S8 E12 - Herbicide Discovery Process

This week on the War Against Weeds Podcast, we have special guests Drs. Cara McCauley and Jason Adams on to chat about the herbicide discovery process. They cover the many things involved in creating new chemistries for farmers to use in the war against weeds!

 

If you want to reach out to either of our guests, you can find them here:

https://www.linkedin.com/in/cara-mccauley/

https://www.linkedin.com/in/jason-adams-6b356322b/

 

Thanks for listening!

Episode Transcript

Joe Ikley (00:06):
Welcome back to the War Against Weeds Podcast. I'm
Joe Ikley, extension weedspecialist at North Dakota State
University. My co host today isAlyssa Essman with the Ohio
State. Alyssa, how are thingsgoing in Ohio?

Alyssa Essman (00:20):
Good. We've got a nice, sunny, dry day that we've
had for many days now. How arethings in North Dakota?

Joe Ikley (00:27):
We've got a chance of up to a 10th of inch of rain
tonight. So that will be themost since about mid August. So
time to get some moisture goingagain. Well, that's not why
we're here. So we've got acouple of guests on today, and
today's topic, we're going totalk about herbicide
development. And so we pulled acouple of different folks in

(00:51):
from different industrycompanies. We're going to go
ahead and introduce them, letthem talk about what they do
within each company. So I thinkfirst we will start with Cara
McCauley, welcome, Cara.

Cara McCauley (01:03):
Awesome, Thank you, Joe, glad to be here and a
member of the war against weedsarmy that that you and Alyssa
are taking up. So my name isCara McCauley, and I am a
herbicide biologist here atcorteva agriscience, and I'm
based at our global headquartersin Indianapolis, Indiana, and so
my work over the last six or sixyears or so at corteva has

(01:26):
really been focused in herbicidediscovery, which is a necessary
part before we are able todevelop those into products. So
excited to talk with you alltoday.

Joe Ikley (01:36):
All right. Thank you. Looking forward to it. And the
next we'll go down to JasonAdams, Jason, same rundown that
Cara just gave.

Jason Adams (01:44):
Perfect. Yeah. Thanks Joe and Alyssa for having
me on. I got to start off bysaying, Go Bison NDSU graduate
here. So happy to be with youguys. So my current role is a
research and development groupleader at our Vero Beach
Research Center down here inFlorida, and I work for the weed

(02:04):
control team. And so my team andI, we work on different
development trials, very appliedresearch as part of the
development cycle for newherbicides as they are being
worked on, for Syngenta cropprotection.

Joe Ikley (02:19):
All right, awesome. So you know, one of the key
reasons I wanted to get both ofyou guys, besides knowing you
and calling in favors tofriends, is that Cara is kind of
on that front end and Jason ismore on the back end. So I
thought it'd be goodperspectives with a couple of
different companies. And so kindof gets us into our next
question. I think we'll, we'llstart with Cara on this one,
since she's on the early side ofit, but within your company,

(02:42):
what are the different stages ofwhat to say, discovery and
development? What does thatprocess generally look like?

Cara McCauley (02:49):
Sure, yeah, I can take a first stab, and then
Jason, you'll definitely have tohelp me out on the back end, you
know? So we really view ourstages of herbicide development
starting with discovery, right?So we have discovery, kind of a
pre development stage that mayhappen after that, before we
truly go into, you know, theherbicide development, really
trying to make a product out ofit. Then we kind of transition

(03:09):
to a launch phase, and then, youknow, following that, we're
still supporting that molecule,and then some type of an
extension or an improvement ofthe original use of that, you
know, so very, very shortoverview, right, of what could
take, you know, anywhere from10, 12,15, years, right? Even
that, that extended, improvedpiece that could be another, you

(03:30):
know, 15-20, plus years, right,with, with some of our
molecules, or even longer, andso, you know, within each of
those stages, right, there are,you know, there's a lot of cross
talk, right with the weedscientists. You know that we're
chatting with here today, butalso a lot, a pretty big team, a
collaborative effort across alot of different, lot of
different groups here atcorteva,

Joe Ikley (03:53):
Similar, different at Syngenta. Jason?

Jason Adams (03:56):
Yeah no, it's very, very similar. You know, we've
got for us. We break it downinto four stages. And so our
first stage is like Cara wastalking about, it's really our
Discovery Center. Discoverystage. That's when we're looking
at different molecules, kind ofnarrowing them down, profiling
them, stuff like that. And thenwe go into stage two and three,

(04:16):
which is our development stages,and then our fourth stage is
commercial launch and supportfrom there. So, yeah, very, very
similar to the process that Caradescribed.

Alyssa Essman (04:26):
So for this initial kind of discovery phase,
where are you sourcing thesemolecules from?

Cara McCauley (04:33):
You know, what? If you can dream it, we've
probably sourced a molecule fromit, right? Alyssa, it's a good
question, right? There's a lotof, a lot of pieces that we're
looking for, right, in terms ofwhat could be our next, you
know, herbicide, herbicide modeof action, or even a starting
point to a new herbicide mode ofaction. You know, we do source
chemistry from chemicalsuppliers, right? There's

(04:54):
commercially availablelibraries, certainly, that we
can purchase molecules through.And. Screen them, and our plate
based or greenhouse basedscreening, and then, you know,
those are typically goodstarting points, potentially.
And then we would then discoverand develop and create, you
know, a product from that,right? We wouldn't necessarily

(05:16):
be taking a molecule that wepurchased and taking that
through the pipeline, if onlythat, that was a possibility,
right? But it's, that's where,you know, the bread and butter
of the the scientific you know,investigation happens. We also
can, you know, novel synthesisof chemistry here on site,
right? We, I have, you know,about 60 discovery chemists that

(05:37):
sit, you know, two hallways awayfrom me, white, right? If I
find, you know, if I'm reading apaper or I have a specific
hypothesis that I say, hey,there's some molecules that I
think are interesting. Here aresome different, you know,
modifications that we couldconsider making. I look to see
if we could purchase them, andwe can't. Could we make them,
right? And that's like, one ofthe really cool parts of my job

(05:59):
is getting a chemist excited tomake a compound that that I
think has a biological target,and having them make that, and
then we can spray it on plantsas soon as they make it, and
see, see if there's anybiological effect.

Joe Ikley (06:15):
So can you just sit around, say, I wonder what 2,4-D
with a longer side chain lookslike. And you're Go, go make
this and we'll spray it.

Cara McCauley (06:24):
The easy answer is, yes. The realistic answer
is, you know, you really have toconvince someone, right? I mean,
it's a resource game, right?Just like everyone else is, is
part of right? We have moreideas, I think, than than we can
execute. So, you know, if I canprovide some, you know,
preliminary information tosupport them spending the time,

(06:45):
and, you know, buying theintermediates that they need to
do and things like that. Thosetypes of things can happen.
Usually, we're a little bit morecreative than just modifications
of 2,4-D over here. But, um, agreat idea, Joe.

Joe Ikley (06:57):
I like to keep things simple. And yep, listen, I get
the romanticized version of, ifwe can dream it, we can do it,
but yeah, we don't have thatbottom line to ultimately answer
to.

Jason Adams (07:11):
one, one thing that I'll add just a cool I mean,
it's a, it's a wholeserendipitous circumstance that
happened at Syngenta, wherethere was a particular tree that
they noticed, hey, there's noweeds underneath it. And so from
that, they were able to isolatemesotrione as an HPPD, and we're

(07:32):
able to isolate that and then beable to synthesize it, and now
it's in the marketplace. So inaddition to chemical libraries
and stuff, I've always heardlots of stories of how chemicals
come from observations ordifferent things in the field.
So like Cara said it, thesemolecules really can come from
anywhere.

Joe Ikley (07:51):
So knowing that you know, what are some of the
considerations when startingdown the pathway of discovering
development. So, you know, keyweeds, you look into control as
a company, key crops. You know,does it start as a very large
scale, looking at some importantweeds, important crops, or is it

(08:12):
just a general what does thishave activity on? Maybe we'll
start with Jason on this one.Work backwards.

Jason Adams (08:21):
Well, that's a, it's a, it's a tricky question,
so I think it's one of thosechicken or egg type discussions,
from my understanding and Caracan fill us in being more on the
discovery side. I think a lot ofthose chemistries that are
synthesized and just kind ofdeveloped, it kind of is

(08:43):
alright. What are we controllingand what, what fit does this
have and stuff, and then on thisand Syngenta, at least, all I
can say is that we start to thenlook at where does this fit. And
so some of our key, key weedsare going to vary by wheat, by
region and by country and stuff.And so, for example, in the US,

(09:05):
then some of our major cropsthat we're looking at and key
areas are going to be the nonselective market we're looking
at that we've had some successthere cereals. But then
obviously the big two are thesoybean market, and then the
grand Mac, daddy of them all,the corn market. And so we start
to find things that fit in thosemarkets. Then we start to say,

(09:29):
All right, this might besomething particularly like you
mentioned, if it's hitting someof those key driver weeds. I
think it's no secret thatthroughout the US, one of the
key driver weeds is our amaranthspecies, you know, Palmer and
waterhemp, especially with allthe resistance issues that are
out there, that's going to be akey driver. But then you've got
other ones, barnyard grass,foxtails go into the cereals or

(09:52):
the non selective market. You'regoing to add kochia,rye grass,
stuff like that horseweed fornon selective market. So, you
know, to me, it seems like it'sa chicken versus an egg, you
know. And we just kind of takewhat we get and then start to
narrow it down and see which,which market it starts to fall
into,

Cara McCauley (10:14):
yeah. And I can just, you know, add the corteva
perspective, which is again,really similar to what Jason
addressed, right? And you know,especially from the from the
discovery standpoint, we'retrying to envision what the
needs are 10 to 15 years fromnow. So we're, we have to
understand the current unmetneeds, right, which all of what
Jason included, right? If youknow the amaranthus key grasses,

(10:37):
you know things like that areimportant, but, but what might
be we be facing, you know, 2040,you know, when molecules that
I'm just now beginning tocharacterize might be on the
market? So that's a crystal ballpiece, right? That that no one
knows the answer, but I think,you know, really trying to, you

(10:58):
know, address what we have now,and using that as a starting
point, and then, you know,always, constantly evolving. You
know, what species we'retesting, what our targets are,
you know, we may have, you know,a new area of chemistry that has
a lot of, you know, promiseactivity on certain species that
may not be drivers right nowthat, you know, we keep, keep
those in mind as things, youknow, weed shifts are occurring

(11:21):
and things like that, you know.But also we can build a molecule
to expand its spectrum or startto, you know, address certain
needs that we have. So it reallyis a constantly evolving effort,
right? We have product conceptshere at corteva, which are, you
know, very well outlined byJason, right, probably really

(11:41):
similar weeds that we're goingafter. You know, we are a global
company, right? So there's theUS focus, which is, you know,
more comfortable for me tounderstand, right? I haven't had
the chance to travel over to theEU and see how terrible black
grass is in wheat productionthere, you know. But that's a
huge driver for them, you know.So we're, you know, we're

(12:02):
bringing in, you know, relevantbio types and lines, you know,
that farmers over, you know,across the ocean are facing so
it's a, it's a moving target,and it certainly keeps us busy.

Joe Ikley (12:17):
I always like to ask questions like that, because
it's, it's always interestingconversations that we'll have up
here where, you know, why, whycan't we just get a new spring
wheat herbicide? And it's alittle oversimplified when I
when I'm having theseconversations, but it's like,
yes, spring wheat is our world,but it's kind of a smaller
portion of a global profile fora global company. So always kind

(12:41):
of those tough but interestingconversations to have when a
question that seems simpleenough comes up, but almost
extension meetings,

Jason Adams (12:49):
we have that question a lot too. Joe,

Joe Ikley (12:52):
it probably comes from us and maybe Kirk Howatt
another NDSU weed scientist,

Jason Adams (12:59):
key contributors.

Joe Ikley (13:02):
But yeah, the other piece I wanted to follow up
there that you know, somethingthat I guess I haven't thought
of too often, is prettyinteresting, the fact that
you're also trying to projectwhen this product would actually
make it to market, what will bethe issues. And I know that a
lot of our older, closer toretirement extension colleagues
used to do this on an annualbasis of like, Yeah, let's what,

(13:24):
what do we think is 10-15, yearsfrom now, looking like it was
fun a couple years ago? They'relike, Yeah, we didn't really see
waterhemp coming. But let's notopenly admit that too, too
frequently. So it just justshows you can get a whole bunch
of people that work on this inthe same room, and can can
sometimes miss the mark and whatwe think will happen, because
things just evolve that quickly.

Cara McCauley (13:45):
Yeah, and you know, that's that's something
that you know, like you said,it's just the reality, right?
And when we are executing ourlab and greenhouse based
experiments, right, we're tryingto cast a very broad net right.
When we're starting out like, nokidding, What? What? 2030,
weeds. Does this chemistry maybehave activity on? How can we

(14:06):
then use that information tofocus, or, you know, maybe
delay, or, you know, push thatto the side for now, focus on
something else, right? It'salways a lot of pieces moving
together, because, yeah, youjust never know what, what next
year or the year after mightbring.

Joe Ikley (14:21):
So, kind of given all that you know what, what does
make a herbicide a goodcandidate in that early
discovery phase, just, I'llleave that open.

Cara McCauley (14:31):
I can take a stab at that, right? So first off,
you have to control the weeds,right? I'm a huge, I'm a huge
Tom Hanks fan, love, love thesolely movie, right? Don't
forget to fly the airplane,right? And I think that's
something, you know, that I'vebeen learning, you know, coming
in, coming into industry, right?You know, when I was coming up
through grad school, I was like,I mean, yeah, you have to do is

(14:52):
control the weeds. Guys like,come on, like that. That's the
easy part. And we definitelycan't forget to do that, right?
So to answer your question,right? A good candidate has. To
control the weeds in the fieldconsistently across normal and,
you know, atypical environmentalconditions, right? That's that's
not always the hardest thing todo, right? Yes, we can sometimes

(15:13):
do that, right? But thenthere's, you know, a whole list
of other things to address,right, crop selectivity, right?
I mean, unless you're going intoa burn down situation, which you
know is possible, right? But alot of times you have a crop
growing, or will be growingthere soon, right? Making sure
you're not having, you know, inany safety issues, you know,
crop crop damage on that, youknow. And then an entire list of

(15:37):
other things to consider, right,that I don't think I truly
understood before getting to theinto this position, you know,
being safe to the environment.You know, all the environmental
testing and toxicology,regulatory, you know, we new
modes of action are reallyexciting, right? But we want to
make sure that no other organismhas that that target site as
well, other than our targetweeds. You know, if we're lucky,

(16:02):
you know, it has to be able tobe formulated in a somewhat easy
to use, you know, formulation.You know, early stage discovery,
we can get a get away with, youknow, asking our field
scientists to spend a lot oftime and be pretty particular
and how they're formulating itfor our field trials. But, you
know, we can't ask for a 10 stepprocess or special water or, you

(16:25):
know, things like that, youknow, to our farmers, right? And
so I think that's the balance,you know, in early stage
discovery, we really are justtrying to to figure out where it
breaks, so that we can kind oftry to prevent that from
happening in later stages.

Jason Adams (16:41):
Yeah. And one, one thing I'd add the same, same
thing on our side is we look forefficacy, we look for crop
safety and all that, all. We'llstart to look at environmental
stuff. But in preparation forthis not being as connected to
that really early stage, onething that I found interesting,
that on the on our side, that Ifound very interesting was how

(17:04):
early they start to look atbusiness cases and cost of
goods. Because we could have arock solid product that chills,
kills weeds like nothing else,but if it's going to be $100 per
acre product, that's really hardto to say. Are we going to be

(17:24):
able to sell that now, obviouslywe're not going to have it all
nailed down in that early stageand stuff, but we can start
getting some ideas both, both,all of the companies really
have, have been through thisprocess a number of times, so
they look for key hurdles or keykey issues that might come up.
So that's one thing thatsurprised me in talking with

(17:45):
some of my early stagecolleagues preparing for this
podcast, was to find out thatreally how early on they start
to look at things like cost ofgoods and business cases.

Joe Ikley (17:57):
Yes, that kind of goes into what was gonna be my
obvious follow up was, whatmakes a product fail at this
stage, besides, it doesn'tcontrol weeds. But yeah, costs,
if you can figure it out thatearly, that definitely is an
important consideration.

Alyssa Essman (18:11):
One other question I have kind of at this
stage is, I know, in talkingwith Pat Tranel, you know,
metabolic herbicide resistanceis going to influence a lot of
things moving forward. So howmuch is that taken into
consideration when, you know,screening some of these
products?

Cara McCauley (18:28):
So I guess I can speak from, you know, early
stage discovery, right? Youknow, when we're first looking
at chemistry, where we have noinformation about it, right?
We're typically not, notscreening on on those super hard
to control metabolic resistantweeds, right? We're just saying,
Does this compound have anybiological activity on plants?
And then it kind of funnelsthrough our screening cascade,

(18:49):
and as we start to build moreexcitement about its you know,
potential, you know, to become aproduct, that's really where we
start to introduce some of theseproblematic, you know,
troublesome biotypes thatthey're out in the field. And we
do do some of that screening inthe greenhouse, certainly. But
I'm a big proponent that, youknow, you really got to, have to
take things out to the field,right? Greenhouse. I mean, I

(19:10):
work in the greenhouse, right?So it's super valid, you know,
you have to do that work, right?But controlling, even
controlling resistant weeds inthe greenhouse, first a real,
real world field scenario. It'sa big jump for new chemistry
that's not optimally formulated,right? We don't necessarily know
what it everything about thephysical properties of the
molecule, the uptake, you know,all of those things. So, you

(19:33):
know, we really have to addressthose things. And then also
consider, you know, what are theweeds that this chemistry is
going to try to control in thefield, right? Knowing that you
know increased metabolism orsome differential metabolism by
these weeds can really up end alot of what we think we
understood about some of this,this brand new chemistry, right?

(19:53):
Because there is evidence ofthat, right, where these
biotypes that have increasedmetabolic. Machinery that can
chew up existing herbicides, canalso chew up herbicides they've
never seen before, just becausethey recognize it as something
that normally, you know isn't,isn't inside the plant. And so

(20:13):
it's definitely something thatwe're focused on from a
synthetic chemistry perspectiveas well. Right? How can we
design molecules to try to blocksome of that metabolism. So, you
know, we are cued into a lot ofthe work ongoing at universities
and things like that, as they'redetermining which genes and
which pathways are involved insome of this Metabolic
resistance. And we're using thatinformation to try to build

(20:36):
molecules that would be at leastresistant to what we know now,
right? Knowing that, you know,things evolve, but you know,
trying to, trying to hit thatmoving target for sure.

Jason Adams (20:47):
Yeah, and our side, it's, it's a key, key factor. I
like how Cara said earlier onthat, you know, we've got to
have that crystal ball. Andresistance is a continuously
evolving thing that we've we'vegot to keep our finger on the
pulse. And so similarly, we haveearly stage we have entire
groups that are just dedicatedtowards looking at resistance

(21:08):
issues and stuff. But I'll tellyou on the on the development
side, the applied research outin the field side, we start
looking at it pretty early on,if we've kind of identified
that, hey, this might be amolecule that might have a
potential fit to targetresistant problems, whether
that's in the amaranthus orwhatever species it might be. So

(21:30):
even on the on the fielddevelopment side, we we start to
hit it pretty early on to justsee how that that product and
those the different moleculesthat we're testing with might
have a fit in that market. Yeah,

Cara McCauley (21:43):
and I can just say, you know, I have, I'm on a
project right now. I won't,won't spill the beans too much,
but new, it's a new mode ofaction, right, that we've
discovered here, and we'repoised to go to the field for
the first time next summer. Sothis compound, this area of
chemistry, if you will, has onlybeen characterized in the
greenhouse to date. So my firsttime going out to the field, you

(22:06):
know, summer, spring, summer2025, we have trials on
susceptible biotypes, and wehave trials on the tough to
control metabolic resistantamaranthus. So the first time a
new molecule is being sprayed inthe field, right? We want to, we
want to have a balancedapproach, right? Because I'm
really what's, what's thehypothesis, you know, What's the
objective of going to the fieldfor the first time? One, you're

(22:28):
trying to figure out, hey, iswhat I'm seeing in the
greenhouse, what I'm seeing inthe field, right from a
formulation and an activitytranslation perspective. But no,
K Am I controlling these weedsthat nothing else is
controlling. So year one, we'retrying to tackle that.

Joe Ikley (22:44):
And that leads into what I had as my next question
of, what you know, do you have agood candidate? What are the
next steps along the way of,probably past Discovery now,
with developing this, thisproduct, and sounds like Cara
started that, and so maybe wecan just continue down that
pathway, or maybe Jason can.

Jason Adams (23:01):
yeah, no, I think, I think once we have done some
of that early stage work, andwe've kind of taken taken a
product in an area of chemistrywhere we might look at several
different molecules, we kind ofget it narrowed down to one lead
candidate. We might reserve someas backups and stuff. But once
we get it narrowed down to thatone believe candidate molecule,

(23:25):
then a lot of what we're we'regoing to be working on is
basically targeting to build acomplete and robust label. You
think about the labelingrequirements and everything that
we got to have to launch that aproduct to market. The labels
contain all that information. Sowe got to start looking at

(23:46):
rates. We got to start lookingat timing of application. We got
to start looking at Broad weedspectrum, as well as our
targeted weed spectrum. We'vegot to try to capture different
soil types, differentenvironmental conditions,
different varieties or hybridsof crops. We've got to start

(24:07):
working formulations, Cara's,mentioned early on, you know,
the formulation we, we kind ofstart working at an early stage,
but we don't really, you know,tweak it and finalize it till
that development stage. Sothat's, that's a lot of work is,
is a lot of formulation workthat goes on. Adjuvants are

(24:28):
going to be a key factor, tank,mix partners, product concepts,
weed control programs. So, Imean, the list just goes on and
on. But the way I like tosimplify it is, at the end of
the day, we said, Okay, this isa candidate we want to move
forward with. Assuming we'resuccessful, we've got to write a
complete and robust label tohelp give all the instructions

(24:50):
that are necessary to have thatproduct successful in the
marketplace. And so those arethe sorts of questions that we
start to just click off and.Target with our different field
trials throughout the years.

Joe Ikley (25:04):
So what's that timeline kind of look like for
greenhouse portion of screeningthis molecule? Some that early
stage field probably allinternal at this point, and at
some point you get to ship itout to folks like me to play
with once in a while.

Cara McCauley (25:20):
I guess. Yeah, I can take a take a start to that
one. So, I mean, I thinksometimes it's easy to think,
Okay, we have a molecule, right?So you're going to test it in
the greenhouse for a coupleyears, then you're going to go
to the field, and then internaltrials, right? And then
cooperative trials,unfortunately, usually there are
some, some u turns along theway, right? You know, as you

(25:40):
know, we may have a couple yearsof greenhouse data to support a
field, a field candidate, right,which is a huge jump for me as a
discovery biologist, right?Getting to take a molecule out
to the fields at a pretty bigdeal, and not something that
that you just run a couplethings in the greenhouse and you
get that type of support. And soI think you go to the field the

(26:00):
first time, fingers crossed,right? That it translates based
on what you're you're expectingto see, but most of the time it
doesn't right. Could it havebeen a formulation issue we've
been talking about that someright? You know, is there an
unexpected result that then youhave to kind of de functionalize
what you observed, to try totease apart the pieces to figure

(26:21):
out what was the contributingfactor to, you know, a lack of
translation situation, right?Could it have been that, you
know, the field scientistsformulated it and then it ended
up raining, and so it sat in thewater for 24 hours, which was
unexpected, and they went aheadand sprayed it, because usually
that's fine. But then we laterfound out that the physical

(26:42):
properties of the molecule weresuch that 50% of it was degraded
because of the water hardness atthat field site, right? I mean,
there's so many little piecesthat you really have to control
you can control right? But alsoknow that that there's some
variables that you know thingsdon't look as expected, that you
have to kind of come back to thedrawing board and then redo

(27:02):
those trials again the nextyear, right? Or, you know, go to
a, you know, the southernhemisphere or something to drag,
get a trial. And, you know, theUS winter, right? Take, you
know, ship, ship, some sample,down to Brazil or something
again. Then the the wheatspectrum is different there. So,
you know, what is the objectivethat you're trying to achieve
there, right? Just, hey, does itwork in the field, or, Hey, does

(27:24):
it work on the bio types of thespecies that we have down in in
South America, versus what ourtarget was in North America? And
so a lot of a lot of thosecomplexities, right? Can really
extend the number of times yougo to the field, quote, for the
first time, before you're ableto finally replicate, replicate
those, you know, and wementioned, right? You just, you

(27:45):
have one, one lead, right? Jasonmentioned, you kind of, you
know, one analog, maybe somebackups, but it might be that
you have a lead. And then, youknow, after going into the field
for two or three years, yourealize that that's doesn't have
a path forward for one reason oranother. So now you're going
back to your backups, or yourbackup backups, or something
like that. And I think that'sreally what can extend the

(28:08):
timeline due to the field seasonand the testing nature of the
new herbicides.

Jason Adams (28:15):
That sounds to me like corteva has a lot of the
same fun situation that I andthat's exactly right. You know,
the way I answer that question,Joe is, what's the general
timeline of greenhouse to fieldto internal external? It's a
messy web of back and forth andall around, and it's just kind

(28:39):
of a gradient, because I knowfrom from my perspective and
what I see, we might be gettingsome compounds down here in Vero
Beach, that it's the first timeit's seen outside of the lab at
our Discovery Center, which islocated in jets Hill in England,
might be the very first timeit's seen Outside of that, that

(29:01):
setting, but then it goes backto gelato, back to the lab, back
to greenhouses and stuff. Thenit goes to the field here in the
US. But then so just all overthe place and and there's no
straight line path fordevelopment and what it what it
looks like, because we weencounter all sorts of crazy

(29:21):
twists and turns along the way,like Cara is describing. So I
thought she described it very,very well.

Joe Ikley (29:28):
Kind of reminds me of that the it's been a meme now,
but that picture from It'sAlways Sunny in Philadelphia,
where Charlie's there with allthe pictures on the wall and red
string going to all thedifferent pictures.

Cara McCauley (29:42):
right, yeah. Sometimes I feel like a
herbicide biologist. Sometimes Ifeel like a detective trying to
investigate a situation, and youhave to do like interviews with
all the relevant parties to tryto figure out what may have been
involved there, right? And kindof Yeah, making a web of you. Of
brainstorming, right, to try tofigure out what, what could have

(30:03):
gone wrong, right? Which youknow Joe, Joe, Alyssa, both of
you, you know Jason as well,right? We all kind of grew up,
right, conducting, you know,field research as weed
scientists. And even withlabeled herbicides that we've
had around forever, you getunexpected results, you know,
and you're not sure, was itdifferences in humidity or
rainfall or you name it, right?And it's kind of those same

(30:26):
issues, or what we're facing aswe're trying to develop new
herbicides. Yet we have thisunderlying lack of information
about historical performance ofwhat we like really can measure
back to so it's kind of tough tokind of just keep yourself in
aligned and you know, movingforward, that's

Joe Ikley (30:46):
impossible to account for every scenario. But that's
good, because I think it'simportant for for all of us,
whether we're the four of ushere, anyone listening, we
always hear the number of x,number of hundreds of millions
of dollars to develop a newproduct. And this is just a
piece of that. We're not goingto touch all the environmental

(31:07):
and toxicology stuff, but justseeing some of this back and
forth that may happen early onfor a candidate that gets there,
you can start quickly racking upsome dollars in your head if you
figure out how much that mightcost.

Cara McCauley (31:20):
Yeah, I was reading an article, I think came
out in February from from croplife, and it said, it's, we're
now, you know, north of 300million for a new AI in minimum
12 years from identifying theactive first synthesis to
launch. I think that would stillbe a pretty rapid timeline, you

(31:43):
know, just in terms of all thethings that that you may have to
all the obstacles you may haveto overcome right along the way,
like I had, I had a project lastyear where, you know, the like I
mentioned, physical properties,right? Not something I'm super,
you know, well versed in, wasn'tpart of my education, but the
physical properties of thesecompounds were such that they

(32:04):
weren't able to be read in someof our regulatory studies. They
just weren't conducive to theway that study was was set up,
you know. So we almost missed afield season because, you know,
we couldn't go out to the fieldwithout this critical
information, and so we're justracking our brains like this has
never happened before, right?How do you how do you navigate
this new problem we have, youknow, amazing teams of folks.

(32:27):
I'm sure Jason has a lot ofcolleagues that he he reaches
out to, right? We don't have tobe the experts on these, but
it's just things I never reallythought might hinder herbicide
discovery and development arethings that I have to face
almost on a daily basis here.

Jason Adams (32:46):
Yeah, and like Cara mentioned earlier, one of the
tricky parts is a lot of timeswe don't know what we don't know
and stuff. And so we might seesome unexpected results in the
field, and we come back and youknow, some of us might might
want to know something aboutabout that product. I'm going to
go back to my days at NDSU andKirk Howatt always asking me

(33:08):
about pKa. It's one of hisfavorite topics. It's like a
requisite to get out of thereis. It really, really is. But,
you know. And sometimes we weknow that, especially the later
that a project goes on, we'regoing to have some of those
answers. But really early on,maybe that first look in the

(33:30):
field, we're going to have thatunexpected result, versus we're
going to say, Well, what aboutthis or that? We may not have
that piece of information yet,which then makes it really
tricky to then say, Okay, well,how do we, how do we solve that
problem? How do we, how do weaddress it and stuff? So I think
it's, it's key. And Caramentioned that there's, you

(33:52):
know, we both play a very smallrole in the overall development
and process of getting aherbicide to market, where
there's whole other teamsinvolved in stuff, and so it's
interesting for us where, Imean, we're on the phone with
different people all the time,whether it be England or
Switzerland, where our globalheadquarters are, or just

(34:14):
wherever, we're on the phoneconstantly with random groups of
people trying to get answers toquestions, to try and drive
things forward.

Joe Ikley (34:23):
So what happens? I'm thinking now you got this
awesome candidate, it's clearedevery hurdle. Then you send it
to us university folks, and nowthat now the net is wider, and
just say, you send it up toNorth Dakota, and we get some
weird crop injury or somethingcompletely unexpected, but you

(34:43):
still want to move forward withthat product. Is there a
standard operating procedurehere? What are the next steps in
that?

Jason Adams (34:50):
Joe that would never happen? You would never
mess up anything, right?

Joe Ikley (34:56):
No, not every soil in North Dakota is unique or
anything.

Jason Adams (35:00):
No, no, it's not well, I'll start here, because
what I'll say is that here atthe Vero Beach Research Center,
this is kind of our bread andbutter. That's a lot of what we
do within my team is because ofthe facilities that we have,
because we're in Florida, movingdown here from North Dakota. I

(35:22):
can tell you, the weather ismuch nicer in January down to
here. And I can have corngrowing in the field, or I can
have wheat, or I can havesoybeans or whatever growing in
our fields down here, or ourgreenhouse facilities, or our
growth chamber facilities. Andso we have a lot of those

(35:43):
situations where somethingunexpected comes up during the
field season from testing,whether it be internal questions
or coming from our externalcooperators, these questions
come up. And so what we'll do iswe come down, and we'll work
with our technical managers whoare stewarding these projects as
they're being developed, andthey'll come up with questions.

(36:07):
And so in a lot of cases, wekind of tack it, tackle it very
academically down here at theVero Beach Research Center, and
say, Okay, well, how can wefigure this out? And so we might
start looking at the situationthat Joe encountered there in
North Dakota. We'll startlooking that particular

(36:27):
situation, and we'll startbreaking it down and say, Okay,
was it wetter than normal? Wasit drier than normal? Did we
have hotter than normalconditions, or colder or
whatever? And because of some ofthe facilities that we have
here, we can start to break thatdown and run individual, kind of
sequential experiments to startto say, Hey, is it the cold, wet

(36:50):
that causes more problems? Is itdifferent soil types? I know
we've had, we've had situationsout of North Dakota, and so
we've had, we've had soilshipped from North Dakota, from
those fields down here, and weput them in pots. We put them in
the greenhouse in December,January, and we run a trial to

(37:12):
try to identify what may havehappened there. And then one of
the key things is to not justfigure it out, and it's one
thing, and that's great. Okay,we identified that it's XYZ
conditions that cause theproblems. But then we go back to
our discovery teams, or ourformulation teams, or whoever it

(37:34):
might be, and we take thoselearnings to then circle back,
like Cara was describingearlier, we take that, and we
might have to take a littleabout face and all right, what
do we need to change? Whetherit's formulation or it's a use
pattern or label language orwhatever? And then we take those
learnings, and then we justcontinue to move forward. But I

(37:57):
think the key is to circle backto all those entities that are
involved to learn from eachother and work together to drive
a solution forward.

Cara McCauley (38:07):
Yeah, I would just say the corteva perspective
is the same, right? I mean,again, I'm not working with any
industry cooperators yet. Maybe,you know, maybe my projects
might make it up to NorthDakota, over in Ohio. Alyssa,
you know, would love that. But,you know, it's the same thing.
When I'm encountering fieldtrials, right? Try to replicate
what you saw in the field using,you know, growth chambers. You

(38:29):
know, we've, we've shipped soilfrom the Northern Plains as
well. I don't know what you guysare doing up there, no, um, but,
but, yes. I mean, usually, youknow, you know, like I said,
trying to tease apart what, whatcomponent of that trial was, was
giving, you know, atypical,atypical results, right? One
thing I've also encountered,right, is, is different nozzles,

(38:49):
right? You know, you youidentify, you know, a couple
nozzles that are working reallywell, right? And then you put
that in your protocol, and, youknow, most of the time it
happens, but sometimes, oh, Iforgot to change my nozzles out.
You know, that could have beensomething that contributed to
some differences. You know, allthe things that we've learned

(39:10):
right through our Weed Scienceupbringing, you know, all of
those pieces are still in play,you know, as we're trying to
discover new herbicides.

Joe Ikley (39:19):
Yeah, so bonus question here, I didn't quite
prep before, so we'll see howthis goes.

Jason Adams (39:26):
I'm scared.

Joe Ikley (39:29):
Now we get to the launch year the product, and now
it's in a lot more people'shands. What would be the general
case of then, if you have acouple areas pop up of issues
and not thinking widespreadissues, but like, certain things
happen, and there's feedback ononce we got it out there,
because we did all sorts ofweird tank mixes, all sorts of

(39:50):
different environments, nozzles,all that happens is that that a
different set of people than youguys. I didn't prep you for it.
So there's your easy out there.

Jason Adams (40:00):
so for for my perspective, Joe, what I'd say
is the process really doesn'tchange from this in Syngnta
side. It might change a littlebit on the field side, but
certainly we we encounter thosesituations. One of the famous
quotes that kind of circlesthroughout our organization is
things never look as good asthey do in test plots. And so

(40:24):
you got people like the four ofus on this recording right now
that we take every effort tospray with the right nozzles and
right pressures and right boomheight, and every single thing
we're controlling, all thosefactors to make a really quality
application as it moves out tothe field commercially, maybe

(40:46):
it's a little bit different.Sometimes it's up and so there
again, here at Vero Beach, we doa lot of a lot of commercial
support programs and trials totry and answer some of those
questions. It might go I likethat. Cara mentioned application
technology, nozzles and andspray patterns and stuff like
that. We have a group that mightget involved on that side, but a

(41:11):
lot of it for for at least thisin Syngenta, follows a lot of
the same kind of processes tocontinue to work and make sure
that our products are being usedeffectively or and that we
continue to answer questionsabout them.

Cara McCauley (41:28):
Yeah? I would, yeah. I don't have a much, much
more to add for core tablet,right? I haven't really, you
know, dealt with anything goingto launch, but echoing
everything Jason said, right? Imean, you just, you encounter a
situation, you figure out whatthe issue is, you assemble a
team to tackle it, right? And Ithink when you're at a launch
scenario, right, the elevationof the issues, you know, are

(41:48):
probably going to be a littlebit different than when you just
have a couple of field, internalfield trials that don't look
look as expected, but all thesame, all the same science
backing up the decisions thatwe're making, and, you know,
educating others, right? I thinkthere's also a big piece of on
behalf of the companies, thatit's our responsibility to
educate people how to use usethe new technology to get the

(42:12):
result that everyone'sexpecting.

Joe Ikley (42:16):
And lot of times in those post launch things, that's
when folks like Alyssa and I getto get involved sometimes, of
walking to the field and whatthe heck happened here? Yep.
Alyssa did you have a questionearlier?

Alyssa Essman (42:31):
So we touched on this a little bit earlier,
talking about spring wheat. Butin general, one of the questions
I think Joe and I both probablyget a lot is, you know, when's
the next big, new, excitingproduct? And of course, I'm not
asking you to give away companyor trade secrets here, but I'm
just curious, are there anymolecules or any specific
projects you're excited about?

Jason Adams (42:52):
I'll let Cara go first.

Cara McCauley (42:54):
Okay? Challenge accepted. You know, yeah,
Alyssa, it's a fair question,right? And you know, we get it
all the time. And I'm sure, youknow, everyone listening to this
podcast has probably at leastasked or been asked that
question before. You know, I cansay we do have, you know, some
really exciting new herbicidemodes of action in our pipeline
for corteva that arecontrolling, you know, the

(43:16):
driver weeds that we talkedabout. You know, it just is a
matter of, you know, navigating,you know, the necessary hurdles
to make sure that we can get alabeled product out of it and
into the hands of farmers. Youknow, there have been molecules
in our pipeline that get dephased right when you know,
problems come up that that thereis not a way, necessarily, to

(43:39):
navigate it towards a solutionthat that results to a new mode
of action or a new technology inthe farmer's hands. So we're on
it. I hear you, you know, everyday I'm commuting to work
thinking, all right, you know,how can I, you know, how can I,
you know, help this war againstweeds, right? With a new

(43:59):
herbicide technology, mode ofaction, you know, formulation,
all those different things. So,so we're doing our best, but
certainly, certainly, it's amoving target that that we're
after.

Jason Adams (44:12):
Yeah, and on the Syngenta side, it, it's the
same, you know, we we have thesame questions, the same
concerns. It'd be really awesometo bring out a new mode of
action. We all, we all aresearching for that and trying to
make it work. It's tough.There's a lot of hurdles to get
there. And saying this car, Iwon't, you know, give away too

(44:32):
much, but on the Syngenta side,we have a we have a number of
very exciting new products thatwe are working on and that are
so far progressing quite nicely.It's up, but you never know what
tomorrow is going to bring. Butright now, in the herbicide
space for Syngenta, I'm very,very excited about what the

(44:52):
future might hold.

Joe Ikley (44:54):
And there's always surprises. I remember an older
think he's retired now, so I canI. Talking generalities, but a
different company had a productthat was almost there, but then
in I think it was like an eyedrop test on a on an animal in
the lab. Some, some of thetoxicology stuff didn't go well.

(45:15):
And it's like, well, if youknow, once you get into the
toxicology side of things, ifsomething goes bad, that might
kill a product, right there? So,

Cara McCauley (45:23):
yeah, and that's something where you know, is it
a mode of action issue, right?That the mode of action that
we're targeting is somethingthat is relevant in humans,
right? That's definitelysomething that we work to avoid,
right? Or is it a moleculeissue, right? Is it just
something about that, thatactive ingredient specifically
that caused that issue, and thatyou just need a different

(45:44):
molecule that might not havethat same, you know, unexpected,
you know, regulatory results. SoI think those are the the two
ways to kind of think aboutthat. Yep,

Jason Adams (45:55):
we've had that happen here too. That happened
early in my time down, down hereat Vera beach, we were working
on a project, and then we gotthe email that something,
something somewhere else hadfailed and cease and desist.
Over overnight, you know, wentto bed, think it all was well
and really excited the nextmorning, cease and desist. So

(46:20):
it, it can happen and it and itcan come from anywhere. So you
just, you never know whattomorrow's going to bring in
this herbicide development

Joe Ikley (46:27):
game. I've got one more bonus question I thought of
along the way.

Jason Adams (46:34):
Hey, we talked about this, Joe. The surprises
is where I get in trouble.

Joe Ikley (46:42):
I like to live on the edge. And this, this one
actually may vary by company,and you may not know the answer.
Again. Bonus question that popsin my Pea brain as we're talking
at what phase in this do youdiscover the mode of action or
site of action? You know, is itbefore you even sprayed in the
greenhouse, or is it? It killssome weeds. Now, let's kind of
delve into this.

Cara McCauley (47:04):
So I would you know in terms of the stage of
herbicide development, typicallyin the discovery stage is when
we're determining what the modeof action is, in terms of your
kind of second, your second,second. Bonus question, you
know, sometimes we are sprayingactive ingredients or molecules
in the greenhouse where we don'tknow what the mode of action is,
we may we, I guess, always havea hypothesis, you know, around

(47:27):
what that molecule might be. Andit could be that the molecules,
you know, true hypothesis isthat it may have a target from
an insecticide or fungicide orpneumatic side perspective. But
we'll go ahead and throw it intoour, you know, herbicide
screens, because you never know,right? And so I think early on,
and you know, if it's a trulynovel hypothesis, right? Or if

(47:50):
it's not one that was herbicidein nature, we may not know what
the mode of action is for acouple iterations of our
greenhouse testing. And I thinkit's a resource game there as
well, right? Is it worthfiguring some what the mode of
action is of a molecule, if wereally don't care too much about
it, right? You kind of have to,you know, the chicken or the
egg, you know, as Jasonmentioned earlier, right?

(48:11):
Sometimes you have to prove thatthis molecule is interesting
enough to warrant the resourceto determine what the mode of
action is, right? And sometimes,sometimes, the the methodology
there is, first, you prove thatit's not something known, right,
those are pretty easy assaysthat we can run to eliminate
known modes of action, and thenyou're in this, you know, phase

(48:36):
of well, it's just not somethingthat we know, right? That's a
lot lower bar to investigatebefore going to the Okay, what
is the site of action? What isthe mode of action? And even if
you find the site of action, youmight not know the way the plant
dies, because that site or thatmode of action is inhibited in
some way. So you know, this iswhere you start to think, Oh,

(48:59):
these are multiple PhDs worth ofeffort to figure out what a mode
of action is, or, you know, howit works to control the plant or
not control, you know, the crop,or things like that. So, I mean,
I think it's a great question,because this is part of why I
got so excited about herbicidediscovery and really wanted you
know this type of career path isthat you really get to spend

(49:21):
time iterating through those,you know, experiments, trying to
figure out, you know, using yourherbicide symptomology, right? A
huge call out to everyonecompeting in the contests,
right? You know, part of my jobis going up to the greenhouse,
looking at compounds that havenever been spread on plants
before. And I say, Does thislook like anything that that we
know, and am I excited about it,right? And that really is the

(49:43):
starting point that that some ofthese new herbicide products are
right. Someone sees it in thegreenhouse and says, Hey, that
looks good. That is worth somefollow up. And then we have 99%
of the things that come throughour early stage screens. That is
an interest. You know, that.Aren't interesting. There's no
follow up, right? We're reallyjust looking for, for that, that

(50:04):
special active ingredient ormolecule to spark our interest,
to then warrant the follow upfrom a project, and, you know,
getting out to the field andseeing if it can go into a
product eventually,

Jason Adams (50:17):
yeah, and I'd say on our side, it's probably very
similar. I don't know the wholediscovery side of when they're
looking at it, but all I can sayis, I mentioned a lot of times
we might be some of the firstpeople outside of gelatin to see
a product. Most of the time wehave at least an idea of what
the mode of action is by thetime it gets to me. So it has to

(50:40):
happen pretty early on, at leaston some level. Again, like Tara
said, we might not have everysingle thing figured out about
it, but we've got at least someidea by the time it it comes to
us here, here in Vero.

Joe Ikley (50:56):
Thank you for entertaining my bonus questions,

Cara McCauley (50:59):
anytime Joe, anytime.

Joe Ikley (51:02):
Alyssa, do you have any?

Alyssa Essman (51:04):
only one quick question? I think this is an
easy softball question, so we'vebeen asking folks for the past
season or so. Is there a silverbullet for weed control?

Jason Adams (51:22):
I've got gonna say no, I don't, I don't think there
is one. I mean, I Yep, I'm justgonna stick with no, and then
we'll let Cara tackle the finerdetails. You're welcome, thanks.

Cara McCauley (51:38):
Thanks for setting me up for success there.
Jason, yeah, I agree. No,there's not. I mean, if only
there was, right? I mean, thatthat would be fabulous, but I
don't see it right. I mean, Ithink just in all you know,
everything we've observed thelast 510, 1520, years, you know,
in terms of how we'recontrolling weeds, it's we're

(52:00):
constantly evolving our tactics,right? You know, don't get me
wrong. I, you know, I love myjob as a discovery herbicide
biologist, right? But there'smore out there than just
finding, you know, a new mode ofaction, a new molecule to
control the weeds that we have,right? About every tactic that
we've come up with, weeds areevolving, you know, resistance

(52:22):
to it, right? Not just thechemical strategies, right? You
have, you know, weeds arechanging when they're dropping
their seeds, which is makingour, you know, weed seed
destruction. You know, effortsless, you know, less
efficacious, and things likethat. So, you know, I think, to
me, there's no silver bullet,and that that's okay, because

(52:42):
we're all in it together toprovide, you know, the insight
and the technology, you know,that we all have, and it comes
together as a collective right?I think that's what's really
cool about this podcast, right?You're bringing in folks from
all different experiences, butall with the desire and the
passion for weed control, right?I mean, and you got to be

(53:03):
honest, no one grows up wantingto become a weed scientist,
right? It's not, you know, noton the top 50 or 100 career
paths, right? But, but it's,it's been really fun to really
start to build my network andsee, hey, everyone's just trying
to figure out one piece of theirpuzzle, and then, you know,
sharing that for others. And Ithink that that's the path
forward, right? Providing, youknow, maybe I can help provide a

(53:27):
chemical solution, that that'sthe goal, right? That's, that's
the dream, but that, but there'smore to it, and it's certainly
not going to be a silver bulletthat that comes to our rescue.

Jason Adams (53:38):
We haven't gotten one yet, so I don't I don't know
what we expect to change in thefuture. So

Joe Ikley (53:46):
here you need to take my mom's tactic when she tries
to brag about me, she'll justsay, I'm a doctor, and to stop
there, and stop all the actualimportant details that follow
that. But then I make that top50 list of desirable careers.

Cara McCauley (54:04):
we all just want to be doctors when we grow up
right?

Joe Ikley (54:09):
All right, last thing for both of you, which we do
like, to provide our guests anopportunity. If you have any
social media places you wantpeople to find you time to pitch
that. I don't know if either ofyou is active on Twitter or X
that I have found.

Cara McCauley (54:25):
I'm not not very active on social media, both
personally or professionally. Iguess I do have a LinkedIn. So
if anyone listening wants tofind find me on LinkedIn. Feel
free to connect. Send me amessage, if you'd like to follow
up on anything that we talkedabout, happy to to to answer any
questions there.

Jason Adams (54:46):
Yeah, same, I'm on I'm on LinkedIn. But past that,
the social media game is, is notmy strong suit in life. But same
as Cara, if anybody wants toreach out and connect that way,
then happy to do so.

Joe Ikley (55:01):
All right, we can post those in the show notes,
and assuming people check thoseevery now and then, but LinkedIn
is where to find these two. Sowith that, I do want to thank
both the guests. I want to thankthe listeners, and we will catch
you the next time on War AgainstWeeds podcast.

(55:26):
As always, we thank you forlistening to the War Against
Weeds podcast. Just anotherreminder. You can find our
podcast hosted on the CropProtection Network, or CPN, for
short. So this is another greatresource that's driven by
extension, scientists atdifferent universities for pest
management, and with that, wewill see you next week on the

(55:46):
war against weeds podcast.