Instant Genius - Why the new era of life-saving drugs starts with plants

Episode Date: December 15, 2025

Chances are that if you open your bathroom cabinet, many of the medicines you find there were first discovered by studying the chemical processes of the plants that grow all around us. But with 450,000 plant species existing in the world, the truth is that we’re only just scratching the surface of this almost limitless resource. In this episode, we’re joined by Prof Anne Osbourn, a group leader in biosynthesis research based at the John Innes Centre, Norwich, and co-founder of drug discovery platform HotHouse Therapeutics. She tells us about the long history we humans have of making use of the medicinal properties found in plants, how technological developments over the last several decades have enabled us to identify the genes and naturally occurring processes in plants that we can harness to produce life-saving drugs, and how artificial intelligence shows great promise in our search for new, innovative medicines. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Chances are that if you open your bathroom cabinet, many of the medicines you find there were first discovered by studying the chemical processes of the plants that grow all around us. But with 450,000 plant species existing in the world, the truth is we're only just scratching the surface of this almost limitless resource. In this episode, we're joined by Professor Anne Osborne, a group leader in biosynthesis research based at the John Inez Centre in Norwich, and co-founder of Drug Discovery Platform, Hot House therapeutics. She tells us about the long history we humans have of making use of the medicinal properties found in plants, how technological developments over the last several decades have

enabled us to identify the genes and naturally occurring processes in plants that we can harness to produce life-saving drugs, and how artificial intelligence shows great promise in our search for new innovative medicines. Welcome to the podcast. Thanks so much for joining us. Thank you. It's very good to be here. So today we're talking all about plant engineering. So first off, I think we need to get the big question out of the way. What exactly do we mean by plant engineering? You know, it's not just growing things in our greenhouse, is it? Well, I think in the area that I work in, there are multiple ways of engineering plants for different purposes, but we're interested in the ability of plants collectively, the whole

of the plant kingdom, to make all sorts of different types of chemicals. And these are the kind of chemicals that are associated with the scents, the colours, the flavours, and drugs or drug leads. So, for example, Chinese traditional medicine for 4,000 years has been using plants and the chemicals that they produce to treat human ailments. So we're interested in understanding the chemical engineering capability of the plant kingdom and harnessing it and putting that information to work inside a sort of surrogate plant host so that we can make designer chemicals on demand. Yeah, so we'll get into some of the technical details in a bit, but you mentioned that, so native cultures have been using plants medicinally for, I mean, as far as anyone can

remember. And even now, like when it comes to, like you say drugs and medicines, for example, something like half of the drugs that were currently in use originated in plants, is that right? So around half of the drugs that are in current use are either natural products or natural product inspired. And natural products are, you might think of them as exotic chemicals that are made by plants and also by microbes by bacteria and fungi. So they are molecules that are biosynthesised by living organisms, which distinguishes them from the kinds of chemicals that humans make in the laboratory. The reason why they're such a rich source of drugs is because these molecules have been honed by evolution to do useful things in the environment to help microbes and plants survive.

And so they've been honed to interact with biological targets and processes and pathways. And that means there are a very rich source of bioactive molecules. Yeah, so before we get into the meat of it, can you give us a few common examples that we might all have in our bathroom cabinets, for example, that have been made from plants? Well, obviously, I mean, aspirin is inspired by a compound made by the willow tree, salicylic acid. Aspirin is a very simple molecule, and it's actually synthesized commercially using chemistry. But then other very important drugs such as morphine, which is made by poppy, that's a very complicated molecule, and that still can't be synthesized in the laboratory because humans aren't as good at making molecules as living organisms are.

So we've mentioned there that sort of the origin in native cultures, but when did we really start analysing the chemical compositions of plants, I guess, to take this process a step or two further? So in the early 1900s, advances in chemistry, particularly companies like Merck in Germany, revolutionised drug development by enabling the purification of chemicals from plants. So there was a big revolution in chemistry there that paved the way for the modern pharmaceutical industry. And that's when compounds were purified. So they became pure drugs instead of extracts

from plants, which of course is what is commonly used in traditional medicine. So as I understand it, we're sort of only just scratching the surface of this vast resource. You know, what can we say about that? You know, how many plants have we identified that are useful for these purposes? Well, there are lots of different plants that have been identified in different cultures, including the British, the herbal medicines. But I suppose, although we know collectively that plants make around a million compounds, shall we say, that's only the tip of the iceberg, because those are only the ones that

we've discovered. And so we know that as we learn more about plant genome sequences, which contain the instruction manual needed to make the chemistry, we're realizing that around 20% of that information is likely to be dedicated to making chemicals, most of which we haven't yet discovered. So before we get into the sort of real science then, how do we go about finding these plants in the first place? Well, there is the history of traditional use, but increasingly we're able to discover entirely new molecules by reading the genomes of plants.

But I could give you a recent example of a molecule which has a very interesting history. It's called QS21, and it's produced by a tree that grows in Chile, in the central part of Chile. And this molecule is produced in the bark of the tree. So the tree historically, it's called the soap bark tree, and its Latin name is Kiaha Sapinaria. And it's called soap bark, because the bark has been a source of soap and shampoo used for hundreds of years traditionally. And that's what it was known as. It became a commodity during the Spanish occupation of Chile. The bark was exported to Europe, where it was also used as a source of soap and shampoo.

And then somehow in the early 1900s, the veterinary researchers realized that this extract from the bark was actually very good at promoting an immune response in animals, along with the vaccine. So it boosted the immune response. And the molecule responsible for that was purified from the bark extract. and found to be this QS-21. So then the soap bark tree went from being a source of soap and shampoo to being a hugely valued source of this very important molecule QS-21, which was approved for use in human vaccines in 2017,

and is now worth between $100,000 and $400,000 a gram. Wow. Batonone. So you mentioned their genome, genetics. So genome sequencing has been a huge revelation. over the last quite a few years now in many areas of scientific research. So what role does that play in regard to this concept of plant engineering? So it's very important. So obviously the human genome was something we've known about the human genome for a long time.

A lot of money went into sequencing the first human genome, which was the equivalent of trying to put somebody on the moon. It was a huge ambition then. Since then, the genomes have been. many organisms have been sequenced. Initially, there was a lot of focus on microbes because they have small genomes and they're an important source of antibiotics and so on. And plants were a little bit behind because plants have bigger genomes, they're more complicated. But as the technology has advanced and things have become cheaper, plant genomes are now being sequenced on a daily basis.

The first plant genome sequence was released in the year 2000. We now have genome sequence for around 1,800 plant species in the public domain. There are around 450,000 species of higher plant on the planet. So there's still a big gap in terms of genomes we haven't yet read, if you like, but we've already learnt from those first 1800 that there is a huge amount of information that enables us to understand and harness the chemical biosynthetic pathways from plants. So you mentioned that plant genomes are relatively large. So once we've got the genome sequenced, you know, what do we do then?

You know, how do we go about identifying genes of specific interest to us, you know, for useful purposes? Well, that's a very good question. One of the plant species we've worked on is oat, as in the cereal crop, and we worked on a simple version of that which had a simplified genome. But the size of that genome was bigger than the human genome. It was four gigabases. But importantly, a lot of the DNA that contributes to that size is repetitive sequence that does not actually encode as far as we know. It doesn't encode proteins and so on.

So although the genomes of plants are much bigger than those of microbes, in general, your average plant will have around 35,000 genes in its genome. It's just that in some genomes they're spread out more, there's more intervening DNA. So you're looking at, let's say, 35,000 genes and you might want to find the 15 or 20 that are required for the multi-step process involved in making these complex molecules. And that's where you need a lot of computational capability, bioinformatics, you need to be able to read through these genomes, spot where the genes are, which are actually doing the business bit. and then you need to be able to, from your 35,000 genes, use a set of complementary computational approaches to narrow that down to say 50, and then you can do some experiments to get to the actual 15 or 20 that are doing the necessary.

Yeah, so do we use things like artificial intelligence and machine learning to help us with this process? So artificial intelligence is increasingly, and machine learning are increasingly being applied to streamline the process of reading plant genomes and finding out where genes are. Plants have lagged behind other organisms in this regard. They are a bit of a Cinderella,

but because most of the effort is going into human genome sequences, animals and microbes, but that's improving now. And so there are many steps at which AI can help, including spotting the genes in the first place, making sure that the reading of the genes is high-quoise, But then working out what those genes do is still a big challenge. So for animals, we know that many of the genes are conserved across animal species.

Whereas with plants, because they have evolved the ability to make this vast array of chemistry, their genes have just gone off and diverged and done different things. So many of the genes in plants do not share similarity with genes in humans and other animals. So it's a different challenge in that we have to, develop ways of understanding and decoding that explosion of diversity that's happened in plant genomes. And that's a big opportunity, but also a big challenge for AI. And one of the big challenges there is there, there's sort of some rudimentary steps. The plant genome sequences that are already available publicly are available in various formats. Some of them are very high quality. Some of them

are not. Some of them have the positions of the genes noted on them, a bit like a map, and some of them don't. And so to set up a system where you can take currently the 1800 or so genomes that are out there and streamline them and feed them into a pipeline so that all of those little niggles are ironed out, that's a big step. But we have developed a very good way of doing that. And so now we can make collections of hundreds of thousands of genes that we think belong to a particular family of enzymes that do something to do with chemistry. Ah, yeah, so having said that, once we've identified the genes of interest, what's the next step then to construct, if that's the right word,

useful chemical compounds based on that knowledge? So there are plenty of plant genome sequences out there. I've already said we can debunk them in terms of setting up a pipeline to get these really high-quality curated sets of tens of thousands, of thousands of genes, but then we need to work out what those genes do. Often, research groups around the world who work on understanding how plants make chemicals will take the genes from the plant and they'll put them into a little workhorse like Baker's yeast, which is commonly used to express genes of plant origin and of other origin.

And so you can take the genes from plants and put them into baker's yeast where, if you're lucky they'll make the chemistry. The problem is that, is that although Baker's yeast is widely used, certainly by industry, it isn't a plant, and it's missing lots of the things that plants need in order to make the chemistry properly. So we have started using, well, a long time ago now, we started using a system developed here at the John Innis Centre, where my lab is based, that involves using a plant system as a heterologous host, a surrogate host, to do this. And what we use is a wild relative of tobacco called Nicotiana Benthamiana that happens to be particularly amenable to this process. So we grow these plants in our glasshouses.

We have hundreds of them growing every week. We take the genes that we want to express and we put them into a little bug called agro-bacterium. And agro-bacterium is actually used for making stable transgenic plant lines, which is not what we're doing here. But what it does is it will take the DNA that you've introduced into it and transfer that inside the plant's cell. And then the plant does all the work. The plant will express the gene and then make the chemistry. And the process is really quick so we can take our agro-bacterium containing the gene, squirt it into the leaf of this wild relative of tobacco, which has big juicy green leaves.

And then five days later we can grind the leaves up and see what we've made. So it's very, very quick. So we analyse the leaf extract using big machines that go beep, that detect metabolites in various ways. They can detect the chemistry. And so we can go through multiple cycles of this very, very quickly to test combinations of genes and build up pathways. And that's what we did for this QS21 pathway from the Chilean tree.

We sequenced the genome, found the 20 genes that we needed to make the chemical, and we assembled them using this transient, rapid plant expression system You said this place was steps from the water We just haven't found

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So this bug that I mentioned, to Agro-Bacterium, is actually, it's a naturally occurring bacterium that in the wild causes crown-gull disease of plants, so people who are keen horticulturalists will know about crown gall disease. And the way it does that naturally is very cunning. It has a little piece of DNA called the T.I. Plasmid. That doesn't really matter. Once Agro-Bacterium infects its plant host,

that little bit of DNA is transferred naturally into the plant cell, where the bacteria is then getting its genes to be expressed by the plant, which is a clever trick. What plant scientists have done is to take this naturally occurring agrobacterium strain and disable it so it doesn't cause crown gall disease, but it will still do this process of transferring genes into the plant. So we swap out the genes it would naturally transfer, which would be its virulence genes, and we put in the genes to make chemistry,

and then the agro-bacterium very obligingly shuttles those genes into the plant cell, and the plant cell doesn't know the difference, so it just treats those genes as if it were its own. So let's have a look at some of the chemicals that we can produce, the useful chemicals we can produce through this process. So I'd like to start really with vaccines, because I think we're all really keenly aware these days of the effective need for vaccines in the wake of the COVID pandemic. So is it possible to create effective vaccines using this process? There are two things there. So vaccines are disabled pathogens or parts of pathogens, parts of disease-causing agents that are used to

inject into an animal or a human to trigger an immune response. That's what a vaccine is. The molecules that we're working with are not vaccines, but they boost the activity of vaccines. They're called adjuvants, vaccine adjuvants. So they are mixed with the vaccine and injected into the animal or human, humans are animals anyway, to get a better immune response. So this QS21 molecule was the first natural product to be used in a human vaccine and it was used in the GSK-Shingrix vaccine which was approved in 2017. Since then it's been included in several other vaccines that are now in commercial use.

it's in a number of other vaccines that are in the pipeline. So QS21, as I said, I told you the story about how it was discovered because it was in the bark of the soap bark tree, which was being used as a soap. Somebody randomly stuck some of that bark extract into an animal in France, a veterinary scientist tested it to see if it would boost the immune response. So he was looking at a forgotten which, but a particular human pathogen. This was in the 1920s. It was a guy called Gaston Ramon and he is known to be the person who has been the most nominated for a Nobel Prize without getting one. Oh, no.

And in 1920, he was studying vaccines and he got the idea that if you got an aggressive inflammatory response when you immunised an animal, you got a better immune response. So that led him to start sticking random things into his vaccines, which included breadcrumbs and tapioca. Somewhere, and there's a gap in the literature, I've been trying to try. trace this. Somewhere over the following 10 or 20 years, somebody expanded that study to include this bark extract. But Gaston Romain was the person who invented the term adjuvant to refer to vaccine adjuvants. So QS21, although it's now used widely, is a good immunostimulant, but it's

quite toxic to humans. It has to be carefully formulated. And there's concern about the sustainability of the supply chain. Because the demand for it is growing, it's extracted from the bark of wild trees that grow in Chile. The other important thing is that the tree makes around 100 structurally related molecules, including QS21. Some of those molecules are simpler than QS21 and they're very good immunostimulants and they're less toxic to humans, but they're present in very small amounts in the bark extract. So now we've sequenced the genome of the tree and we've elucidated the QS21 pathway, and we have a kind of SATNAV to look at the whole genome of the tree, to look at the instruction manual, and we've been working out how to access these other

structural variants so that we can make, for example, a simpler one called QS7, which we've already made. And this is very exciting because it's been very difficult so far to try to understand what the features of QS21 are that make it such a good adjuvant. But now we can engineer different versions of that. And those can go into structure activity studies where they can be evaluated to see how effective they are as adjuvants and also to look at their toxicity to humans. And that's all all done in the lab without the need to sort of go out and collect the bark from these trees.

Is that right? That's right. So what we've done is the first example of making free from tree QS21. And we did this using our transient plant expression system. We reconstituted the whole pathway in our transient plant expression system, albeit at low levels. We've also collaborated with the group of Jay Keesling at UC Berkeley in California, University of California, Berkeley. And Jay's group took the genes that we'd characterized and the intermediates that we purified and used. use those to support his group in reconstituting the pathway in baker's yeast, which, as I've said, baker's yeast is not ideal for making plant chemicals,

because it's missing many of the bits. So we needed 20 genes to express the QS21 pathway in our plant host. Jay needed 38, which he scabbaged from across, from different organisms, and he also had to do a lot of engineering to his Baker's yeast chassis. and he got a very low level of QF21 as well. So it'll be interested to see going forwards, because we haven't optimized any of this yet, there's plenty of scope for optimizing

and, as I say, for mixing and matching genes to make different flavours of these molecules with the idea of being able to produce them without stripping the bark off the tree, insufficient quantities, and tailoring them for different types of vaccine. So the shingles vaccine is obviously for the older day,

demographic, whereas QS21 is also in a malaria vaccine, which is targeted at children in malaria-stricken areas of the world. And there's plenty of scope for trying to find the best adjuvants to work with the best vaccines for different demographics. That's a whole new area that hasn't really been tackled yet. So how about things like antibiotics? So I think it's been something like 40 years, I think, since we discovered a new class of antibiotics. Antibiotic resistance is becoming a huge issue worldwide, and not only in humans, in livestock and things like this. So can this plant engineering process perhaps help combat this problem? It could well do. That's something we've talked about.

The antibiotics, most of the antibiotics in current use are from microbes. My colleagues here work on bacteria such as streptomyces, which is where streptomycin comes from. It's been a lot of work in microbes. plants also make chemicals that are antimicrobial because they need to protect themselves against invading microbes for one thing. And so I think that that's a whole new area that needs more attention. We've certainly uncovered new pathways from plants that make molecules that have antimicrobial activity. And it would be very interesting to know how many types of molecules there are out there and how they compare with microbial molecules. Yeah, so we've been talking about

medicines so far. But how about other promising areas that plant engineering could help us with? Thinking about things like food sustainability, for example, you know, can we make more resistant crops, faster growing crops, more nutritious crops, things like that, etc.? Yeah, and again, that's a whole, there is lots of activity in all of those spaces. So my own area is focused on understanding how plants make chemicals for therapeutic purposes. But the general principles of understanding how plants make chemicals are the same, whether it's a chemical that is an anthocyanin that's beneficial for health. I have a colleague here who works on the purple pigments that plants make and on engineering or gene editing plants to make them more nutritious. And then the whole business of protecting, developing the crops of the future that are more nutritious and more resilient to biotic and day biotic stress and to climate change.

understanding how their chemical repertoire helps them to survive and combat these various stresses, and optimizing those processes is another area. One of the things that we have been working on is molecules that are produced by the Neem tree, which grows in India and other parts of Asia, and Neem makes molecules called liminoids, which are anti-insect compounds, but they are friendly to bees. and there's a lot of interest in liminoids as the insect deterrence of the future. So we've been working with the neem tree and its relatives to understand how that tree makes those molecules.

And again, we've elucidated a long part of the pathway, and we've reconstituted the pathway in our transient plant expression system. And we've been developing ways of working with our insectry here so that we can test our compounds to see what they're doing to insects. Yeah, so we've heard quite a lot there, and it's quite clear that this area of research is very promising. What would you like to see in the future of this area in the next, let's say, five, ten years? What are some sort of headline things that we'd like to tackle? So a lot of the work we've been doing so far has been to do with reading genome sequences and understanding particular pathways for QS21 or for the liminoids, or there are many examples of pathways that other people have worked on.

However, now we're at a point where we have 1,800 or so plant genome sequences, and there are large-scale genome sequencing initiatives going on around the world to sequence every species on the planet. And we have 450,000 or so higher plant species. 20% of the genes in plant genomes are doing chemistry, but we don't yet know what they do. And if you multiply that by the 450,000 plant species, gives you something like 3.5 billion genes that we need to harness. We need to understand and

harness. So what we're doing now is moving away from, we're still interested in individual pathways of interest, but the bigger picture now is to look at all of that metadata, to step back and look across genomes and to think, how can we use AI and machine learning to extract and distill all of that information? And one of the challenges there is that although AI and machine learning can do great things. They can't if they don't have the experimental database. If they don't have the experimental data, you can't train them. And we need to go a lot more automated, a lot more high throughput, a lot more robotics. It's a different way of doing science. It's not just, you know, one PhD student in a lab cloning one gene in three years. This is now a huge opportunity,

but we're going to have to start thinking differently. It's cross-disciplinary. My group already has computational people, chemists, medicinal chemists, as well as biologists, molecular biologists, microbiologists. So great opportunity for huge team stuff. And it'll be really exciting to go through these cycles with AI to predict and then test and see how much hallucinating goes on in that process. But ultimately, if we can garner the whole of the instruction manual from the plant kingdom and feed that into our, you can think of it as a, a cycle that will get more and more powerful, where we read, we test, we learn, we go round and round. In parallel, we can use the growing body of data for chemicals. There are big databases

out there that report on the activities of tens of thousands of chemicals in particular assays for disease-related indications. So you can use machine learning to learn the features of molecules that make them good at a particular thing. So if you can do that, you can use machine learning to guide what you want to make, and then you get your platform to design and make it. So you end up with an increasingly powerful platform that can make designer molecules targeted for all sorts of needs, human diseases, things for which there is no cure at present,

things that are better, and so on. So it's a huge vision, but it's very exciting as well. Thank you for listening to this episode of Instant Genius, brought to you from the team behind BBC Science Focus. That was Professor Anne Osborne. If you liked what you just heard, then please do consider subscribing to Instant Genius on your preferred podcast platform.

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