridge to walk across. But the downside is if you get kind of scratched by something on your ankle, in a rainforest environment, it gets infected really quickly.
After experiencing an infection himself, Tom became deeply interested in how local plants were being used to treat them. Fortunately, the antibacterial, or antimicrobial properties of some plants are there to help tackle infections before they get serious.
My interest is the plant medicines that are used to treat these cutaneous ulcers, so skin ulcers, which are really common there. They're quite debilitating, and because they go deep into the tissue, they're really, really painful. There's a kind of more serious side to it, which is that they act as a possible gateway for secondary infections. So there's
another kind of bacterial infection caused by Treponema bacteria. And it's sort of believed or theorized to be the case that once you have one of these little skin ulcers, that all the kids have gotten these villages, the Treponema bacteria can then get into your body. And Treponema causes something called Yaws Disease. And that that can have really horrific consequences. It's not uncommon for plants to produce anti-
microbial substances. And then people who live in rainforests have adapted to their environment, by learning which plants to use, to put onto these infected skin ulcers. Eighty percent of people in Papua New Guinea live in rural areas, and when we say rural, we don't really mean people driving around in Land Rovers in Devon. We mean people living
right out in really hard to access areas. The one thing that a plant medicine has that can really win over a conventional pharmaceutical treatment. And the one thing that has that will basically beat the other treatment hands down every time, is it exists in the field, and it's constantly there.
Tom's fascination with local medicines available in the Papua New Guinea rainforest led him to run trials, comparing how these anti- microbial plant treatments with the sorts of things you can buy over the counter in the UK. We had a serious geek out about this. This is knowledge that people in societies all over the world have potentially had for decades, 100s, maybe even 1000s of years. But it's only
being reported scientifically now. And skin ulcers are something that affects millions of people worldwide. So if there's an ability to find a treatment for them, that is somehow more effective, or either as effective as conventional therapies, then there's some real massive potential benefit to humanity here. What have we found so far?
The most promising plant that we've been looking at is something called Ficus septica, which is a species of tropical fig. And also a crucial point here is that we're looking for the most common anti- microbial plant that we can
find. The rationale is that we want to find clinical evidence to support the use of a traditional medicine, but the traditional medicine should be so common that anybody in any village, virtually in lowland Papua New Guinea, you could just walk 50 yards and find this plant, and use it anytime they want to. Ficus septica has really good antibacterial activity. It produces lots and lots of little figs, sort of
like berry like things. And if you walk up to Ficus septica, which is a small tree, and you can find it kind of growing pretty much anywhere in lowland Papua New Guinea, you pull off one of these little fruit like things, and then this really beautiful white sap starts dripping out of the end of the berry. And
the sap contains all these anti- microbial compounds. And what you notice as it produces a slight sort of reddening around where the sap has been, nothing too extreme, but as if there's a little kind of immune response coming back, which is quite interesting. But the other thing that the plant sap does that we've seen really clearly is it forms a kind of flexible plastic kind of covering over
the wound. There are flies that are attracted to these wounds and they're believed to be transmitting bacteria. And I've noticed this when I first had one of these infected wounds, they make contact with the sap, it's almost like they get a physical shock and they jump straight back, and they won't go within a few millimeters of it.
So you have the anti- microbial response, which gets rid of the infection, potentially it reduces your body's reaction to that, the inflammation, which can cause a lot of pain. It then seals the wound and also prevents secondary infection from insects. That's nuts, like four different things all in one plant.
Yeah. I was pretty surprised to see all of this. I think there is a lot more out there in the rain forest that's waiting to be discovered.
It's so exciting to me to hear how the botanical world is still offering new scientific surprises, and helping us find solutions to old problems as we share knowledge around the world. It makes you wonder what other undocumented answers lie within the realms of our forests, hiding in plain
sight. From rainforest now to a forest of information. In addition to Kew's living collections of medicinal plants, the economic botany collection, or ECB, holds around 25, 000 items of medicinal plant materials, including the Royal Pharmaceutical Society's collection of medicines, as well as Chinese traditional medicines. I found out how we're working with plants to make medicines today with Dr. Melanie- Jayne Howes.
So my name is Melanie Howes. So I lead research in phytochemistry and pharmacognosy at Kew. So much of my research currently involves investigating the chemistry of plants, but especially to understand their uses as medicines and also for our health, such as in our diets.
It's very easy to assume that the uses of plants in medicine is a historical anecdote. They were very interesting in the past, in the Roman empire, but in modern pharmacology, they're not used to the same extent. How accurate would you think that common belief would be?
We have so many examples of pharmaceuticals, which were originally discovered from plants. So some of these are the original chemical that was derived from the plant itself. Some of them are derivatives. And some of them, we use the plant chemical to inspire us, to design a brand new medicine. And we have many of these examples available in
clinical use currently. So for diseases such as dementia, cancer, heart disease, malaria, and diabetes, we have many pharmaceuticals that were originally inspired or provided by plants.
So we're not talking about things that are limited to herbal medicines that you might buy in a alternative remedy shop. We're talking about things that you'd get in a regular pharmacy that would be prescribed on the NHS, for example.
Precisely. I mean, up until around sort of the early 19th century, most people were using plants in the form of herbal medicines. So these contain mixtures of many different plant compounds. But then in the early 19th century, morphine was first isolated from the opium poppy. And this completely revolutionized how
people used plants as medicine. Because for the first time, we were, or humans were, isolating single chemicals from plants and then developing these as a medicine. So this is really the concept of the single active ingredient or the pharmaceutical that we are familiar with in modern medicine today,
Opium and its derivatives are still used in modern medicine.
Absolutely. I mean, opium is a source of not only morphine, but another analgesic, which was also discovered in the 1800s, which is codeine. And both of these are currently in clinical use. And we still rely on the plant to obtain these alkaloids. Because as humans, we can't synthesize them easily from scratch in the laboratory. But morphine isn't just used itself as an analgesic. It's actually inspired the
development of many other medicines. So this includes other analgesic medicines to help with pain, but also for other types of drugs, which are used for conditions such as coughs, addiction, and also Parkinson's disease. But opium also contains a completely different type of alkaloid chemical called Papaverine. Now this has very different properties. So one of its effects is
that it can dilate blood vessels. So this compound was used to inspire the design of a drug called Verapamil, which is now in clinical use for certain heart conditions. So the opium poppy has been very important in discovering medicines, which we still find useful today. Plants are actually
brilliant chemists. The story of aspirin is actually a very interesting story as a medicine, because it's discovery began in the mid 1700s when the bark of the willow tree was tested in people, and it seemed to be useful to reduce fevers. But it wasn't until the next century that it was discovered that the willow bark contains a certain type of chemicals called salicylates. And these were found
to be the active ingredients of the willow bark. And they were the inspiration for the developments of the drug aspirin. But then it wasn't for another 80 years or more, that scientists actually uncovered its mode of action. So aspirin in the 1970s was found to inhibit the synthesis of some inflammatory substances in the body called prostaglandins. But
its story doesn't end there. So even much later still, aspirin was found to have another completely new role in medicine. It was found to inhibit the aggregation of platelets in the blood. So as a result, aspirin became used more widely as a medicine to help reduce the risk of blood clots in people that could be at risk
of certain heart conditions. So from the 1700s to the 1990s, we've still been making discoveries about a widely used drug, originally inspired by a plant.
So it isn't just about harnessing a chemical that instantly has a therapeutic effect. It can be sometimes just using it as a roadmap for inspiration. But the compounds found in plants can be useful as an ingredient in which to create drugs after.
Absolutely. Yeah. Much of the research we've been doing in recent years is looking at members of the mint family, so the lamiaceae. So these are common herbs, which are often used as part of our diet for flavoring food, such as sage, rosemary, lemon balm, and mint. And we've
found some very interesting properties associated with these. We're really scrutinizing their chemistry to find out which specific chemicals occur in them and how they might have potential effects that could be useful to our health. Particularly, if used as part of our diet.
It's thought that up to 50% of medicinal plant species will be extinct by the end of the century.
So it's absolutely critical that we can protect biodiversity. There is now a shift to looking at plants, to use them to inspire us, to discover new medicines rather than exploit them.
It's so easy to dismiss plant- based medicines as merely interesting historical anecdotes, a relic from another time. Yet 80% of the human population still relies on compounds found in plants as their primary form of healthcare. With at least half of all of the most commonly prescribed pharmaceuticals being originally derived from natural sources, unbeknownst to us, this includes a large chunk of the stuff in our own medicine
cabinets. From local indigenous populations to international world- shaping cures, plants have been essential to human health since the dawn of humanity. And the reality is even today, we're still just beginning to scratch the surface of their potential. Thanks to breakthroughs in modern technology, we're able to travel further and learn more about how we can demystify these properties
to make better lives for all. And none of this would have been possible without working alongside the people who live near and use those plants, being so generous with their knowledge. These communities and the information they share, can
be absolutely vital to scientific discovery. Understanding the potential applications of plants from people who've been using them for 100s, if not 1000s of years has repeatedly proven to lead to game changing medical discoveries. And there is so much
more to learn. To me, it's quite incredible to think how much of our learning in this area has taken place in the last few hundred years, a blink in the eye, in the history of our species, making use of the collection, knowledge and tools that we expand upon
every day. Now that this information is more available than ever, our next challenge is how to create a sustainable and respectful relationship between biodiversity and human progress to future proof our planet for generations to come. The journey really has only just begun. Next time on Unearthed from Kew.
These leaf cutting ants, it'll make them climb towards the light whilst the fungus finishes off the insides. And then once it's finished eating it, it bursts out and produces this little fruiting body. It's drawn out and horrible.
When did you last come in contact with mold, fungus, and the like? Chances are you're doing it right now. And your life's a lot better, thanks to this remarkable kingdom. Next time I'll be delving into the forgotten world of fungi, and finding out how little we still know about one of the most important and mysterious elements of
life on earth. Plus, I'll hear about the surprising links between psychedelic mushrooms and our mental health.
About 15 years ago, we decided it was time to explore the brain science of magic mushrooms. And I think my claim to fame that I've probably given more different kinds of drugs to human beings than anyone alive, but the good news is they're all still alive too.
Make sure you don't miss it by subscribing on your podcast app now. You can share this episode with a hashtag # KewUnearthed and follow us at Kew Gardens on social media. Join in the conversation with the hashtag # KewUnearthed. I am James Wong. Thanks for listening.