Science Matters : Summer 2008

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matters

science Keeping abreast of Syngenta R&D

The A to Z of field tests Apples are just one crop tested by our global field testing team

From weevils to weeds, Biokinetics is revealing the effects of our products Syngenta scientists are introducing new blood into the elite stock of maize Thanks to a dedicated Toxicology team, Thiamethoxam is now able to fight pests From flowers to mosquitoes, to herbicide resistance, read how Syngenta scientists are achieving great things

Summer 08

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

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Our science has never been more important Contents Biokinetics: it’s the weevil’s knees of a problem

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Time to introduce some new blood into the elite stock of maize (corn)

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Toxicology team ensure that ants don't win

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

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

The food price crisis has been described as a wake up call to the world by Josette Sheeran, the head of the UN World Food Program. There is growing appreciation of the importance 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 is for farmers to become productive…any thinking environmentalist would want to see more intensification of agriculture.” While this is a really positive contribution to the debate, I am sure that not everyone shares this view. It does reflect their analysis of how to protect as many of the wilderness areas and rainforests as possible while rising to the challenge of doubling agricultural production by 2050.

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

A bouquet for De Lier

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Steve Goff’s off to Arizona

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Seven jumbo jet loads of children crash into mosquitoes every day

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Herbicide resistance: an opportunity for Syngenta!

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Syngenta Fellows Annual Conference 2008

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

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

Carolyn Riches goes Out and About

Mike Bushell

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

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

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The Biokinetics Group is a global

Dave: “It is in the development and

resource and works on all herbicides,

marketing areas where I think we have

fungicides, and insecticides used on the

had most impact over the years and

In addition, his

where there have been some unique

group has worked on such diverse areas

opportunities to become involved with

as

plants,

global product launches and ‘key

mosquito nets, shower curtains, and

influencer’ events, telling the biokinetics

even concrete blocks. The group works

stories behind how Syngenta’s products

across all phases of the business from

deliver their effects.”

world's major crops. turf

grass,

horticultural

early-stage chemical synthesis, through As Dave says, it’s all been about

optimisation and development stages, and finally to established products in the

“influencing the influencers” and one of

marketplace. A key part of his work is

Syngenta’s biggest successes has been

studying

how

Syngenta

in the story of the azoxystrobin based

materials

products, especially Amistar®, Quadris®

compare with competitor molecules.

and

Dave: “The biggest development over the last twenty years has been the increase in analytical sophistication both in terms of the ability to quantify molecules and to identify their metabolites.”

Visualisation has come on a long way

Heritage®.

Along

with

plant

pathology, resistance biology, chemistry, But it’s not always that easy, as Dave

regulatory and environmental stories, this

says: “We also need to explain why we

was the first time that a concerted

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

science platform had been taken out to

The Biokinetics group operates in

the wider world and been presented by

controlled environment facilities such as

the scientists themselves.

glasshouses,

and,

with

increasing

frequency in the field, working with

So what would Dave like to see in the future?

product formulations using commercial

Dave: “The biggest advance would be an

sprayers – and on farms as well, which

ability to visualise chemical localisation at

are the macro end of the process. At the

a cellular and sub-cellular level. Ideally we

micro end, the group’s research involves

would do this without using radio-labelled

too, especially in terms of image

being able to observe what is happening

molecules, and to do this with the same

resolution and manipulation; Syngenta

on the leaf, insect or fungal surface itself.

‘point-and-shoot’ ease and sensitivity

was the first to use phosphor imaging

Microscopy is a fundamental part of

that we can with radioactively labelled

routinely as a method to visualise

understanding the whole biokinetic

materials in whole tissues. There are

radioactive molecules in plants as part of

picture and the group use electron, light

techniques out there, but nothing that

the ‘selling story’ and this has been a

and confocal microscopy techniques to

works in the timeframe we need to work

visualise events on and in the target.

in – yet.”

consistent feature in technical launches for many of Syngenta’s products.

In 1979 Dave Bartlett graduated from the Dave: “In the last five years we have

University of Bath, UK, with a degree in

Dave: “We study all the parameters that

become increasingly involved in research

applied biology and went to work for the

can influence how a pesticide behaves in

for the seeds, flowers and vegetable

Soil Science group at ICI. In 1985 he

the time-frame of its biological effect, this

businesses. We’ve even looked at the

moved to the US to work with ICI

can mean from minutes to months.

way harvesting can be made easier, for

Americas carrying out regulatory studies

example making courgettes (zucchini)

on the compounds which were eventually

There are many factors which influence

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

marketed as Force®, Karate® and Cultar®.

the way a pesticide works such as spray

pests which they look at. They also carry

Then in 1990 he came to Jealott’s Hill,

retention, redistribution on the target after

out visualisation of wood, tree trunks,

joined Exploratory Plant Sciences (Plant

spray, rain fastness, vapour movement,

termite barriers, hairs and even the leg

Physiology section), and set up what

uptake, translocation in and on the plant,

joint of a weevil. Dave says that ant

became the Biokinetics Group.

and the rate of degradation of the

colonies have also featured in their work.

molecule. All are quantified to establish a

sm

picture of why we see the effects that we do.”

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Time to introduce some new blood into the elite stock of maize (corn)

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

There’s exotic maize and elite maize. The former varieties are the uncultured ruffians strong and sturdy but of doubtful ancestry, the latter are the aristocratic wealth-producing varieties that 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 220 billion litres (60 billion US gallons) of bioethanol to be produced annually by 2030. Already there 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 now providing it – and not only in the Midwest where most of it is made. Production has been helped by allowing bioethanol plants to be governed by the same laws as distilleries and not 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 make US maize more efficient and to require less water. That’s what John Arbuckle is working to achieve and there are plenty of wild varieties of maize, technically referred to as ‘land races’ from which to choose. Cultivated maize is having some of its alleles replaced by those from older native strains. This approach is complementary to conventional genetic

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Science Matters Keeping abreast of Syngenta R&D Summer 2008

modification in that it is not introducing alleles from different species into the gene pool, but merely transferring from maize to maize beneficial traits that have been missed down the centuries of selective breeding.

The initial list of 300 potential allelic donors was narrowed down to 134 based on the genotypic data using SSRs (simple sequence repeats) and gene sequences. From these, 65 diverse inbreds and 69 individual representatives of land races were selected for platform development, based on molecular distances as well as on the authoritative

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called the shaggy-like kinase, - we see 8 alleles (variants) of this kinase in our elite germplasm. However when we survey landraces and non-elite material we find at least 10 additional variants of this specific kinase.

By breeding, we are re-introducing some kinases from landraces and non-elite material and some are indeed better than those in existing elite lines.

The domestication of maize started in Mexico and then spread both north and south with native people selecting different aspects to improve the crop for their own needs. In the US there was particularly strong selection and a lot of the genetic diversity of the wild species was lost. Maize has 10 chromosomes and there are centimorgan mapping units across all these chromosomes giving a total of 2,500 centimorgans. It is now possible to transfer a single centimorgan from an exotic to an elite strain and test what effect it has.

Climate change is being felt in the USA where farmers are now having their water for irrigation rationed. They can offset this to some extent by being more efficient in the way that they use it. Maize can cope with drought but not at the critical time of year when the plant is in the juvenile and reproductive phase. No rain in the second half of July and a farmer stands to lose more than half his crop, three quarters in really bad times. A more

permanent solution would be to grow a variety of maize that is more drought tolerant. However, improving drought tolerance must not compromise other beneficial traits. Resistance to local diseases and standability are also being investigated. Without good standability a crop may be impossible to harvest because much of it is laying flat on the ground.

This year Syngenta is testing a commercial line that contains targeted alleles from exotic germplasm that confers yield stability under drought stress. “Such maize is the high profile target that we are aiming at” explains John. Approaching old questions with new ideas is how John sees things, in this case bringing together allelic diversity, molecular markers, and genomics. “I want to get people thinking beyond traditional breeding methods and to think in terms of these concepts.”

There is every indication that he and his colleagues 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

classification of races of corn published in 1988 by Major Goodman and William Brown.

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

The key thing in the area of molecular marker development and precision breeding is to take small segments of DNA from land races and put them into the elite breeding pool, without bringing other traits with it” is how John explains it.

“Advances of the past 15 years have made this possible.” Kinase, the phosphate transfer enzyme, is a case in point. In the current pool of cultivated maize there is much less than in the land races. For one specific kinase typre

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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Toxicology team ensure that ants don't win

Thiamethoxam is a broad spectrum insecticide ideal for use against crop pests, turf pests, 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 research by a dedicated Toxicology Team – as Richard Peffer (Senior Toxicologist, Greensboro) explains.

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

it has resulted in a much wider ability to

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

register and sell products containing

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

thiamethoxam in the US, Canada and in

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

other regions.

Waechter, Edgar Weber, James Noakes, Mervyn Robinson, Sara Lloyd, Richard Peffer and Patrick Rose. Together the group opened new doors for thiamethoxam. The

Thiamethoxam can cause liver cancer in

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

mice because of two metabolites. The

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

first of these, in which the methyl group

would allow them to move away from conservative default assumptions.

on nitrogen has been lost (CGA330050), affects cholesterol biosynthesis and

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

causes mild liver dysfunction, which

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

appears within 10 weeks. Decreased

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

cholesterol level in plasma was one of the

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earliest effects of thiamethoxam in mice,

USA in the Human Safety Group at

and it did not occur in rats. A second

Greensboro. This group’s novel results

metabolite (CGA265307), in which ring

with thiamethoxam, and their use of the

opening has occurred, inhibits the

ILSI Framework to critically evaluate the

enzyme iNOS (inducible nitric oxide

mode-of-action and its relevance to

synthetase).

humans, can be read in three landmark papers in the journal Toxicological structural

Sciences published in 2005. As a final

similarity of the major mouse metabolite

icing on the cake, the team won the

CGA265307 to known inhibitors of iNOS,

prestigious "Best Paper" award from the

and this insight led the team to do

Society of Toxicology for this series of

Trevor

specific

Green

in

noted

vitro

the

experiments

that

papers, chosen from a list of 300

demonstrated its potency for inhibiting

nominated papers!

this regulatory enzyme. When iNOS is inhibited, it no longer signals a cell to turn

If you’d like to know more about the

off the normal process that removes

Team member Tim Pastoor, Principal

group’s research consult the following

damaged cells (apoptosis), and so mild

Science Advisor in Greensboro, had

papers:

liver dysfunction spreads to become

earlier participated in an ILSI (International

more pronounced liver damage. In

Life Sciences Institute) work group drawn

Trevor Green, Alison Toghill, Robert Lee,

response to the hepatotoxicity, which can

from

and

Felix Waechter, Edgar Weber, and James

be seen as increased necrosis of cells by

government, which provided a road-map

Noakes, ‘Thiamethoxam induced mouse

20 weeks, cell proliferation accelerates as

or “framework” on how to evaluate

liver tumors and their relevance to

the liver tries to replace damaged cells

animal mode-of-action data and its

humans. Part 1: Mode of action studies in

and maintain normal function. The rapid

relevance to humans. In 2003 the group

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

rate of cell division enhances the chance

published its framework document (Meek

industry,

academia,

of a spontaneous mutation occurring and

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

Trevor Green, Alison Toghill, Robert Lee,

of these transformed cells surviving in

EPA,

industry

Felix Waechter, Edgar Weber, Richard

liver tissue. This results in an increase in

researchers. This framework document

Peffer, James Noakes, and Mervyn

mouse liver tumors after more than one

provided the lens through which some

Robinson.

highly detailed biochemistry could be

mouse liver tumors and their relevance to

viewed and evaluated.

humans. Part 2: Species differences in

year of high-dose treatment.

academic,

and

A second critical revelation from the team’s

research

differences

in

is

that

species

metabolism

‘Thiamethoxam

induced

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

The

mode-of-action

data

for

produce

thiamethoxam produced by Trevor Green

Timothy Pastoor, Patrick Rose, Sara

differences in effects. In rats and humans

and the research team fit into this new

Lloyd, Richard Peffer, and Trevor Green,

the same metabolites form as in mice,

framework just like a hand into a glove.

‘Case

but in such small quantities that liver

Syngenta has always set the bar high in

evaluation of the human health relevance

dysfunction and other changes that lead

terms of the level of science needed to

of thiamethoxam-related mouse liver

to cancer do not occur. A different

understand what’s happening with our

tumors’, Tox. Sci. 86, 56-60 (2005)

metabolic pathway is more dominant in

products. This has allowed us to provide

rats and humans, as illustrated in the

the EPA with the scientific certainty to

figures

even

move away from restrictive assumptions

Dellarco,

CGA265307

about our products, while establishing us

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

treatment of mice for up to 20 weeks by

as a leader in the areas of investigative

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

itself did not produce the liver damage

toxicology and mode-of-action research.

Framework

below.

demonstrated

The that

team

that occurs in mice with thiamethoxam; it took the 1-2 punch of both CGA330050

Study:

Weight

of

evidence

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

Hill,

for

R.N.,

Human

Lehman-

Relevance

Analysis of Information on Carcinogenic The thiamethoxam mode-of-action work

Modes of Action’, Critical Revs in

and CGA265307 to generate the mouse

was carried out in the in the UK at the

Toxicology, 33, 591-653 (2003).

liver effects.

Central Toxicology Laboratory at Alderley Park, in Switzerland at the Biochemical

sm

Toxicology section in Basel and in the

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Product Biology:

the sun never sets on Syngenta field trials

Klaus Gehmann is a man with a mission: to make every field trial count. Achieving it would ensure Syngenta seeing the successful launch of more new products in the years ahead. Klaus also seeks to achieve an equally challenging objective: for Syngenta to outperform 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

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Science Matters Keeping abreast of Syngenta R&D Summer 2008

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

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Klaus: “We are proud to have a superb field force in our key countries. They know how to make it happen and have the ‘can-do’ attitude which makes all the difference.

Experienced colleagues train newcomers from new growth markets such as India, China and Russia.”

competitive advantage because speed really can matter. Finally comes the allimportant 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”

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.

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.

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

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

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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.

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.

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

Part of the company is a purpose-built distribution facility at Maasland, a few

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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.

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.”

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.”

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.

sm 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

Science Matters Keeping abreast of Syngenta R&D Summer 2008

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Steve Goff’s off to Arizona

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

Steve did his PhD in molecular genetics

computational

cyber-

Biology, paid tribute to his work: “While I

at Harvard in 1985, then worked with

infrastructure to solve the major research

am sad that we are losing Steve and his

Biogen S.A. Geneva, before moving to

problems in plant biology – the so-called

ability to consolidate data, ideas, and

Tuft’s Medical School. He switched his

Grand Challenges.

thoughts, we will continue to strengthen

research

focus

in

1987

to

tools

and

our relationship with public sector

gene

expression in plants at the Plant Gene

“Steve’s new position will give us insights

scientists through him. Syngenta will

Expression Center at the USDA and

into how Syngenta can collaborate and

continue to offer support which facilitates

University of California Berkeley.

benefit from the exciting advances being

the interaction and collaboration between

made at the University of Arizona and the

our company and academics.”

Steve was awarded “Research Leader of the Year” by Scientific American in 2002 for his work on sequencing the genome of rice, which was the first crop plant to be sequenced.

He was also very interested in human flavour perception and he has written 50 original research papers and filed even

broader NSF initiative with which it is associated.” says Martin Clough, Head of

Steve was clearly moved: “I'd like to

Biotechnology R&D.

thank you all for the exciting years at Ciba, Novartis, TMRI, and finally back at

Steve gave a farewell lecture on 29 April 2008 at the SBI Science Forum.

His talk was entitled ‘Recent Learnings from Genomics: What we’ve learned about genes and what opportunities these learnings create.’

more patents. In 2003 when Syngenta’s

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 addressing

for

plant the

genomics

Grand

and

Challenge

questions in Plant Sciences. Some of these

should

be

very

useful

for

Torrey Mesa Research Institute (TMRI) in

During it he reviewed recent literature

companies like Syngenta, and I hope to

San Diego closed, Steve moved to

findings and discussed why it is so

be able to come back and describe

Syngenta Biotechnology Inc (SBI), North

difficult to associate genes and the traits

progress on this NSF-funded effort in the

Carolina, to become a Senior Syngenta

they cause. He went on to describe

future.”

Fellow. His group’s efforts were focussed

some recent developments in genomics

on the science at the intersection of plant

and plant science that will impact

and animal biology. In the August 2004

Syngenta's delivery of both Transgenics

can reach him at his personal e-mail

issue of Scientific American, he co-

and Native Traits products, and will be of

address stephenagoff@yahoo.com or at

authored the cover article with John

interest to the scientists trying to

Arizona sgoff@email.arizona.edu and it

Salmeron entitled “Back to the Future for

understand

you’d like to read his last seminar you can

Cereals.”

Syngenta's chemical products.

download it from the Syngenta database.

Now Steve has a faculty position at the

After his lecture, Steve was joined by his

sm

University of Arizona as the Director of

co-workers in a celebration of his

Community Interactions for the NSF-

contributions to Syngenta and his 16 year

funded iPlant Collaborative. The $50

tenure with the company. Erik Legg,

million project is designed to develop

Group Leader for Integrated Genome

the

mode-of-action

of

Readers who would like to contact Steve

Science Matters Keeping abreast of Syngenta R&D Summer 2008

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Seven jumbo jet loads of children crash into

mosquitoes every day

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

It’s the job of those in the Formulation Development Section to take the raw active ingredients such as fungicides, herbicides or insecticides which are made by the synthetic chemists and turn them into the products that people can use. And it’s not only bulk purchasers 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 and the World Health Organisation (WHO) estimates that 300 million people a year suffer from it.

16

Science Matters Keeping abreast of Syngenta R&D Summer 2008

Every day the number of children actually dying from malaria would fill seven jumbo jets, such is the terrible toll this disease takes.

Lesley Silverthorne’s project was to design an insecticide which could be applied to mosquito bed nets to provide long-lasting protection against these insects. Previous products of this type tended to be washed off when the bed net was laundered and people would

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controlled manner. Lesley: “This was a particularly tricky challenge. If you bound the active ingredient too tightly to the net you could lose the knock-down effect.”

then forget to reapply more. The challenge that Lesley’s team faced was to devise a formulation which was washfast, which retained its activity for long periods, and which was easy to apply by those who purchased the insecticidal kit, or who were given it by their government or aid agency along with a bed net.

Lesley: “We provide Icon®Maxx users with an outer bag into which they can measure the correct volume of water and into which they then dilute the Icon®Maxx before immersing their bed net and soaking it for at least 30 minutes. It can then simply be left to air dry and this is sufficient to allow the binder to stick the capsules to the netting.”

So how long does an application have to last? Lesley: “A typical net would last the householder for up to three years. During this time they can wash the net if it becomes dirty but the capsules will remain attached even if the nets are washed with the aid of a detergent.” The WHO has approved Icon®Maxx after bed nets treated with it successfully passed their test of still being active after 20 washes. Competitor products failed to survive this stringent test.

The challenge was to find a way of bonding the insecticide to the net but ensuring release of the insecticide in a

The attachment of these minute capsules to the net fibres is a more physical bonding process. The binder is basically an ethyl vinyl acetate film-forming copolymer. The key is to use the right polymer at a specific rate to ensure that treated nets can be simply air dried without the need for curing with the resulting treatment being wash fast and the capsule contents are still bio available.

The active agent in Icon®Maxx is λ(lambda)cyhalothrin (a fluorinated pyrethrin) which is a very effective insecticide and so application rates can be kept low.

The answer was to encapsulate the insecticide in a polyurea shell and then stick the minute capsule to the bed net fibres with a binder.

In the research phase Syngenta scientists in the UK and Switzerland looked at more than 60 binders and various bed net fibres including nylon and cotton. The formulation chemistry was done at Jealott’s Hill, UK, by David Barnett and Beverley Mason, and the biological testing was done at Stein, Switzerland,

by Andy Bywater. The aim was to balance insecticide release with long term activity and an ability to survive laundering – and they did it.

The capsules are formed by incorporating isocyanate precursors, polyphenyl isocyanate and toluene diisocyante, into an emulsion system containing the insecticide within the oil phase. The isocyanates react first with water at the emulsion droplet surface forming amino groups which then go on the react with other isocyanate groups to generate polyurea linkages, effectively creating a shell around the capsule with the insecticide inside.

Cyhalothrin is active at a very low level and there need only be 50 mg per square metre of the net to be effective against mosquitoes. Tests were also carried out to show that even if a child chewed its mosquito net then its health would not be at risk.

Now, after her maternity leave, Lesley has returned to the Formulation Development Section at Jealott’s Hill to work on new products. Needless to say she has fitted her baby Amelia’s pram with a mosquito net.

Lesley Silverthorne has a degree in chemistry and is a graduate of the Royal Society of Chemistry. She joined ICI at Jealott’s Hill in 1987, relocated to Kent for 10 years and then returned to Jealott’s Hill in 2002 as a member of the Formulation Development Section, which is headed by David Sadler. It’s there that she and her team have waged war against diseases like malaria by forging a new weapon to defeat mosquitoes: Icon®Maxx. This was launched at the end of 2007 and sales are already exceeding expectations.

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a real threat for agriculture but an opportunity for Syngenta!

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

18

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Herbicide resistance weeds are a serious

Resistance is a fact of life. It occurs

threat to agriculture and food production.

worldwide where herbicides have been

Syngenta was quick to recognize this and

used extensively. For example in Australia

has invested significantly in better

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

understanding and managing resistance.

grass. These and other weeds have

Scientists from the resistance research

evolved to become resistant. Lack of

DNA based methods are then developed for the early and unambiguous detection of resistance, thus limiting its spread in the field.

team at Jealott's Hill have developed an

diversity in farming methods and overuse

array of scientific methods for uncovering

of previously highly effective herbicides

the mechanisms by which weeds eveolve

have allowed plants with a slightly

resistance.

These have lead to the

different segment of their genome to

Thanks to their deep understanding of

development of new techniques to detect

survive. Thereafter their progeny will

herbicide resistance mechanisms they

resistance in the field.

cross and further spread across and to

have generated some unique weed lines

adjoining fields.

for screening new herbicides in research

Using their

scientific results they have empowered

that would overcome resistance.

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

So what happens when a farmer discovers a weed that has survived a herbicide treatment in his field?

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

in 2002 as their technical specialist in

collaborators worldwide.

charge of herbicide-resistance. His colleague, molecular biologist Richard

Deepak: “I see myself as the link between

Dale, did his degree in genetics at Leeds

the scientists at Syngenta and the

University, UK, before joining Syngenta’s

growers. We make sure that each and

Bioscience Department.

every one of our experiments is designed for the mutual benefits of Syngenta and

They are members of a remarkable team

its customers. Once we have confirmed

with skills across diverse areas of

resistance in a weed and understand its

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

mechanism we are in a better position The first step is for seeds from the suspect plants to be collected and sent

we

for

capabilities

resistance

confirmation

under

controlled glasshouse conditions at

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

can

demonstrate in

a

Syngenta’s competitively

advantageous way.”

Jealott’s Hill. This has to be done because the weeds might just have

As

survived due to sub-optimal spraying

Manager, indicates: “Scientific support

conditions in the field. However, if the

was of significant help in the launch of

plants remain healthy the next step is to

Axial® on the UK market, demonstrating

Iain

Hamilton,

Field

Technical

develop a solution based on mixtures

to potential clients that this was a

and sequences of existing herbicides.

herbicide that was different from those of

Simultaneously Richard will take a

give advice and support to growers and

population). Deepak views herbicide resistance as a real opportunity rather

once again to protect crops. In so doing

our competitors. We have the ability to sample of leaf and extract the DNA. He

advisers about how to tackle difficult

then compares its gene sequence with

grass weeds in the field and that’s a real

the DNA of a known herbicide-sensitive

bonus for us.”

plant and finds where it differs. Very often the difference should point to the cause

sm

of resistance.

and overcoming resistance.”

Science Matters Keeping abreast of Syngenta R&D Summer 2008

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Syngenta Fellows Annual Conference 2008

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

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The Fellows’ Annual Conference was

challenge to utilise the potential of the

networks, and to hear presentations from

held in April in Zurich, Switzerland and

ACE program to deliver solutions to our

professors

included a colloquium devoted to Applied

customers.”

Mulqueen, Senior Syngenta Fellow and 2007

Crop Enhancement (ACE) which was

Core

and

researchers.

Team

Chairman,

Pat was

held at the Syngenta site at Stein. The

After lunch there was a brief question and

particularly impressed: “The visit to ETH

focus was on improving networks, both

answer session, and later the attendees

allowed us to meet key researchers. For

internally and externally, the better to

divided into small groups focusing on

me, the particularly exciting talks were by

drive technology and scientific progress

idea generation in five key areas for ACE

Professor

within the company.

“With technical leadership, know-how and expertise, the Fellows aim to influence the future of their functions and overall business”, explained David Jackson, Fellows Core Team Member.

Starke

on

nanoparticle

improvement. These areas included:

technology (using inorganics such as

vigour;

soil

calcium phosphate as a model) and

nutrients; abiotic stress; and quality

Professor Seeburger and his students

enhancement. Each group narrowed

about precisely constructed polymeric

their suggestions and ideas for the next

sugars

steps down to five; and shared their

substrates.”

maturity

management;

in

defining

adhesion

to

findings with the group in a plenary session. The ACE group, with Fellows

The Fellows spent the final day learning

involvement, will now deep dive into the

how to better understand the importance

findings and identify projects of most

of networking. External consultant, Ray

interest to Syngenta.

Smith, laid out the foundations of effective networking: mutual trust, mutual the

objectives and mutual interests. In small

presentation of awards to the 2007

group sessions the Fellows focused on

The ACE colloquium saw a full program

Science and Technology Prize winners.

their main areas of improvement for this

of speakers, themed workshops, and the

David Lawrence praised the three

year which they identified as networking,

awarding of science prizes, all of which

recipients: Gabriel Scalliet and Olivier

behaviour, brand and innovation.

combined to create an atmosphere of

Loiseleur of Stein, and Judith Bowler of

The

Colloquium

also

saw

sharing, brainstorming, and celebration

Jealott’s Hill. Each winner delivered a

for the 80 participants.

summary of their work.

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

“The Fellows community has been given challenges to deliver more through networking across technical and business silos” says Mike Bushell, head of External Partnerships at Jealott’s Hill.

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

“A pilot training and development

Gabriel: “It is very rewarding to get this prize because it shows that science makes a difference to the company. Innovation makes a difference.”

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

presented by both our internal and external speakers,” said David Lawrence,

The next day, the Fellows spent time at

Head

ETH, Switzerland’s top university, to

of

Global

Research

and

Development. “Syngenta now has the

strengthen

their

co-operation

and

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Out and About Our intrepid reporters, Carolyn Riches and Ashley Collins have been tracking down some more interesting things which Syngenta people have been involved in.

With thanks to Sirku Ploetner.

Go with the flow-reactor “Upgrading the H-Cube to link with a redundant liquid handler is a major leap forward!” exclaims Gavin Bluck, Jealott’s Hill Research Chemist. The H-Cube is a key piece of technology for performing hydrogenation reactions. Using a flowreactor, it generates its own H2 in situ by electrolysis of water. “We’ve discovered and optimised conditions for reactions that weren’t successful by 'conventional' methodology.”

The unit is able to perform multiple smallscale (i.e. less than 0.5 mmol) reactions unattended which he says is great for rapidly investigating optimal conditions and it frees up time for other tasks - or even coffee!

Flexibility has been maintained to cope with large-scale field-trial syntheses. On the day that Gavin first plumbed the H-

22

Cube into the liquid handler, he had a request to hydrogenate several litres of a key intermediate. “Within a couple of minutes, I‘d transformed the unit into being able to cope with large-scale process work…and then I was off!” says Gavin.

Global‘webinars’captureReach-outenergy How can you disseminate information on important Syngenta projects to interested global parties, and at the same time capture their ideas? A ‘Reach-out’ event is the answer. Franz Doppmann and his Development team have harnessed internet seminar (or ‘webinar’) technology to enable live internet broadcasting. Any number of people can join the ‘giant netmeeting’ via their PC and phone. At the end of the broadcast a Q&A takes place, with global participants posing questions via e-mail or over the phone. A follow-up Reach-out event captures thoughts, ideas and energy while still fresh in the mind. Attendees may also spend a couple of days working on issues that arose.

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 week secondment to Jealott’s Hill/Stein as part of a training programme for chemists.

Mangala immersed herself in a research project, having hands-on experience in the labs and greenhouses – something no amount of teleconferences and emails could offer. “I’ve enjoyed the chemistry discussions and meeting a large number of scientists across all disciplines,” says Mangala.

Jealott’s Hill Weed Control Group Leader, Mark Spinney, is clearly impressed: “From my desk, I’ve connected with both Senior Management and the span of our global organisation, as well as gaining critical information about some of our most exciting new products, such as Invinsa®.”

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

Science Matters Keeping abreast of Syngenta R&D Summer 2008

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

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Mathews, Group Leader (JH). “This will enhance her team’s ability to work more effectively, encouraging still greater input into this and future projects.”

Secondments for Goa employees have primarily been for those needing close involvement with projects - further secondments to Stein are planned for two more Goa Chemistry Team Leaders.

Also this year, a Jealott’s Hill / Stein exchange took place between Olivier Provoost and Mario Juerg. Chemists’ self-nominated and candidates were selected by their managers. Rob Lind, Team Leader, Bioscience (Jealott’s Hill) has also completed a secondment in Stein. If you’d like to take part in an employee exchange, your line manager can provide guidance.

In a flash…

Ultra Thin Client (UTC) technology is going on a two month trial at Jealott’s Hill from June. A UTC is like having your PC in your pocket and the ability to log-on wherever you happen to be on site. The scientists trialling the technology will be able to immediately log-on to a central server by inserting an access card into a box next to a monitor. The screen is recalled exactly as when they were last logged-on - instant working, in a flash!

The Discovery Biology Group and two project teams will be trialling the UTCs. With monitors taking up less desk space, office layouts have been designed for interaction and space efficiency. This fits with the project room way of working already in place at Jealott’s Hill: key project members temporarily locate in one room, ‘hot desks’ are available for peripheral members and informal coffee sessions enhance the flow of new ideas.

Jim Mills, Jealott’s Hill Biology Technician: “Having a base in several buildings, I’m looking forward to being able to log-on straight away”. For more information, contact Derek Scuffell, UTC Project Lead.

It’s good to talk…

"The Stein Interaction Centre has already influenced our ways of working by creating numerous spontaneous opportunities for networking and knowledge sharing,” says Mafalda Nina, Research Computational Chemist (Stein) speaking of the new facilities at our Swiss

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research site. Syngenta officially opened the Interaction Centre on April 10th, thereby reinforcing Stein's position as one of five main Syngenta research sites worldwide, specializing in fungicides and insecticides.

High-quality materials, lots of natural light and the well-planned integration of openair and indoor areas all contribute to an atmosphere ideally suited to innovation.

It has also enabled chance interactions where colleagues from Biology, Chemistry and Patents often discuss project details outside of formal meetings. “These opportune moments have enabled me to quickly answer questions with my Biology colleagues, saving time in making phone calls and emailing,” continues Mafalda.

The Interaction Centre with its auditorium, meeting rooms and offices also provides a fine location for scientific exchange and celebrations (internal and external).

Upcoming events planned for the Centre include visits from UK distributors, Swiss agronomy advisors and Syngenta Sales and Marketing.

Hoorah for Project Fuwa Progress of the Syngenta Biotech China Site (SBC), known as ‘Project Fuwa’, is in full swing. With the Land Purchase Agreement signed on April 10th, SBC is looking forward to what the future 21,500 m2 building will add to Syngenta’s Research and Development program.

Currently, SBC is run in a leased facility. In September of this year, temporary laboratory spaces will be set up and ready to use. Additionally, recent campus recruiting events have proven to be very successful. For the fifteen open positions, over 800 resumes were received.

“Syngenta is creating a very positive image of itself. We’ve been able to deliver

the message that we’re committed in China. People like Syngenta, and want to work for Syngenta”, says Liang Shi, Group Leader for the Transformation and Analysis Group. “It’s our hope that SBC and SBI will become closely connected.

We hope to foster an open culture and good collaboration between the sites.”

Mini-Chromosomes Could Yield Mega Results Through the partnership of Syngenta and Chromatin Inc., we are now able to test Chromatin’s gene stacking technology of “mini-chromosomes”. Mini-Chromosomes are developed using select elements from a crop’s existing chromosomes, including the centromere, which provides genetic stability and can help to ensure inheritance of the mini-chromosome. This technology can offer Syngenta a new way to develop stacked traits and speed the time from development to commercialisation. While this new technology is very exciting for Syngenta, it will not replace our current methods: molecular stacking or traditional breeding. “We will evaluate this technology in combination with our own innovative research programs. MiniChromosomes will give us the ability to enhance our product speed to the market and potentially increase the number of traits that can be stacked into one variety” says Roger Kemble, Head of Crop Genetics Research.

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Writer John Emsley is author of several popular science books which deal with everyday chemicals including The Consumer’s Good Chemical Guide, which won 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 Science Matters is published by Syngenta, Jealott’s Hill International Research Centre, 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 packaging waste, 10 percent best white waste, 60 percent de-inked waste fiber and only 20 percent virgin totally chlorine free fiber sourced from sustainable forests.

Cautionary statement regarding forward-looking statements This document contains forward-looking statements, which can be identified by terminology such as “expect”, “would”, “will”, “potential”, “plans”, “prospects”, “estimated”, “aiming”, “on track”, and similar expressions.

Such statements may be subject to risks and uncertainties that could cause actual results to differ materially from these statements. We refer you to Syngenta’s publicly available filings with the US Securities and Exchange Commission for information about these and other risks and uncertainties. Syngenta assumes no obligation to update forward looking statements to reflect actual results, changed assumptions or other factors. This document does not constitute, or form part of, any offer or invitation to sell or issue, or any solicitation 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

Science Matters Keeping abreast of Syngenta R&D Summer 2008