Talking Trees: Science in the Forest

Cases of malaria have spiked alarmingly owing to COVID restrictions hampering control efforts. The good news, though, is that scientists from New York University have found that they can weaponise a common insecticide and make it twelve times more powerful - just by cooking it in the kitchen microwave, as published in the journal PNAS. The compound, called deltamethrin, is a neurotoxin that sits on surfaces as tiny crystals, and gets inside malaria-carrying mosquitoes through their feet. Heating it up and then allowing it to cool, causes the molecules to rearrange themselves into a different crystal structure that turns out to be much more potent. Phil Sansom heard how from author Bart Kahr…

Bart - If we change the arrangement of molecules in deltamethrin, then the crystals act much more quickly by a factor of 12. That's a factor of speed.

Phil - It was 12 times quicker?

Bart - 12 times quicker when we changed the crystals to the new form.

Phil - Can you give me some context, please? Deltamethrin, is that the compound to use when getting rid of mosquitoes?

Bart - Yes. The leading insecticides that are used today for combating malaria-transmitting mosquitoes are in the so-called class of pyrethroids. These are synthetic compounds that are derived from a compound that's found in chrysanthemum flowers.

Phil - What do people do with it?

Bart - It's incorporated into insecticide-treated bed nets. And the other way that deltamethrin is used is by spraying microcrystals on the interior walls of homes. And that's where the interaction between crystals and the feet of mosquitoes is most consequential.

Phil - And is this something that's working just fine at the moment?

Bart - It's not working just fine at the moment. It's working particularly bad at the moment. And for two reasons, firstly, over the last decade or so, mosquitoes have been turning up, having developed a chemical resistance to deltamethrin. It's also failing right now because Covid interruptions have caused malaria deaths in this very unusual year to skyrocket, because malaria prevention is really a house to house operation.

Phil - It's interesting that you're telling me this. Because you're not an insect person, or a public health person, right? And so what was it that you did?

Bart - We study the chemical and physical properties of crystals made out of molecules. And we discovered a new arrangement or what we call them, polymorphs.

Phil - What does the polymorph look like?

Bart - The old form tended to crystallise as isolated patches with kind of random organisations. Whereas the new form kind of looks like a starburst when it's grown in a thin film. But those two arrangements have different intrinsic energies. And so they will liberate their molecules at different rates when a mosquito should step upon them.

Phil - And how do you get there?

Bart - It's remarkably simple. The way to get from form one to form two is simply to melt form one and then allow the melt to cool and then recrystallise.

Phil - You're kidding. So just by heating and cooling this stuff, you've discovered a new form that's 12 times as effective.

Bart - Exactly. Just by heating and cooling. You can put it on a hot plate. You can put it in a microwave oven. You know, it's like the same temperature as boiling water.

Phil - What's the potential here?

Bart - It could extend the useful life of deltamethrin in the face of chemical resistance. We might be able to introduce enough of the compound, even into resistant mosquitoes, that we overwhelm the rates of the chemical resistance mechanisms.

If you were born before the 1990s the chances are you got a routine BCG vaccination at school. This is used to protect against the bacteria that cause tuberculosis or TB. But recently scientists have spotted a pattern connecting countries with BCG vaccination programmes that repeatedly vaccinate people throughout life and lower rates of Covid-19, suggesting that BCG vaccines, especially in older people, might be protective against the complications of catching the new coronavirus. If that's true, while we wait for a covid vaccine, perhaps we could use the BCG to protect people instead? On the other hand, it could just be a spurious association, and that's what a large trial looking at healthcare workers across several countries is now setting out to discover. Chris Smith spoke with John Campbell, who is at the University of Exeter…

John: These papers that have come out over the last few months have been very important. There's now three of them, at least, that have looked at whether BCG is associated with COVID rates. And in fact, it does look as though there is an association with countries who have high BCG coverage tending to have lower problems with COVID. There is evidence that BCG may have important effects on the immune system acting as a sort of booster to the immune system generally.

Chris - It's not just the simple fact that if you have a country that's rich enough to have a vaccination program, and you compare that with a poor country that doesn't have a vaccination program, you're merely reflecting the richness of the country and its ability to cope with any kind of pressure, and it's not the BCG that's doing it per se?

John - Absolutely. And that's one of the confounding factors that have to be considered in these types of studies. And that's really the reason that the studies that are going to give a definitive answer are going to be based on individual large randomized trials. And that of course is what we are doing. We in the UK are part of a large international research effort led from Melbourne in Australia. And what we are doing is testing BCG compared to a dummy vaccination in 10,000 healthcare workers and following them up for a whole year. And what we're looking at is whether BCG might stop people getting COVID or if they do get COVID, whether it might result in reduced severity of the disease.

Chris - And you'd anticipate that the reason that older people appear to be more vulnerable when they catch COVID, at least one factor might be that any immunity they may have had to BCG administered previously has now worn off with age and therefore they become more susceptible?

John - Yeah. And that's an important observation because a number of countries still have repeat programs of vaccination using BCG. So there's at least 16 countries listed by the WHO, but many people will probably have waning immunity. So what we're doing can probably thought of as a sort of general booster to the immune system

Chris - Is your trial not then going for the wrong group of people because by looking at healthy fit hale and hearty healthcare workers, are we possibly missing a trick? Should you not be going in and hitting older people who are at higher risk because then the effect or impact if there is one would be easier to spot, it would be magnified?

John - There's a strong argument for giving it to older people that is certainly true, but healthcare workers are at the sharp end and we felt that, you know, where we can do something to protect healthcare systems and healthcare workers - that's an important group. And in the UK in particular, we are focusing not just on healthcare workers, but on care home staff who are a particularly vulnerable group of individuals. We think that targeting care home staff and community based healthcare workers is really good because it's very important the healthcare system is also supported.

Chris - It'll be ironic, won't it, if your results show that we've got something already in our medicine chest that we could use against this and we don't need to wait for a vaccine.

John - Yeah. This is the really exciting thing about this study because not only the sort of premise for this study is that the BCG vaccine gives these nonspecific effects, including important effects against viruses - a number of viruses, RSV the respiratory syncytial virus, the flu virus, and some, corona-type viruses, there's good evidence that we may be on to something here - it's been given to 4 billion people. It's safe and it's widely available. It would be fantastic if we found that it could buy us the time whilst the specific vaccines come through.

Chris - And in terms of scale, how much of a difference can BCG make to a person's COVID outcome?

John - The work that has recently been published from Greece within the last couple of months, the so called activate trial, identified that people - older people - who had been given BCG had a really quite remarkable reduction in upper respiratory viral type infections. In fact, it actually reduced by 79% compared to people who had been given a placebo. If we were even remotely near that, it would be absolutely fantastic.

It was once a much bigger number, but these days about 31% of the Earth’s surface is covered by forests, and they’re home to about 3 trillion trees. Trees store carbon; they give out oxygen; and they’re also nice to look at, meaning they enrich the environment in many ways. Adam Murphy spoke to Ángela Cano from the Botanic Gardens in Cambridge about what makes a tree...

Adam - I love trees. I might be a city boy, but put me in a forest, and I'm quite happy to have a good time wandering around, looking up to the canopy. There's nothing quite like being surrounded by trees to make you feel good, but I'm not. There's a pandemic on and I'm stuck inside. So to make myself feel better, I asked Ángela Cano from the Botanic gardens at Cambridge - what is it that makes a tree, a tree?

Ángela - A woody plant that usually has a main trunk, right? This is opposed to, for example, a herbaceous plant that doesn't have wood in its tissues

Adam - That seems pretty straight forward. So how do trees grow differently to make them a tree and not just some weird big vine?

Ángela - Well, all plants grow through a process that is called photosynthesis, where they actually capture the light of the sun and the CO2 from the environment. And through the roots, they also take water from the ground. And with these three elements, they transform them into sugar and oxygen. And the difference between a herbaceous plant and the tree is that the tree can stock that sugar in the trunk and sugars are basically made of carbon. And that's why we think that trees are really good at stocking carbon because their stems basically are made of carbon in a solid state.

Adam - And what is that's going on in those cells to make them so strong?

Ángela - The cells in the stem of a tree, they are, most of them, dead. We call that lignified. So the cells of all plants, they have this wall inside. That's what gives the plant the structure. But then these cells in particular, their walls are full of lignin, which is a compound that is made of carbon and gives the really hard structure of the wood. So if you compare a herbaceous plant that can't really grow tall because they don't have that structure; the tree, because it is able to transform that sugar into really hard lignin it can provide some structure and grow really tall. Because trees, eventually what they are looking for is to reach the light. It's an adaptation to compete against other plants for the light, right.

Adam - How long can trees stick around for, is it a flash in the pan or they're here forever?

Ángela - There are all sorts of ranges here. Because you have what we call pioneer trees that grow very quickly, but then they also die quite fast. And so these are trees that, for example, if you think of a forest and a tree has fallen and then suddenly there is a lot of light in the ground of the forest, you have seeds that are waiting for light to germinate. And so the first seeds that germinate are those that are called pioneers and they can germinate and grow very quickly, but they will die also quite quickly because their wood is not really good quality, right? But then you have these other trees that can grow under less light, that can stand shaded conditions, but they grow slower and these can be really, really old. So there are trees that are thousands of years old. So there is a whole range. The one of the oldest trees that we know about, it's actually a population of trees. The species is called populus tremuloides, and it's found in Utah in the United States, this is what we call in English 'quaking Aspen'.

Adam - There Ángela's talking about Pando, a group of quaking Aspen that is by some measure, the heaviest organism in the world.

Ángela - So these trees can actually form colonies. A single individual has multiple stems that all individually look like a tree, but it's actually, if you look at the roots, they are all connected. It's only one individual that makes clones. And this specific community, if you want, is thought to be 14,000 years old.

The world is currently in the thrall of the COVID pandemic, which has claimed over a million lives so far. But trees aren’t immune to disease outbreaks either, and ash trees are facing their own pandemic. Ash dieback is a lethal fungal disease known as Hymenoscyphus fraxineus that originated in Asia. It first appeared in Europe 30 years ago. UK trees are highly susceptible and this year has been a particularly severe one. Luke Barley, from the National Trust, spoke to Adam Murphy about the disease...

Luke - It's a fungal tree disease. The spores are windborne, they're microscopic and they can travel many miles on the wind. They land on the leaves, and then the fungus establishes itself and grows down through the tree’s cells that we heard about earlier, particularly the hollow tubes at the outer edge of the tree that transport water and nutrients around the tree; and the body of the fungus blocks those cells essentially and kills the tree. In young trees it can kill it really quickly; in older trees it's more progressive, and it kills them slowly but surely from the outside in. The reason our ash are so susceptible is that they haven't co-evolved to deal with the fungus. It's from Asia and it's co-evolved with ash species in Asia; so over there it's more like a leaf blotch, it just discolours the leaves, it's quite a minor ailment because the trees are accustomed to it. But over here, our trees aren't accustomed to it at all, they have no defences against it, no resistance to it. And so it's likely to kill up to 95% of our European ash in Britain.

Adam - How does it spread, and how easily does it flit from one tree to the other?

Luke - It's highly infectious because those spores are windborne. It's been in England since... well, we've known about it since 2012; it was probably here before that. It certainly arrived that year on infected nursery trees from Europe, but it may have arrived on the wind prior to that. And then since then it's been making its way progressively across the UK, and it's now present... certainly here in the National Trust we manage land in England, Wales, and Northern Ireland, and everywhere we look after, ash dieback is now present.

Adam - And what about this year made it so bad? And just how bad was it?

Luke - It's been very bad. We've known it was coming obviously since 2012, so it wasn't a huge surprise in some respects; but like every other infectious disease there's a bell shaped curve to the shape of the infection, and a couple of our landscapes - mainly the chalk and limestone landscapes - the ash in those landscapes seem to be more susceptible. We're already into the exponential phase, but lots of other places weren't, and we seem to have hit the exponential phase everywhere this year. And then that's also been exacerbated by the fact that we had a very, very dry spring, and a very late, very heavy frost; both those things really stress trees out, and that lowers their ability to resist pathogens. So we've seen it really kick off this year absolutely everywhere that we look after. It's been very severe.

Adam - What kind of numbers are we talking about? How many trees?

Luke - On National Trust land it's very hard to quantify, because we don't have a really accurate census of our tree population anywhere. But we know that we're going to need to fell around 40,000 trees this year on National Trust land, just where they could affect public safety if they die - this is by roads or by buildings where people congregate - because as the ash trees die, they become unstable and compose a risk to people. But we think we've got anywhere up to two and a half million ash trees on National Trust land that we won't have to fell; they're just going to die of ash dieback. And it's hard to estimate how many of them are very severely affected this year, but it's quite a high proportion I'm afraid.

Adam - Let's say the worst happens and we lose all those trees; what kind of an impact is that going to have for British wildlife and ecology?

Luke - It's going to have a really big impact. It's going to be very, very sad, frankly. I suppose there's a couple of separate things to tease apart: there's ash in woodlands, and there are some places where it won't have such a catastrophic impact. If ash forms a relatively low proportion of a mixed wood with other species present, then the increased light in that wood as the ash die might actually benefit some species. So that's a thread of hope to hang onto. But where we've got ash dominating entire woodlands we often get a really special ground flora: lots of interesting wildflowers in ash woodlands, because it casts a particularly light shade and its leaves are cycled into the nutrient cycle much more rapidly, so the conditions for wildflowers are great; and that's going to change hugely as whole ash woods die, potentially. So that's going to be really sad. And then the other really sad thing is open grown trees, trees outside woods, places like the Lake District where we've got very significant ash pollards. Pollards are trees that have been caught continually through human history, for firewood and for fodder and for other uses. They're very culturally significant, but they're also home to lots of rare invertebrates that live in the decaying wood in their centre and lichens on their bark. And so we're going to lose all the special species related to open grown ash trees as well. That's before we even get onto ecosystem services. We think that the ash trees on National Trust land might be sequestering anything up to about 700,000 tons of CO2 equivalent; and they provide all kinds of other benefits obviously, whether it's shading or flood alleviation, all those great things that trees do. So the impact is going to be very, very significant.

Adam - What can we do about it? It seems like a massive problem that we should be on top of.

Luke - It's a massive problem. There are subtle things we can do to mitigate some of those impacts for nature in ash woods, by planting other appropriate species, or outside woods by making sure we plant lots of trees. And that really is the long and short of it. In terms of the climate crisis, the crisis in biodiversity, we really, really, really need to establish a lot more trees. And we also need to establish a lot more species, and really make a huge increase in tree cover and make it more resilient to future threats.