science matters : summer 2008

From weevils to weeds,Biokinetics is revealing theeffects of our products

Syngenta scientists areintroducing new blood intothe elite stock of maize

Thanks to a dedicated Toxicologyteam, Thiamethoxam is now ableto fight pests

From flowers to mosquitoes, toherbicide resistance, read howSyngenta scientists are achievinggreat things

TheA toZof field testsApples are just one crop testedby our global field testing team

sciencematters

Keeping abreast of Syngenta R&D Summer 08

ScienceMagazine3.1:Science magazine 27/8/08 15:40

The photograph shows a micropscopic picture of the meristem of Sorghumhalepense (Johnson Grass - a weed) taken by Jill Foundling at Jealott's Hill.


Recently I met John Beddington, the UK Government’s Chief Scientific Adviser. He isresponsible for providing advice to policy makers and direction to the government onscientific issues. Top of his “worry list” were food security and energy security, relating tothe key drivers of climate change and population growth, as well as the development ofnew infectious diseases. It is interesting to see how these are so directly relevant toSyngenta science.

The food price crisis has been described as a wake up call to the world by JosetteSheeran, the head of the UN World Food Program. There is growing appreciation of theimportance of obtaining high yield from existing farmland, but in a sustainable way. Indeed,Jason Clay from the World Wide Fund for Nature (WWF) recently stated “..the answer isfor farmers to become productive…any thinking environmentalist would want to see moreintensification of agriculture.” While this is a really positive contribution to the debate, I amsure that not everyone shares this view. It does reflect their analysis of how to protect asmany of the wilderness areas and rainforests as possible while rising to the challenge ofdoubling agricultural production by 2050.

Another crisis facing the world is the curse of malaria in Africa, where a child dies every 30seconds from the disease. Syngenta science is at the forefront of finding solutions to helpprevent this terrible death toll and in this issue you can read about one of our projects,improving the effectiveness of anti-malarial bed nets.

Our business results show that our technology has never been in greater demand, andincreasingly key stakeholders are talking with Syngenta as a key contributor to setting thescientific direction for world agriculture. Syngenta Chairman Martin Taylor said recently:“Great financial results are built on millions of non-financial actions.” This issue of ScienceMatters covers a variety of topics where our science and scientists directly support ourbusiness in harnessing new scientific knowledge in the creation of new plant varieties andchemical technologies, in supporting our products in the market place through theinfluencing of regulators, the logistics of supply and technical support to growers.

Our science has never been more important, and the great news is that the best is yet tocome!

Mike Bushell

Our science hasnever been moreimportant

Science Matters Keeping abreast of Syngenta R&D Summer 2008

Contents

Biokinetics: it’s the weevil’s 04knees of a problem

Time to introduce some 06new blood into the elitestock of maize (corn)

Toxicology team ensure 08that ants don't win

Product Biology: the sun never 10sets on Syngenta field trials

A bouquet for De Lier 12

Steve Goff’s off to Arizona 14

Seven jumbo jet loads 16of children crash intomosquitoes every day

Herbicide resistance: an 18opportunity for Syngenta!

Syngenta Fellows Annual 20Conference 2008

Carolyn Riches goes 22Out and About

03


Biokinetics is the study of everything that happens from the moment a pesticidemolecule lands on its target – be it plant, fungus or insect – to the instant it strikes thesite of action. Syngenta’s Dave Bartlett explains just what his group does and theproblems they have to overcome.

Biokineticsit’s the weevil’s knees of a problem

04 Science Matters Keeping abreast of Syngenta R&D Summer 2008


The Biokinetics Group is a global

resource and works on all herbicides,

fungicides, and insecticides used on the

world's major crops. In addition, his

group has worked on such diverse areas

as turf grass, horticultural plants,

mosquito nets, shower curtains, and

even concrete blocks. The group works

across all phases of the business from

early-stage chemical synthesis, through

optimisation and development stages,

and finally to established products in the

marketplace. A key part of his work is

studying how Syngenta materials

compare with competitor molecules.

Dave: “The biggestdevelopment over the lasttwenty years has beenthe increase in analyticalsophistication both interms of the ability toquantify molecules and toidentify their metabolites.”

Visualisation has come on a long way

too, especially in terms of image

resolution and manipulation; Syngenta

was the first to use phosphor imaging

routinely as a method to visualise

radioactive molecules in plants as part of

the ‘selling story’ and this has been a

consistent feature in technical launches

for many of Syngenta’s products.

Dave: “We study all the parameters that

can influence how a pesticide behaves in

the time-frame of its biological effect, this

can mean from minutes to months.

There are many factors which influence

the way a pesticide works such as spray

retention, redistribution on the target after

spray, rain fastness, vapour movement,

uptake, translocation in and on the plant,

and the rate of degradation of the

molecule. All are quantified to establish a

picture ofwhywesee the effects thatwedo.”

But it’s not always that easy, as Dave

says: “We also need to explain why we

don’t see the effects we expect so see!”

The Biokinetics group operates in

controlled environment facilities such as

glasshouses, and, with increasing

frequency in the field, working with

product formulations using commercial

sprayers – and on farms as well, which

are the macro end of the process. At the

micro end, the group’s research involves

being able to observe what is happening

on the leaf, insect or fungal surface itself.

Microscopy is a fundamental part of

understanding the whole biokinetic

picture and the group use electron, light

and confocal microscopy techniques to

visualise events on and in the target.

Dave: “In the last five years we have

become increasingly involved in research

for the seeds, flowers and vegetable

businesses. We’ve even looked at the

way harvesting can be made easier, for

example making courgettes (zucchini)

easier to pick.” And it’s not just plants and

pests which they look at. They also carry

out visualisation of wood, tree trunks,

termite barriers, hairs and even the leg

joint of a weevil. Dave says that ant

colonies have also featured in their work.

Dave: “It is in the development and

marketing areas where I think we have

had most impact over the years and

where there have been some unique

opportunities to become involved with

global product launches and ‘key

influencer’ events, telling the biokinetics

stories behind how Syngenta’s products

deliver their effects.”

As Dave says, it’s all been about

“influencing the influencers” and one of

Syngenta’s biggest successes has been

in the story of the azoxystrobin based

products, especially Amistar®, Quadris®

and Heritage®. Along with plant

pathology, resistance biology, chemistry,

regulatory and environmental stories, this

was the first time that a concerted

science platform had been taken out to

the wider world and been presented by

the scientists themselves.

SowhatwouldDave like to see in the future?

Dave: “The biggest advance would be an

ability to visualise chemical localisation at

a cellular and sub-cellular level. Ideally we

would do this without using radio-labelled

molecules, and to do this with the same

‘point-and-shoot’ ease and sensitivity

that we can with radioactively labelled

materials in whole tissues. There are

techniques out there, but nothing that

works in the timeframe we need to work

in – yet.”

In 1979 Dave Bartlett graduated from the

University of Bath, UK, with a degree in

applied biology and went to work for the

Soil Science group at ICI. In 1985 he

moved to the US to work with ICI

Americas carrying out regulatory studies

on the compounds which were eventually

marketed as Force®, Karate® and Cultar®.

Then in 1990 he came to Jealott’s Hill,

joined Exploratory Plant Sciences (Plant

Physiology section), and set up what

became the Biokinetics Group.

05Science Matters Keeping abreast of Syngenta R&D Summer 2008

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There’s exotic maize and elite maize. The former varieties are the uncultured ruffians strongand sturdy but of doubtful ancestry, the latter are the aristocratic wealth-producing varietiesthat we rely on for food and increasingly for bioethanol. The US Energy Independence &Security Act, which was signed at the end of 2007, has set an ambitious target of 220billion litres (60 billion US gallons) of bioethanol to be produced annually by 2030. Alreadythere are more than six million cars on the roads in America which are able to run on E85,the fuel that is 85% ethanol and 15% gasoline, and more and more gas stations are nowproviding it – and not only in the Midwest where most of it is made. Production has beenhelped by allowing bioethanol plants to be governed by the same laws as distilleries andnot be classed as chemical plants with all the restrictions that implies.

Syngenta’s part in the drive to make the US less dependent on imported fuel is to makeUS maize more efficient and to require less water. That’s what John Arbuckle is workingto achieve and there are plenty of wild varieties of maize, technically referred to as ‘landraces’ from which to choose. Cultivated maize is having some of its alleles replaced bythose from older native strains. This approach is complementary to conventional genetic

modification in that it is not introducingalleles from different species into the genepool, but merely transferring from maizeto maize beneficial traits that have beenmissed down the centuries of selectivebreeding.

The initial list of 300 potential allelicdonors was narrowed down to 134based on the genotypic data using SSRs(simple sequence repeats) and genesequences. From these, 65 diverseinbreds and 69 individual representativesof land races were selected for platformdevelopment, based on moleculardistances as well as on the authoritative

There’s always a danger when the elite mate with the elite that their offspring lacksomething. Introducing tougher genes from peasant stock is what’s needed andthat’s what John Arbuckle is trying to achieve for maize, which is a major US sourceof food and bioethanol.

Time to introducesome new bloodinto the elite stockof maize (corn)



classification of races of corn publishedin 1988 by Major Goodman and WilliamBrown.

The key thing in the area of molecularmarker development and precisionbreeding is to take small segments ofDNA from land races and put them intothe elite breeding pool, without bringingother traits with it” is how John explains it.“Advances of the past 15 years havemade this possible.” Kinase, thephosphate transfer enzyme, is a case inpoint. In the current pool of cultivatedmaize there is much less than in the landraces. For one specific kinase typre

called the shaggy-like kinase, - we see 8alleles (variants) of this kinase in our elitegermplasm. However when we surveylandraces and non-elite material we findat least 10 additional variants of thisspecific kinase.

By breeding, we are re-introducing somekinases from landraces and non-elitematerial and some are indeed better thanthose in existing elite lines.

The domestication of maize started inMexico and then spread both north andsouth with native people selectingdifferent aspects to improve the crop fortheir own needs. In the US there wasparticularly strong selection and a lot ofthe genetic diversity of the wild specieswas lost. Maize has 10 chromosomesand there are centimorgan mapping unitsacross all these chromosomes giving atotal of 2,500 centimorgans. It is nowpossible to transfer a single centimorganfrom an exotic to an elite strain and testwhat effect it has.

Climate change is being felt in the USAwhere farmers are now having their waterfor irrigation rationed. They can offset thisto some extent by being more efficient inthe way that they use it. Maize can copewith drought but not at the critical time ofyear when the plant is in the juvenile andreproductive phase. No rain in thesecond half of July and a farmer standsto lose more than half his crop, threequarters in really bad times. A more

permanent solution would be to grow avariety of maize that is more droughttolerant. However, improving droughttolerance must not compromise otherbeneficial traits. Resistance to localdiseases and standability are also beinginvestigated. Without good standability acrop may be impossible to harvestbecause much of it is laying flat on theground.

This year Syngenta is testing acommercial line that contains targetedalleles from exotic germplasm thatconfers yield stability under droughtstress. “Such maize is the high profiletarget that we are aiming at” explainsJohn. Approaching old questions withnew ideas is how John sees things, inthis case bringing together allelic diversity,molecular markers, and genomics. “Iwant to get people thinking beyondtraditional breeding methods and to thinkin terms of these concepts.”

There is every indication that he and hiscolleagues will succeed.

The Syngenta Native Traits people involved

with John are S. Gandhi, , T. Williams, Aaron

Rasor, A. Josue, M. Li, N. Martin, V. Kishore, A.

Gutierrez, R. Bensen, C. Zinselmeier, H.

Caton, and Lynn Senior. The Syngenta

Molecular Marker researchers are K. Kust and

R. Burr. The Syngenta Applied Genomics

people are M. Dunn, S. Muncie, T. Zhu, C.

Chilcott, and J. Clarke

John Arbuckle went to college at Southern

Illinois at Carbondale and then to Illinois State

University where he learned all about corn

genetics before going to work as a molecular

geneticist at Pioneer Hybrid, now part of Du

Pont. In 1999 he joined Syngenta (then

Novartis) and was brought in to build up the

molecular marker section. In 2005 he was

given the opportunity to investigate native traits

and asked to build up the new group. He is

now head of the native traits corn and soya

section of the Traits and Technology Group

based at Stanton, Minnesota.


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Trevor Green, who recently retired from Syngenta after a distinguished career in

Investigative Toxicology, led a three-year project which solved the scientific puzzle of why

thiamethoxam could cause cancer in mice and yet not have the same effect on rats or

humans. The other team members were Timothy Pastoor, Alison Toghill, Robert Lee, Felix

Waechter, Edgar Weber, James Noakes, Mervyn Robinson, Sara Lloyd, Richard Peffer

and Patrick Rose. Together the group opened new doors for thiamethoxam. The

mechanistic research effort was undertaken to try and understand the human health

implications of the mouse liver effects, and to provide regulators with scientific data that

would allow them to move away from conservative default assumptions.

So impressed was the US Environmental Protection Agency (EPA) by the rigor of the

team’s research that it reclassified thiamethoxam as ‘not likely’ to be carcinogenic in

humans. This simple change in wording has a major positive impact for Syngenta, because

Toxicology teamensure that ants don't win


it has resulted in a much wider ability to

register and sell products containing

thiamethoxam in the US, Canada and in

other regions.

Thiamethoxam can cause liver cancer in

mice because of two metabolites. The

first of these, in which the methyl group

on nitrogen has been lost (CGA330050),

affects cholesterol biosynthesis and

causes mild liver dysfunction, which

appears within 10 weeks. Decreased

cholesterol level in plasma was one of the

Thiamethoxam is a broad spectrum insecticide ideal for use against crop pests, turfpests, and ants. However, this new insecticide was initially classified by the EPA as a‘likely’ human carcinogen. Today it is rated as ‘not likely’ thanks to world class researchby a dedicated Toxicology Team – as Richard Peffer (Senior Toxicologist, Greensboro)explains.

08


earliest effects of thiamethoxam in mice,

and it did not occur in rats. A second

metabolite (CGA265307), in which ring

opening has occurred, inhibits the

enzyme iNOS (inducible nitric oxide

synthetase).

Trevor Green noted the structural

similarity of the major mouse metabolite

CGA265307 to known inhibitors of iNOS,

and this insight led the team to do

specific in vitro experiments that

demonstrated its potency for inhibiting

this regulatory enzyme. When iNOS is

inhibited, it no longer signals a cell to turn

off the normal process that removes

damaged cells (apoptosis), and so mild

liver dysfunction spreads to become

more pronounced liver damage. In

response to the hepatotoxicity, which can

be seen as increased necrosis of cells by

20 weeks, cell proliferation accelerates as

the liver tries to replace damaged cells

and maintain normal function. The rapid

rate of cell division enhances the chance

of a spontaneous mutation occurring and

of these transformed cells surviving in

liver tissue. This results in an increase in

mouse liver tumors after more than one

year of high-dose treatment.

A second critical revelation from the

team’s research is that species

differences in metabolism produce

differences in effects. In rats and humans

the same metabolites form as in mice,

but in such small quantities that liver

dysfunction and other changes that lead

to cancer do not occur. A different

metabolic pathway is more dominant in

rats and humans, as illustrated in the

figures below. The team even

demonstrated that CGA265307

treatment of mice for up to 20 weeks by

itself did not produce the liver damage

that occurs in mice with thiamethoxam; it

took the 1-2 punch of both CGA330050

and CGA265307 to generate the mouse

liver effects.


Team member Tim Pastoor, Principal

Science Advisor in Greensboro, had

earlier participated in an ILSI (International

Life Sciences Institute) work group drawn

from industry, academia, and

government, which provided a road-map

or “framework” on how to evaluate

animal mode-of-action data and its

relevance to humans. In 2003 the group

published its framework document (Meek

et al., 2003) which is now in use by the

EPA, academic, and industry

researchers. This framework document

provided the lens through which some

highly detailed biochemistry could be

viewed and evaluated.

The mode-of-action data for

thiamethoxam produced by Trevor Green

and the research team fit into this new

framework just like a hand into a glove.

Syngenta has always set the bar high in

terms of the level of science needed to

understand what’s happening with our

products. This has allowed us to provide

the EPA with the scientific certainty to

move away from restrictive assumptions

about our products, while establishing us

as a leader in the areas of investigative

toxicology and mode-of-action research.

The thiamethoxam mode-of-action work

was carried out in the in the UK at the

Central Toxicology Laboratory at Alderley

Park, in Switzerland at the Biochemical

Toxicology section in Basel and in the

USA in the Human Safety Group at

Greensboro. This group’s novel results

with thiamethoxam, and their use of the

ILSI Framework to critically evaluate the

mode-of-action and its relevance to

humans, can be read in three landmark

papers in the journal Toxicological

Sciences published in 2005. As a final

icing on the cake, the team won the

prestigious "Best Paper" award from the

Society of Toxicology for this series of

papers, chosen from a list of 300

nominated papers!

If you’d like to know more about the

group’s research consult the following

papers:

Trevor Green, Alison Toghill, Robert Lee,

Felix Waechter, Edgar Weber, and James

Noakes, ‘Thiamethoxam induced mouse

liver tumors and their relevance to

humans. Part 1: Mode of action studies in

the mouse’, Tox. Sci. 86, 36-47 (2005).

Trevor Green, Alison Toghill, Robert Lee,

Felix Waechter, Edgar Weber, Richard

Peffer, James Noakes, and Mervyn

Robinson. ‘Thiamethoxam induced

mouse liver tumors and their relevance to

humans. Part 2: Species differences in

response’, Tox. Sci. 86, 48-55 (2005).

Timothy Pastoor, Patrick Rose, Sara

Lloyd, Richard Peffer, and Trevor Green,

‘Case Study: Weight of evidence

evaluation of the human health relevance

of thiamethoxam-related mouse liver

tumors’, Tox. Sci. 86, 56-60 (2005)

Meek,M.E., Bucher, J.R., Cohen, S.M.,

Dellarco, V., Hill, R.N., Lehman-

McKeeman, L.D. , Longfellow, D.,

Pastoor, T., Seed, J., and Patton, D.E., ‘A

Framework for Human Relevance

Analysis of Information on Carcinogenic

Modes of Action’, Critical Revs in

Toxicology, 33, 591-653 (2003).

sm

09


Klaus Gehmann is a man with a mission: to make every field trial count. Achieving itwould ensure Syngenta seeing the successful launch of more new products in the yearsahead. Klaus also seeks to achieve an equally challenging objective: for Syngenta tooutperform its competitors and be nothing less that the best.

It’s Klaus’s job to oversee the technical development of new products and this involves field

studies. Syngenta carries out more than 10,000 trials every year and there are so many

variables that unless there is total control, the findings could be irrelevant. The ideal is to

produce the technical profile of a particular product, ensure it delivers what the customer

requires, and ultimately to gain a competitive advantage for Syngenta. Recent successes

include the fruit and vegetable fungicide mandipropamid sold under the brand name of

Revus®, the cereal herbicide pinoxaden (Axial®), and the broad spectrum insecticide

chlorantraniliprole (Durivo™). This last one has been developed in co-operation with DuPont.

These innovations followed from a relationship between Syngenta and the growers and

were successful because of the close interaction between the two. Klaus: “Closing the

loop from the market to Research & Development is of utmost importance for successful

innovations delivering value to the

customer. This is our role in Global

Product Biology. However, we would fail

miserably without competent field

scientists who are in the middle of the

grower and influencer communities, and

who sense the opportunities.”

Indeed the scientists responsible for the

field tests are the key players in the game

and the success of Syngenta's technical

development rests on their skills. It is up


Product Biology:

the sun neversets on Syngentafield trials


to them to perform the tests correctly and

to capture the data coming from them.

The field scientists need to know the

agricultural crops and their agronomics,

and understand the biology of the target

organisms. They need to be experts in

trial design and application technology,

know how to assess crop tolerance,

biological efficacy, and yield. And of

course it is the last of these which is the

main concern of the farmer.

Klaus: “We are proud tohave a superb field force inour key countries. Theyknow how to make ithappen and have the‘can-do’ attitude whichmakes all the difference.Experienced colleaguestrain newcomers from newgrowth markets such asIndia, China and Russia.”

Although the field trials are important they

also depend very much on their careful

planning beforehand and on the

gathering and processing of data when

they have been completed. There are

four interlinked phases that Global

Product Biology sees as the key to

successful field trials: (1) upfront planning;

(2) conducting the trials; (3) analysing and

documenting the experimental results;

and (4) sharing the information and

building corporate knowledge.

Even the best field work will be valueless

if the trial protocol or the experimental

product samples arrive too late so that it

is not possible to conduct the trial at the

most appropriate time. Also any trial

whose results are not properly analysed

is a wasted trial because it does not add

to the Syngenta pool of knowledge.

At the planning stage one obvious piece

of information to be aware of is whether

something has already been tested.

There is little to be gained by retesting

product concepts which have already

failed in the past – and that’s why the

corporate archive – or as Klaus puts it

‘corporate memory’– is so important. The

field scientists capture the data with

hand-held mini-computers while actually

in the experimental plots. This information

is then uploaded to the global database

at Basel where it can be analysed within

a few days by Syngenta staff around the

globe. This may be critical to gaining

competitive advantage because speed

really can matter. Finally comes the all-

important phase of drawing the right

conclusions, documenting them, making

recommendations, and elaborating the

various options for marketing.

Klaus: “Our field resource is precious and

an asset to Syngenta. To maintain its high

quality it must not be overloaded with

unnecessary work. All of our technical

development needs to work seamlessly

together. Most recent successes show

that we are well positioned, but we must

do even better, and to continue to keep

ahead of our competitors”

Planning field tests definitely requires a

global perspective because it

encompasses both the Northern and

Southern hemispheres. The sun literally

never sets on Syngenta field trials.

Klaus Gehmann joined Ciba-Geigy in

1987. He had trained as an agrobiologist

and did his PhD in Agricultural Sciences

at the University of Stuttgart-Hohenheim,

Germany, specialising in crop protection

for vines. In 1996 Klaus moved to Brazil

as Head of R&D. In 2002 he became

Head of Global Product Biology, and is

based in Basel, Switzerland.


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Marc Moerkerken holds a management position in the Global Supply Cjain Flowersand is based at a remarkable facility at De Lier in The Netherlands. There theplanting, germinating, and transplanting of flowers has been automated, and itsbusiness has grown by 10% per year for the past 10 years. Their secret weapon isthe Xtray®.

What Syngenta did in 1999 was to revolutionise the industry by introducing the Xtray®,

thereby not only introducing automation but also increasing efficiency, and it came with

environmental benefits. In place of traditional seed trays, which were used only once and

then discarded, Syngenta now has returnable plastic trays made of polypropylene which

will last for ten years. Instead of the previous ten types of tray there are now only four

types, with between 72 and 480 compartments (cells), and all are of a standard size of 30

x 50 cm. Every Xtray® has a unique number. This is in the form of a bar code which is

scanned in at the distribution center and scanned out when the tray is returned and

cleaned for re-use.

Leo Eland is the process engineer in Marc’s team and a key player in developing the Xtray.

These were designed to be strong and be unaffected by UV. Each tray will on average be

sent out once or twice a year. Customers

return them to Syngenta where they are

cleaned and disinfected with a hydrogen

peroxide solution, to remove all

pathogens before being used again. The

company has around two million Xtrays

in total and they ship out three and a half

million trays a year containing around one

billion plants.

Part of the company is a purpose-built

distribution facility at Maasland, a few


A bouquetfor De Lier


kilometres south of De Lier. This was

opened in 2005 and its manager is Ron

Koene. Marc: “Ron did a magnificent job

when this was set up and the challenge

was to relocate the distribution operation

from De Lier without jeopardising

customer deliveries. Thanks to Ron and

his team the move went without a hitch

and all within the regulations laid down by

The Netherlands government and the

local municipality.”

As you might expect, young plants

production is a very seasonable business

and the company has to rent greenhouse

space at the peak time of year, and

indeed 80% of the plants they are

producing are then located off-site. From

the production sites the Xtrays are taken

to the distribution centre.

Within the Syngenta main plant, the filling

and sowing are fully automated and there

are six production lines. After sowing, the

Xtrays go to the greenhouse or are

stacked in a climate chamber. (The trays

have been designed for stacking and are

strong enough to bear the weight.) This

stacking is again another benefit over the

older system because it saves so much

space. The trays are left for up to a week

for the seeds to germinate. After that

they are further grown on in the

glasshouse. They are then inspected to

see how successful the germination has

been. This is also fully automated and is

done by counting the number of green

pixels the machine detects on its image

of the cell. Plugs which fail to meet the

grade are replaced. A second process is

to transplant the seedlings to larger cells

and again this is automated.

Marc: “We had some teething problems

with the machine because we were one

of the first companies to adopt this

technology. In fact it is a three-in-one

machine that combines transplanting,

gapping and sorting, which makes it very

versatile. It can also accommodate

certain products (mainly begonias and

cyclamens) that were not suitable via the

automatic gapping lines because those

products have leaves which may bend

over on to an adjacent cell of the Xtray®.

The counting machine would then

register that cell as the one that has

successfully germinated and the cell

which has the successful plant would be

rejected.”

As befits its position as the world’s

leading flower producer, Syngenta is

gearing itself up to be a ‘lean’ player,

producing the highest quality young

plants in the most efficient manufacturing

plant in Europe. Thanks to the invention

of the Xtray® it has greatly reduced the

amount of waste packaging that was

previously needed to supply the many

businesses it serves. Next Spring when

you are buying a magnificent pansy –

which is when most of these plants are

sold – then say a prayer of thanks for the

wise men of De Lier.

Marc Moerkerken completed a degree in

business administration at the Erasmus

University Rotterdam in 1998, after which

he became a supply chain consultant

before joining Syngenta in 2003 as

project manager for the Young Plants

Supply Chain. In early 2004 he was

promoted to the Global Supply Chain

(Flowers) and later that year to his current

position in the company which is now the

world leader in the flower industry. That

came as a result of Syngenta buying

Fischer Flowers, which specialises in

geraniums and poinsettias. The

combined company now supplies more

than 3,000 genetic varieties of plant, and

it’s Marc’s job to see that the merger

blooms into a successful hybrid.


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Steve Goff’soff to Arizona



Steve did his PhD in molecular genetics

at Harvard in 1985, then worked with

Biogen S.A. Geneva, before moving to

Tuft’s Medical School. He switched his

research focus in 1987 to gene

expression in plants at the Plant Gene

Expression Center at the USDA and

University of California Berkeley.

Steve was awarded“Research Leader of theYear” by ScientificAmerican in 2002 for hiswork on sequencing thegenome of rice, whichwas the first crop plant tobe sequenced.

He was also very interested in human

flavour perception and he has written 50

original research papers and filed even

more patents. In 2003 when Syngenta’s

Torrey Mesa Research Institute (TMRI) in

San Diego closed, Steve moved to

Syngenta Biotechnology Inc (SBI), North

Carolina, to become a Senior Syngenta

Fellow. His group’s efforts were focussed

on the science at the intersection of plant

and animal biology. In the August 2004

issue of Scientific American, he co-

authored the cover article with John

Salmeron entitled “Back to the Future for

Cereals.”

Now Steve has a faculty position at the

University of Arizona as the Director of

Community Interactions for the NSF-

funded iPlant Collaborative. The $50

million project is designed to develop

computational tools and cyber-

infrastructure to solve the major research

problems in plant biology – the so-called

Grand Challenges.

“Steve’s new position will give us insights

into how Syngenta can collaborate and

benefit from the exciting advances being

made at the University of Arizona and the

broader NSF initiative with which it is

associated.” says Martin Clough, Head of

Biotechnology R&D.

Steve gave a farewelllecture on 29 April 2008 atthe SBI Science Forum.His talk was entitled‘Recent Learnings fromGenomics: What we’velearned about genes andwhat opportunities theselearnings create.’

During it he reviewed recent literature

findings and discussed why it is so

difficult to associate genes and the traits

they cause. He went on to describe

some recent developments in genomics

and plant science that will impact

Syngenta's delivery of both Transgenics

and Native Traits products, and will be of

interest to the scientists trying to

understand the mode-of-action of

Syngenta's chemical products.

After his lecture, Steve was joined by his

co-workers in a celebration of his

contributions to Syngenta and his 16 year

tenure with the company. Erik Legg,

Group Leader for Integrated Genome

Biology, paid tribute to his work: “While I

am sad that we are losing Steve and his

ability to consolidate data, ideas, and

thoughts, we will continue to strengthen

our relationship with public sector

scientists through him. Syngenta will

continue to offer support which facilitates

the interaction and collaboration between

our company and academics.”

Steve was clearly moved: “I'd like to

thank you all for the exciting years at

Ciba, Novartis, TMRI, and finally back at

SBI. It's been a wonderful learning

experience, and I have had opportunities

to interact with a lot of very bright people

with widely different perspectives. I wish

you all the best of luck for the future, and

I'd be happy to host your visit to the BIO5

Institute at the University of Arizona in the

next five to ten years. We'll be working on

software for plant genomics and

addressing the Grand Challenge

questions in Plant Sciences. Some of

these should be very useful for

companies like Syngenta, and I hope to

be able to come back and describe

progress on this NSF-funded effort in the

future.”

Readers who would like to contact Steve

can reach him at his personal e-mail

address [email protected] or at

Arizona [email protected] and it

you’d like to read his last seminar you can

download it from the Syngenta database.


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On 30 April 2008, and after 16 years at Syngenta, Senior Fellow Steve Goff retiredto take up a faculty position at the University of Arizona. During his remarkableresearch career Steve made some ground-breaking contributions to the science offlavour and plant genomics.


When it comes to pathogenic diseases nothing exceeds malaria both in the number ofcases every year and the numbers who die. Syngenta is playing an active role in fightingback, thanks to a rather neat way we have discovered of making bed nets much moreeffective.

It’s the job of those in the Formulation Development Section to take the raw activeingredients such as fungicides, herbicides or insecticides which are made by the syntheticchemists and turn them into the products that people can use. And it’s not only bulkpurchasers who are their customers, some buy Syngenta products for personal protection,and that’s what Icon®Maxx is all about.

Malaria is probably the world’s worst killer disease andthe World Health Organisation (WHO) estimates that 300million people a year suffer from it.

Every day the number of children actuallydying from malaria would fill seven jumbojets, such is the terrible toll this diseasetakes.

Lesley Silverthorne’s project was todesign an insecticide which could beapplied to mosquito bed nets to providelong-lasting protection against theseinsects. Previous products of this typetended to be washed off when the bednet was laundered and people would


Seven jumbo jet loads of children crash into

mosquitoesevery day


then forget to reapply more. Thechallenge that Lesley’s team faced wasto devise a formulation which was wash-fast, which retained its activity for longperiods, and which was easy to apply bythose who purchased the insecticidal kit,or who were given it by their governmentor aid agency along with a bed net.

Lesley: “We provide Icon®Maxx userswith an outer bag into which they canmeasure the correct volume of water andinto which they then dilute the Icon®Maxxbefore immersing their bed net andsoaking it for at least 30 minutes. It canthen simply be left to air dry and this issufficient to allow the binder to stick thecapsules to the netting.”

So how long does an application have tolast? Lesley: “A typical net would last thehouseholder for up to three years. Duringthis time they can wash the net if itbecomes dirty but the capsules willremain attached even if the nets arewashed with the aid of a detergent.” TheWHO has approved Icon®Maxx afterbed nets treated with it successfullypassed their test of still being active after20 washes. Competitor products failed tosurvive this stringent test.

The challenge was to find a way ofbonding the insecticide to the net butensuring release of the insecticide in a

controlled manner. Lesley: “This was aparticularly tricky challenge. If you boundthe active ingredient too tightly to the netyou could lose the knock-down effect.”

The answer was toencapsulate theinsecticide in a polyureashell and then stick theminute capsule to the bednet fibres with a binder.

In the research phase Syngenta scientistsin the UK and Switzerland looked at morethan 60 binders and various bed netfibres including nylon and cotton. Theformulation chemistry was done atJealott’s Hill, UK, by David Barnett andBeverley Mason, and the biologicaltesting was done at Stein, Switzerland,by Andy Bywater. The aim was tobalance insecticide release with long termactivity and an ability to survive laundering– and they did it.The capsules are formed byincorporating isocyanate precursors,polyphenyl isocyanate and toluenediisocyante, into an emulsion systemcontaining the insecticide within the oilphase. The isocyanates react first withwater at the emulsion droplet surfaceforming amino groups which then go onthe react with other isocyanate groups togenerate polyurea linkages, effectivelycreating a shell around the capsule withthe insecticide inside.

The attachment of these minute capsulesto the net fibres is a more physicalbonding process. The binder is basicallyan ethyl vinyl acetate film-formingcopolymer. The key is to use the rightpolymer at a specific rate to ensure thattreated nets can be simply air driedwithout the need for curing with theresulting treatment being wash fast andthe capsule contents are still bioavailable.

The active agent inIcon®Maxx is λ(lambda)-cyhalothrin (a fluorinatedpyrethrin) which is a veryeffective insecticide andso application rates canbe kept low.

Cyhalothrin is active at a very low leveland there need only be 50 mg per squaremetre of the net to be effective againstmosquitoes. Tests were also carried outto show that even if a child chewed itsmosquito net then its health would not beat risk.

Now, after her maternity leave, Lesley hasreturned to the Formulation DevelopmentSection at Jealott’s Hill to work on newproducts. Needless to say she has fittedher babyAmelia’s pramwith amosquito net.

Lesley Silverthorne has a degree inchemistry and is a graduate of the RoyalSociety of Chemistry. She joined ICI atJealott’s Hill in 1987, relocated to Kent for10 years and then returned to Jealott’sHill in 2002 as a member of theFormulation Development Section, whichis headed by David Sadler. It’s there thatshe and her team have waged waragainst diseases like malaria by forging anew weapon to defeat mosquitoes:Icon®Maxx. This was launched at the endof 2007 and sales are already exceedingexpectations.


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When a weed shows resistance to an important herbicide, Syngenta’s dedicatedlabs employ a wide variety of latest technologies to discover the secret of itsdefence. Better ways can then be found to defeat resistance so that it is containedand food production is not threatened.


a real threat for agriculture but an opportunity for Syngenta!


Herbicide resistance weeds are a serious

threat to agriculture and food production.

Syngenta was quick to recognize this and

has invested significantly in better

understanding and managing resistance.

Scientists from the resistance research

team at Jealott's Hill have developed an

array of scientific methods for uncovering

the mechanisms by which weeds eveolve

resistance. These have lead to the

development of new techniques to detect

resistance in the field. Using their

scientific results they have empowered

the technical and sales team to manage

resistance in a competitive manner.

Deepak Kaundun did his PhD in

biochemistry at the University of Lyon,

France, followed by further research at

public institutions in France, South Korea

and Japan, before coming to Jealott’s Hill

in 2002 as their technical specialist in

charge of herbicide-resistance. His

colleague, molecular biologist Richard

Dale, did his degree in genetics at Leeds

University, UK, before joining Syngenta’s

Bioscience Department.

They are members of a remarkable team

with skills across diverse areas of

science, dedicated to finding ways to

attack the forces of herbicide-resistant

weeds which march across the fields of

the world’s key grain crops. They are really

making a difference in understanding and

combating resistance thanks to what

Deepak calls their holistic approach,

which brings together the science of

biology (both field and glasshouse),

biochemistry; molecular biology,

physiology, biokinetics, genomics and

genetics (both quantitative and

population). Deepak views herbicide

resistance as a real opportunity rather

than a threat for Syngenta. “We can

leverage the sophisticated technological

platforms across the company for a

better understanding of herbicide

resistance and have a wide portfolio of

herbicides that can be used for delaying

and overcoming resistance.”

Resistance is a fact of life. It occurs

worldwide where herbicides have been

used extensively. For example in Australia

it’s rye grass and in the UK there is black

grass. These and other weeds have

evolved to become resistant. Lack of

diversity in farming methods and overuse

of previously highly effective herbicides

have allowed plants with a slightly

different segment of their genome to

survive. Thereafter their progeny will

cross and further spread across and to

adjoining fields.

So what happens when afarmer discovers a weedthat has survived aherbicide treatment inhis field?

The first step is for seeds from the

suspect plants to be collected and sent

for resistance confirmation under

controlled glasshouse conditions at

Jealott’s Hill. This has to be done

because the weeds might just have

survived due to sub-optimal spraying

conditions in the field. However, if the

plants remain healthy the next step is to

develop a solution based on mixtures

and sequences of existing herbicides.

Simultaneously Richard will take a

sample of leaf and extract the DNA. He

then compares its gene sequence with

the DNA of a known herbicide-sensitive

plant and finds where it differs. Very often

the difference should point to the cause

of resistance.

DNA based methods arethen developed for theearly and unambiguousdetection of resistance,thus limiting its spread inthe field.

Thanks to their deep understanding of

herbicide resistance mechanisms they

have generated some unique weed lines

for screening new herbicides in research

that would overcome resistance.

The group’s work is also of the highest

scientific calibre and has been published

in peer-reviewed international journals.

Their robust and unambiguous DNA

based methods for the early detection of

herbicide resistance are used by both

Syngenta scientists and by academic

collaborators worldwide.

Deepak: “I see myself as the link between

the scientists at Syngenta and the

growers. We make sure that each and

every one of our experiments is designed

for the mutual benefits of Syngenta and

its customers. Once we have confirmed

resistance in a weed and understand its

mechanism we are in a better position

once again to protect crops. In so doing

we can demonstrate Syngenta’s

capabilities in a competitively

advantageous way.”

As Iain Hamilton, Field Technical

Manager, indicates: “Scientific support

was of significant help in the launch of

Axial® on the UK market, demonstrating

to potential clients that this was a

herbicide that was different from those of

our competitors. We have the ability to

give advice and support to growers and

advisers about how to tackle difficult

grass weeds in the field and that’s a real

bonus for us.”


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Ashley Collins, based at Syngenta Biotechnology Inc., North Carolina, reports on oneof the highlights of the Syngenta Year.


SyngentaFellows AnnualConference 2008


The Fellows’ Annual Conference was

held in April in Zurich, Switzerland and

included a colloquium devoted to Applied

Crop Enhancement (ACE) which was

held at the Syngenta site at Stein. The

focus was on improving networks, both

internally and externally, the better to

drive technology and scientific progress

within the company.

“With technicalleadership, know-howand expertise, theFellows aim to influencethe future of theirfunctions and overallbusiness”, explainedDavid Jackson, FellowsCore Team Member.

The ACE colloquium saw a full program

of speakers, themed workshops, and the

awarding of science prizes, all of which

combined to create an atmosphere of

sharing, brainstorming, and celebration

for the 80 participants.

Lynn Senior, SBI-based program leader

for yield and yield components, kicked off

the day’s lectures. Her talk, which

focused on how to better characterise

the vigour effect of thiamethoxam using

a combination of genetics and genomics,

set the theme for the day which was

devoted to the linkage of classical

genetics with chemical genetics. Lynn’s

lecture was followed by several external

speakers from local universities including

Ghent University, The Free University of

Berlin, The Max Planck Institute for Plant

Breeding of Cologne, and ETH Zurich.

“It has been great to see that the link

between seeds and crop protection has

been reiterated through the scientific data

presented by both our internal and

external speakers,” said David Lawrence,

Head of Global Research and

Development. “Syngenta now has the

challenge to utilise the potential of the

ACE program to deliver solutions to our

customers.”

After lunch there was a brief question and

answer session, and later the attendees

divided into small groups focusing on

idea generation in five key areas for ACE

improvement. These areas included:

vigour; maturity management; soil

nutrients; abiotic stress; and quality

enhancement. Each group narrowed

their suggestions and ideas for the next

steps down to five; and shared their

findings with the group in a plenary

session. The ACE group, with Fellows

involvement, will now deep dive into the

findings and identify projects of most

interest to Syngenta.

The Colloquium also saw the

presentation of awards to the 2007

Science and Technology Prize winners.

David Lawrence praised the three

recipients: Gabriel Scalliet and Olivier

Loiseleur of Stein, and Judith Bowler of

Jealott’s Hill. Each winner delivered a

summary of their work.

Gabriel: “It is veryrewarding to get thisprize because it showsthat science makes adifference to thecompany. Innovationmakes a difference.”

The next day, the Fellows spent time at

ETH, Switzerland’s top university, to

strengthen their co-operation and

networks, and to hear presentations from

professors and researchers. Pat

Mulqueen, Senior Syngenta Fellow and

2007 Core Team Chairman, was

particularly impressed: “The visit to ETH

allowed us to meet key researchers. For

me, the particularly exciting talks were by

Professor Starke on nanoparticle

technology (using inorganics such as

calcium phosphate as a model) and

Professor Seeburger and his students

about precisely constructed polymeric

sugars in defining adhesion to

substrates.”

The Fellows spent the final day learning

how to better understand the importance

of networking. External consultant, Ray

Smith, laid out the foundations of

effective networking: mutual trust, mutual

objectives and mutual interests. In small

group sessions the Fellows focused on

their main areas of improvement for this

year which they identified as networking,

behaviour, brand and innovation.

“The Fellows communityhas been given challengesto deliver more throughnetworking acrosstechnical and businesssilos” says Mike Bushell,head of ExternalPartnerships at Jealott’s Hill.

“A pilot training and development

program is being developed around the

Technology Foresight networks on

Epigenetics and Measurement, and

Modelling, assisted by Ray Smith and his

New Game Plan group. If it is successful,

more projects could follow.”


sm


Our intrepid reporters, Carolyn Riches and Ashley Collins have been trackingdown some more interesting things which Syngenta people have been involved in.With thanks to Sirku Ploetner.


Out and About

Gowith the flow-reactor“Upgrading the H-Cube to link with aredundant liquid handler is a major leapforward!” exclaims Gavin Bluck, Jealott’sHill Research Chemist. The H-Cube is akey piece of technology for performinghydrogenation reactions. Using a flow-reactor, it generates its own H2 in situ byelectrolysis of water. “We’ve discoveredand optimised conditions for reactionsthat weren’t successful by 'conventional'methodology.”

The unit is able to perform multiple small-scale (i.e. less than 0.5 mmol) reactionsunattended which he says is great forrapidly investigating optimal conditionsand it frees up time for other tasks - oreven coffee!

Flexibility has been maintained to copewith large-scale field-trial syntheses. Onthe day that Gavin first plumbed the H-

Cube into the liquid handler, he had arequest to hydrogenate several litres of akey intermediate. “Within a couple ofminutes, I‘d transformed the unit intobeing able to cope with large-scaleprocess work…and then I was off!” saysGavin.

Global‘webinars’captureReach-outenergyHow can you disseminate information onimportant Syngenta projects to interestedglobal parties, and at the same timecapture their ideas? A ‘Reach-out’ eventis the answer. Franz Doppmann and hisDevelopment team have harnessedinternet seminar (or ‘webinar’) technologyto enable live internet broadcasting. Anynumber of people can join the ‘giant net-meeting’ via their PC and phone. At theend of the broadcast a Q&A takes place,with global participants posing questionsvia e-mail or over the phone. A follow-upReach-out event captures thoughts,ideas and energy while still fresh in themind. Attendees may also spend acouple of daysworking on issues that arose.

Jealott’s Hill Weed Control Group Leader,Mark Spinney, is clearly impressed: “Frommy desk, I’ve connected with both SeniorManagement and the span of our globalorganisation, as well as gaining criticalinformation about some of our mostexciting new products, such as Invinsa®.”

Webinars now feature regularly and areopen to all employees in Syngenta R&D.For more information on when these willtake place, put the link below into

mySyngneta or contact Cornelia Maier.http://ts1.pro.intra/sites/GCPDCentralR/Development%20Conference%20Library/Forms/By%20Linked%20Event.aspx

Employee exchange is a ‘Goa’Goa Team Leader, Mangala Govenkar,has completed her nine weeksecondment to Jealott’s Hill/Stein as partof a training programme for chemists.Mangala immersed herself in a researchproject, having hands-on experience inthe labs and greenhouses – somethingno amount of teleconferences and e-mails could offer. “I’ve enjoyed thechemistry discussions and meeting alarge number of scientists across alldisciplines,” says Mangala.

Such exchanges have proven invaluablein linking colleagues in Europe and Goa.“It was good for us to build a relationshipwith a key project member,” says Chris


Mathews, Group Leader (JH). “This willenhance her team’s ability to work moreeffectively, encouraging still greater inputinto this and future projects.”Secondments for Goa employees haveprimarily been for those needing closeinvolvement with projects - furthersecondments to Stein are planned fortwo more Goa Chemistry Team Leaders.

Also this year, a Jealott’s Hill / Steinexchange took place between OlivierProvoost and Mario Juerg. Chemists’self-nominated and candidates wereselected by their managers. Rob Lind,Team Leader, Bioscience (Jealott’s Hill)has also completed a secondment inStein. If you’d like to take part in anemployee exchange, your line managercan provide guidance.

In a flash…Ultra Thin Client (UTC) technology isgoing on a two month trial at Jealott’s Hillfrom June. A UTC is like having your PCin your pocket and the ability to log-onwherever you happen to be on site. Thescientists trialling the technology will beable to immediately log-on to a centralserver by inserting an access card into abox next to a monitor. The screen isrecalled exactly as when they were lastlogged-on - instant working, in a flash!

The Discovery Biology Group and twoproject teams will be trialling the UTCs.With monitors taking up less desk space,office layouts have been designed forinteraction and space efficiency. This fitswith the project room way of workingalready in place at Jealott’s Hill: key

project members temporarily locate inone room, ‘hot desks’ are available forperipheral members and informal coffeesessions enhance the flow of new ideas.Jim Mills, Jealott’s Hill Biology Technician:“Having a base in several buildings, I’mlooking forward to being able to log-onstraight away”. For more information,contact Derek Scuffell, UTC Project Lead.

It’s good to talk…"The Stein Interaction Centre has alreadyinfluenced our ways of working bycreating numerous spontaneousopportunities for networking andknowledge sharing,” says Mafalda Nina,Research Computational Chemist (Stein)speaking of the new facilities at our Swiss

research site. Syngenta officially openedthe Interaction Centre on April 10th,thereby reinforcing Stein's position asone of five main Syngenta research sitesworldwide, specializing in fungicides andinsecticides.

High-quality materials, lots of natural lightand the well-planned integration of open-air and indoor areas all contribute to anatmosphere ideally suited to innovation.It has also enabled chance interactionswhere colleagues from Biology,Chemistry and Patents often discussproject details outside of formalmeetings. “These opportune momentshave enabled me to quickly answerquestions with my Biology colleagues,saving time in making phone calls andemailing,” continues Mafalda.

The Interaction Centre with its auditorium,meeting rooms and offices also providesa fine location for scientific exchange andcelebrations (internal and external).Upcoming events planned for the Centreinclude visits from UK distributors, Swissagronomy advisors and Syngenta Salesand Marketing.

Hoorah for Project FuwaProgress of the Syngenta Biotech ChinaSite (SBC), known as ‘Project Fuwa’, is infull swing. With the Land PurchaseAgreement signed on April 10th, SBC islooking forward to what the future 21,500m2 building will add to Syngenta’sResearch and Development program.

Currently, SBC is run in a leased facility. InSeptember of this year, temporarylaboratory spaces will be set up andready to use. Additionally, recent campusrecruiting events have proven to be verysuccessful. For the fifteen open positions,over 800 resumes were received.“Syngenta is creating a very positiveimage of itself. We’ve been able to deliver

the message that we’re committed inChina. People like Syngenta, and want towork for Syngenta”, says Liang Shi,Group Leader for the Transformation andAnalysis Group. “It’s our hope that SBCand SBI will become closely connected.We hope to foster an open culture andgood collaboration between the sites.”

Mini-Chromosomes Could YieldMega ResultsThrough the partnership of Syngenta andChromatin Inc., we are now able to testChromatin’s gene stacking technology of“mini-chromosomes”. Mini-Chromosomesare developed using select elements froma crop’s existing chromosomes, includingthe centromere, which provides geneticstability and can help to ensureinheritance of the mini-chromosome. Thistechnology can offer Syngenta a newway to develop stacked traits and speedthe time from development tocommercialisation. While this newtechnology is very exciting for Syngenta,it will not replace our current methods:molecular stacking or traditionalbreeding. “We will evaluate thistechnology in combination with our owninnovative research programs. Mini-Chromosomes will give us the ability toenhance our product speed to themarket and potentially increase thenumber of traits that can be stacked intoone variety” says Roger Kemble, Head ofCrop Genetics Research.


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Writer John Emsley is author of several popular science books which deal with

everyday chemicals including TheConsumer’s GoodChemical Guide, whichwon the

Science Book Prize in 1995 and this has been translated in all major languages. His

latest book in the series is Better Looking, Better Living, Better Loving published by

Wiley-VCH.

Editor-in-Chief: Dr Dave Lawrence

Editors: Dr. Stuart John Dunbar, Dr Alison Craig

Written by Dr John Emsley

Printed by Geerings Print Limited

ScienceMatters is publishedbySyngenta, Jealott’sHill International ResearchCentre,

Bracknell, Berkshire, RG42 6EY United Kingdom. Main contact for comment and

future content is Mike Bushell.

Trademarks indicated thus ® or TM are the property of a Syngenta Group Company.

The Syngenta wordmark is a trademark of Syngenta International AG

© Syngenta International AG, 2008. All rights reserved.

Editorial completion May 2008.

Science Matters is printed on 9lives80 which is produced with 80 percent recovered

fiber comprising 10 percent packagingwaste, 10 percent bestwhitewaste, 60 percent

de-inkedwaste fiber and only 20 percent virgin totally chlorine free fiber sourced from

sustainable forests.

Cautionary statement regarding forward-looking statementsThis document contains forward-looking statements,which canbe identified by terminology such as “expect”,“would”, “will”, “potential”, “plans”, “prospects”, “estimated”, “aiming”, “on track”, and similar expressions.Such statementsmay be subject to risks and uncertainties that could cause actual results to differ materiallyfrom these statements. We refer you to Syngenta’s publicly available filings with the US Securities andExchange Commission for information about these and other risks and uncertainties. Syngenta assumes noobligation to update forward looking statements to reflect actual results, changed assumptions or otherfactors. This document does not constitute, or form part of, any offer or invitation to sell or issue, or anysolicitation of any offer, to purchase or subscribe for any ordinary shares in Syngenta AG, or Syngenta ADSs,nor shall it form the basis of, or be relied on in connection with, any contract therefore



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