Chapter 13: Fungicides: Several Generations and More Needed

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Welcome to the Deep Dive.

Today we're embarking on a really crucial journey into a hidden battleground of agriculture, the relentless fight against plant diseases, specifically those caused by fungi.

We're taking a deep dive into the fascinating world of fungicides and we're drawing our insights today from the Fifth Kingdom, Fourth Edition by Bryce Kendrick.

Our mission really is to unpack the evolution of these vital chemicals, you know, from their accidental discovery way back when to today's sophisticated targeted solutions and also understand the ongoing challenges, the ingenious strategies we use to keep our food supply safe and abundant.

Think of this as your essential guide to understanding these silent crops.

Yeah, it's truly fascinating how fundamentally important this topic is.

It ties directly into, well, the foundations of human civilization.

Agriculture allowed populations to explode, right?

But it also created the absolute perfect conditions for plant diseases.

When we grow lots of the same plant close together, what we call a monoculture, it's basically an open invitation for anything that feeds on that plant to just thrive.

Today, we're focusing specifically on problems caused by true fungi, the Umicota, and also a group often mistaken for them, the pseudofungi or Umicota.

Keeping those distinct is actually helpful.

It really is.

And for millennia, humans had absolutely no idea what caused most plant diseases.

Seriously, no clue.

They blamed crop destruction on everything from, like, mysterious humors to a fluvia of the earth.

It really shows you how far scientific understanding has come.

Absolutely.

Just think about the devastating Irish potato crop destruction back in the 1840s.

That was caused by Phytophora infestans, which is an Umicota.

This disease just went completely unchecked, leading to terrible human consequences simply because nobody understood the true biological cause.

It's kind of astonishing that the first praxil fungicide wasn't even devised for another 40 years after that.

Wow, 40 years.

And even with all our scientific advances today, here's a all crop losses today are still due to fungal diseases.

That costs billions every year.

Now, while some pathogenic fungi, like a Puchinia graminis that's the one causing rust, can be controlled by breeding resistant plant varieties, a lot of our commercial crops remain highly susceptible.

Take apple scab, for instance, caused by venturia and equalis.

The conditions for infection are just so common that unprotected orchards might yield basically no saleable fruit at all.

Zero.

So in situations like that, fungicides become absolutely necessary.

Sometimes needing, you know, six to 15 sprays per year.

This really sets the stage for our deep dive into the chemical solutions.

Okay, let's unpack this journey then.

Starting back in the 1880s with what we call the first generation of fungicides, the inorganic protectants.

Where did this begin?

Well, our story really kicks off in the famous vineyards of Bordeaux, France.

These vineyards were being absolutely ravaged by downy mildew caused by Plasmo para Viticola.

Professor Millardet, he was walking through a vineyard and noticed something curious.

The vines right next to the paths looked much healthier.

He found out it was custom to spatter them with this obvious poisonous looking stuff, vertegris, basically copper acipate, just to stop people from stealing the grapes.

Millardet, knowing a bit about fungal habits, started mixing things up.

He realized he could poison the fungus when it was most vulnerable, right when its delicate spores, mitosporange or releasing zoospores, landed on wet plant surfaces.

Ah, clever.

And this insight led to the famous Bordeaux mixture, right?

That blend of copper sulfate and calcium hydroxide, or quicklime.

Precisely.

Bordeaux mixture, and pretty much all fungicides before about 1960, are what we call protectants.

This means they're toxic to fungi, sure, but only if they intercept them outside the plant.

They form a kind of protective coating.

Think of it like armor for a plant.

Once the fungus gets inside its host, these chemicals just can't reach it anymore.

Okay, so what were the practical challenges then?

You can imagine, right, if the plant isn't totally coated, or if like new leaves pop out.

The fungus can sneak in, exactly.

And rain could wash it off, meaning you had to spray again and again.

Sounds like a constant battle.

It really was.

And this constant reapplication, plus the fact these were inorganic compounds, led to other problems too.

They could be phytotoxic, meaning they could actually damage the plant itself.

And long -term use, like Bordeaux mixture on grapevines for years,

resulted in copper building up in the soil.

Sometimes to pretty alarming levels, like 130 parts per million.

And were there other early options besides copper?

Yeah, there was sulfur.

It's actually still used for things like powdery mildews today.

But even sulfur had downsides.

It could scorch leaves, or stunt the plant's growth, and then there was mercuris chloride.

Mercury.

That sounds potent.

Oh, it was.

An excellent spectrum fungicide.

Because heavy metals generally denature a wide range of enzymes.

They just mess up their structure and function.

However, the toxicity to animals was severe.

The LD50 to rats, that's the dose that kills half the exposed animals, was shockingly low, just one to five milligrams per kilogram.

And even low long -term exposure could cause severe brain damage, like we saw with Minamata disease.

It was crystal clear we needed something far, far better.

Something that didn't poison everything else.

Right.

That challenge really pushed scientists, didn't it?

And this is where it gets, well, really interesting, as they started exploring organic compounds around the 1930s, moving us into the second generation of fungicides.

Yeah, this shift was a critical turning point.

The organomercurials were among the first of this new wave.

Now, they still had mercury, but they were designed to be less poisonous to animals, while keeping that strong, fudgy toxicity.

Since spraying them widely was still too risky, they found a niche mostly as seed dressing.

Very successful at controlling lots of seed -borne and soil -borne diseases like rots and damping off, though even these have been largely replaced now.

Okay, so trying to make them safer, more targeted.

What else emerged in the second generation?

Well, a really crucial family were the DTL carbamates, which came along in the 1930s.

They were organic protectants known for having very low phototoxicity, much gentler on the plants.

You have types like therum, still used as a seed treatment, and the ethylene -bis -tetegocarbamates, the EBDCs, like mannab and mancosyab, these made a huge difference for potato yields, because they were much less damaging than the old copper compounds.

That sounds like a massive improvement for farmers, but I'm sensing a butt coming.

Always a new challenge, right?

You're right, there often is.

While they were effective, the EBDCs,

they break down to form something called ethylene thuria, and that's a known carcinogen.

It also

malformed offspring in rats, even at low doses.

So you need special precautions, especially with cooking, to avoid food contamination.

It's a trade -off.

Okay, another important group you mentioned from this era were the thalamides.

Captain was the big one there.

Yeah, captain.

Registered in 1951, had a really versatile foliar spray and seed dressing.

People liked it because it has a very short half -life in the environment, and importantly, pretty low mammalian toxicity.

The LD50 is way up at 9 ,000 mjkg, much safer.

What makes captain interesting in terms of how it works?

Captain is fascinating because, a bit like the heavy metals, it acts on multiple sites within the target fungi.

It disrupts lots of different cellular processes at once.

This multi -site action makes it much harder for resistance to develop quickly.

That's a really key insight that becomes important later on.

It's used widely on fruit crops, apples, peaches, strawberries,

preventing maybe 25 % crop loss.

It's faced some controversy over alleged carcinogenic effects, but studies haven't really proven those claims conclusively, so its use continues carefully because we lack equally good alternatives.

Right, and beyond those, we also saw things like organotins, phenols used as wood preservatives or disinfectants, sometimes killing overwintering fungal stages, like the telomorph of apple scab.

Exactly, and keynotes too, like declone for apple scab and chloranil, which famously brought a huge return to the pea industry in just one year.

So this second generation really shows that shift towards more refined, sometimes safer, but still largely protectant chemical solutions.

Yes, exactly, and this constant pursuit of refinement, always pushing for better efficacy and safety, it led directly to the next major leap.

So what does this mean for the future then?

A huge jump came in the 1960s with the third generation, the systemic fungicides.

What made these such a game changer?

Oh, this was truly revolutionary,

because unlike protectants, which just sit on the surface, systemic fungicides could actually get inside the plant.

They could move within the plant tissues and kill the fungus from the inside out.

The benzimidazoles, like benamol, maybe better known as benalase, were the first truly systemic or eradicate fungicides.

They could tackle infections that had already started.

Wow, how did they manage to move through the plant like that?

What was the mechanism?

Benamol was what we call apoplastic.

That means it mainly traveled upwards, sort of hitching a ride in the plant's water -conducting xylem vessels.

Think of it like the plant's plumbing for water.

It accumulated between the cells, but importantly, it didn't move downwards in the phloem, which transports the sugars, the food.

Ah, okay, so if you applied it near the ground, it could protect the growing tips way up high, but it wouldn't protect the roots down low.

Exactly, that was a limitation of its movement.

But the benefits sound huge.

Stable, relatively non -toxic LD50, over 10 ,000 mgkg, and effective at incredibly low doses.

You said 0 .3 kg per hectare, compared to over 5 kg from a neb.

That's massive.

Huge difference.

Fewer sprays needed, less chemical used overall.

And its mode of action was completely new, too.

It specifically with microtubule assembly and Ascomycetus fungi.

It basically got absorbed into their spindle fibers during cell division and stopped it cold.

Incredibly effective.

It controlled pretty much all major fungal diseases on apples, leading to its widespread adoption by farmers around 1973.

Okay, that sounds almost like a miracle cure.

But given the pattern we've seen so far, I have a feeling there was a catch.

What went wrong?

You are right to be wary.

By 1975, just two years after it became widely used, some key apple pathogens, including Venturia, apple scab, and Penicillium storage rot, had developed complete resistance to binomial.

It just stopped working on them.

Its registration eventually lapsed largely because of this rapid resistance development.

Only two years?

Wow.

Yeah.

It highlighted a critical vulnerability.

The more specific the fungicides target, hitting just one very specific process in the fungus, the easier it potentially is for the fungus to evolve resistance through just a single genetic mutation.

It's this fundamental paradox, a real challenge in this chemical arms race.

So scientists didn't give up, obviously.

They pushed for even more sophisticated systemics.

What came next in this third generation trying to overcome these limitations?

Well, they developed ambimobile systemic fungicides.

These had better movement, potentially reaching new plant growth, not just the parts directly sprayed.

And the amount of mobility varied.

Some could move both up and down in the plant, though that's less common.

Others, like some demethylation inhibitors or DMIs, and the keynote outside of neighbors, QIs, had more limited movement, maybe just moving through the thickness of a leaf.

But even that limited translaminar movement was valuable.

It let the fungicide reach the underside of leaves, which is where many pathogens actually do their damage.

And we also got more selective fungicides, right?

Ones that targeted specific groups of fungi.

That sounds beneficial for, say, preserving helpful microbes in the soil.

Exactly right.

That was a big plus.

Good examples are phosphorus acid fungicides, like Fosatol Al, trade name Alliette, and phenolamides like Mephenoxam, which is Ritomil.

These selectively hit Umicotigenera, like Phytophthora and Pythium, the ones causing those really damaging root rots and downy mildews.

Alliette even had the added bonus of stimulating certain beneficial endomycorrhizal fungi.

A nice side effect.

Okay, and then there are the sterol inhibitors.

How do those fit in?

These are another important family.

They are systemic, though generally non -selective, among the true fungi.

They work by stopping the fungus from making ergosterol.

Ergosterol is a crucial component of fungal cell membranes, sort of like cholesterol in animal cells.

If the fungus can't make ergosterol, its growth is severely limited.

Phenermol is an example.

They're effective against a wide range of Ascomycetes and some Basidiomycetes, and at even lower dosages than binomial.

Phenermol controls apple scab at just 0 .065 kg per hectare.

Really tiny amounts.

Incredible efficiency.

But I'm guessing the resistance theme pops up again here.

They weren't perfect either.

You would be absolutely right.

They often lack long -term residual activity, meaning they don't stick around protecting the plant for very long, so you might need weekly applications.

That's quite demanding for a grower.

And critically, yes, resistance has also developed in certain key pathogens, like powdery mildews.

It's that constant evolutionary pushback from the fungi.

Okay, this brings us to something really fascinating,

and it's an unexpected fourth generation, apparently born from a natural discovery.

This feels like a major plot twist in the story.

It really is quite a story.

In the early 1980s, scientists stumbled upon something remarkable.

A small mushroom and a garrick called Strobilurus It fruits on pinecones of all places.

They found it produced a fungicidal substance, which they named Strobilurin A.

And in the lab, it was incredibly effective against almost all fungi they tested it on.

Wow, a natural wonder.

So why aren't we just, you know, harvesting mushrooms from pinecones to protect our crops?

Seems simple enough.

If only.

The natural Strobilurin molecule, unfortunately, was quite sensitive to light and oxygen and broke down too quickly, making it unstable and pretty ineffective when you actually use it on plants out in the field.

But, and this is amazing, chemists at BASF embarked on this Herculean effort.

Over 13 years, they synthesized and tested over 15 ,000 variations, tweaking that natural molecule.

And their incredible persistence paid off.

It led to the first commercial Strobilurin fungicides hitting the market in 1996.

13 years and 15 ,000 variants.

That's dedication.

So what made these synthetic Strobilurins such a breakthrough, especially after the resistance issues with the third generation?

Well, they kind of combine the best of all worlds.

They have protectant, systemic and erratic activities.

They work by binding very specifically at the Q site on cytochrome B in the fungal mitochondria.

This basically blocks the fungus's energy production, inhibiting mitochondrial respiration at a critical point.

But what was truly unique, a real game changer, was that they were the first synthetic site -specific compounds to provide significant control against pathogens from both major groups of true fungi, the Ascomycota, and the Basidiomycota, and also the Umicota pseudofungi.

Whoa, hold on.

So they hit Ascomycetes, Basidiomycetes and Umicetes.

That's an incredibly broad spectrum for a site -specific chemical.

Exactly.

That broad spectrum activity was unprecedented for this type of fungicide.

Give us an example of how widely these are used now.

Okay.

Well, as oxystrobin sold under trade names like Quadris and Abound was the first one registered, it's now approved for use on pretty much all vegetable crops.

And the list of diseases it tackles is just astonishing.

Calatosporium, leaf blotch, rust, downy mildew, early blight, late blight, black mold, powdery mildew, you name it.

Across onions, corn, cucurbits, leafy greens, potatoes, tomatoes, root crops, it became one of the world's most heavily used fungicides very quickly.

Within just 10 years, it accounted for over 20 % of the entire global fungicide market.

That's incredible market penetration.

Do they offer any benefits beyond just killing the fungi?

They do, actually.

Strobilurins are also marketed for improving crop yield through what's called growth regulatory activity.

They seem to help the plants themselves grow stronger and yield more beyond just disease control.

And their unique mode of action, targeting mitochondrial respiration, has even led to them being explored as experimental antibiotics and anti -cancer agents in completely different fields of research, which is pretty fascinating.

Very cool.

And before we move fully into resistance management, are we seeing any purely biological solutions emerge alongside these sophisticated chemicals?

Yes, absolutely.

That's an important point.

Biological control agents are being developed and used more now.

For example, there's a product called Serenade Garden.

It's a formulation of a specific bacterium, Bacillus subtilis strain, QST 713.

It actively attacks things like powdery mildew and other blights, especially on crops like squash and melons.

It's EPA approved, it's safe for organic gardening, it's non -toxic to plants and beneficial insects like bees, and you can even harvest the crop the same day you spray it.

These are really promising developments offering alternatives or maybe complements to chemical controls.

That does sound promising.

Okay, let's circle back to that recurring theme, resistance.

What's fascinating here is how the challenge seems almost directly linked to how sophisticated these newer fungicides are.

It's like nature just keeps adapting faster, doesn't it?

You've hit the nail on the head.

You probably noticed that resistance really became a serious widespread problem, mainly after we introduced the systemic fungicides.

Now, it's not strictly because they're systemic, but because they tend to be site specific.

They act on one very particular biochemical site or process within the fungus.

Right.

So going back to the earlier ones, the mercury compounds, those broad spectrum multi -site fungicides, they poison so many different enzyme systems at once.

Exactly.

For a fungus to develop resistance to something like that, it would need an almost inconceivable number of genetic changes to happen simultaneously.

It was just incredibly unlikely from an evolutionary standpoint.

But Benamol hitting just that microtubule assembly, well, it became clear pretty fast that with repeated exclusive use, the target fungi could rapidly evolve resistant strains through potentially just one mutation.

And this story, unfortunately, has repeated itself with nearly every new family of systemics we've introduced.

The phenylamides, the carboxymides, the strobilurins we just talked about, the sterol inhibitors.

It really is an arms race.

And you mentioned how quickly it happened with Benamol just two years.

How does that compare to earlier types?

Well, resistance to dodeine, which was an earlier protectant with some erratic connectivity, was first reported in 1969, but that was after about 10 years of exclusive use.

But for Benamol, it was noticed by 1975 after only two years of widespread exclusive repeated use.

That speed up is a huge concern for maintaining the effectiveness of these tools.

So what can we actually do about it?

How do we manage this rapid development of resistance?

What are the strategies now?

We've learned the hard way, really.

We now realize that it's often much better to use mixtures of unrelated fungicides, ones with different modes of action,

or to apply a sequence of different fungicides throughout the growing season, rotate them.

This is core principle of integrated pest management or IPM.

The idea is not to rely solely on one chemical weapon.

If we had done this mixing or alternating strategy right from the start with Benamol, we might have seen far fewer resistance problems or at least delayed them significantly.

It's about not putting all the evolutionary pressure on one single target.

So choosing the right fungicide or the right combination is incredibly complex.

It depends hugely on the specific crop, the specific diseases that are a threat.

Absolutely.

It gets very specific.

For example, a systemic acillinine like mephanoxin is great against an UMI seed like Phytothora infestans potato like blight, but it does absolutely nothing against an ascomyceti like Ultenaria salani potato early blight.

So a farmer growing potatoes might need to use mancosab, maybe, to control the Ultenaria.

And get this, Phytothora itself has now developed resistance to mephanoxam in many areas.

So often, a premixed combination of mephanoxam and mancosab actually works better against leaf blight than either one used alone.

Because of this, many modern systemic fungicides are now only sold premixed with an older, protectant, often multi -site fungicide.

It's a built -in resistance management strategy.

That makes sense.

And how you apply them matters too, right?

It's not just what chemical, but how effectively it gets onto or into the plant.

Very much so.

Many of these systemics are actually almost insoluble in water.

And the plant's outer layer, the cuticle, is designed to keep water out.

So if you apply them just as wettable powders, WP mixed with water, most of the fungicide actually stays outside the plant once the spray dries.

Not very efficient for a systemic.

You get much better uptake if formulated as emulsifiable concentrates, EC, and especially if you add surfactants agents that lower water's surface tension to help the spray spread evenly and humectants, which slow down how quickly the spray droplets dry, giving the chemical more time to penetrate.

These formulation tricks allow for lower dosages to be effective.

And things like advanced sprayers, maybe electrostatically charging the droplets so they're actively drawn to the plant's surface, also boost efficiency.

Seed dressings seem particularly smart for diseases that attack the seeds or young roots.

You're putting the protection right where it's needed first.

They are extremely efficient for that purpose.

In the U .S., over 90 % of corn seed is treated with fungicide.

It's estimated this prevents about a 10 -12 % yield reduction in most years.

That's huge.

And while, yes, seed treatments do put some fungicide in the soil, the newer ones are less persistent, and the total amount applied per hectare is really tiny compared to foliar sprays.

So it's generally not seen as a major environmental issue.

But of course, many crops need more than just seed protection.

Something like cotton often gets seed treatments, plus fungicide applied in the furrow during planting, and later foliar sprays.

Multiple hits.

And what happens if we stopped using these fungicides for certain crops where they're heavily relied upon?

What would the impact be?

Let's take peanut leaf spot caused by Circospora as an example.

There are basically no resistant peanut varieties available.

Crop rotation doesn't really help with leaf diseases like this.

And in the Southeastern U .S., where peanuts are big, the weather conditions are pretty much ideal for infection almost every single day during the growing season.

Without the routine, often biweekly fungicide applications they currently use, estimated yield losses would skyrocket.

They'd go from maybe 2 .5 to 15%, which is manageable, up to a devastating 20 to 75%.

At that level of loss, peanuts would simply become uneconomical to grow commercially in those regions.

Fungicides are literally keeping that industry viable.

Wow.

It really underscores how critical these tools are despite the challenges.

This is clearly a complex, ongoing battle that requires constant vigilance and innovation.

It absolutely is.

And that's why you have organizations like the Fungicide Resistance Action Committee, or AIRFAR.

This is a global industry body.

They categorize all fungicides by their FARC codes.

These codes tell farmers and advisors the mode of action.

Fungicides with the same code have a similar target site and thus a similar risk of cross -resistance developing.

It's like a shared language to guide responsible use and rotation strategies.

Similar groups exist for herbicides, HREC, and insecticides, IRSC.

It's all about managing resistance across the board.

And of course we use other techniques too.

Things like soil sterilization, although some older chemicals like methyl bromide are now banned due to environmental concerns.

We put anti -mold compounds in paints and fabrics.

Even mold inhibitors like calcium propionate in bread to extend shelf life.

It's a constant effort on many fronts.

So wrapping this up, what does this all mean for you, our listener?

We've journeyed through these generations of fungicides, haven't we, from that accidental discovery of Bordeaux mixture in a French vineyard?

Yeah, all the way to the sophisticated broad -spectrum strobalurins, which were inspired by a tiny mushroom found on a pinecone.

We've seen the constant innovation, some really ingenious science, but also that ever -present challenge of fungal evolution and resistance.

It really highlights this continuous arms race, doesn't it?

Yeah.

Between human ingenuity trying to protect our food and nature's incredible adaptability.

We've gone from fairly crude poisons that hit lots of things.

To these highly targeted chemicals designed to disrupt very specific fungal processes.

Exactly.

All while grappling with how quickly resistance can emerge and the absolute need for integrated thoughtful management strategies to make these tools last.

This deep dive, I hope, reveals some of that hidden world of science that really underpins our food security.

It's a delicate balance between making things effective, keeping them safe, and this relentless pursuit of new solutions.

And it definitely leaves us with a question for the future.

What new biological insights, or maybe completely new chemical breakthroughs, might define the next generation of fungicides?

How are we going to continue to adapt and innovate to protect our crops and ensure a sustainable food supply for everyone, especially as the fungi keep evolving right alongside us?

That's a perfect thought to end on.

A huge thank you for joining us on this deep dive into the world of fungicides.

We really hope you feel much more informed about this absolutely critical topic and the incredible efforts involved.

From the deep dive team, thank you for listening.