The Bayer Scientific Magazine
EDITION 26 | July 2014
Networking for better healthcare
Cutting-edge global research for medical progress
Strong pods Light plane Special feature: ion channels
New canola variety
increases yields
Test lab for hightech materials
Fundamental research for new treatments
and healthier plants
EDITORIAL
Innovation needs acceptance
and appreciation
Point of view
2
News
4
Interview with Management Board
member Dr. Kemal Malik
24
Masthead
49
MEDICINE
Cover story:
Networking for better healthcare
Collaborating on innovative treatments 14
Transferring knowledge
More transparency in trial data
31
A pioneer in the service of patients
Portrait:
Professor Johannes-Peter Stasch
44
TECHNOLOGY
Dr. Marijn Dekkers, Chairman of the Board of Management of Bayer AG
Otto Bayer Award:
camouflaged ions
Professor Frédéric Merkt
Dear reader,
Technical progress makes a huge impact on the quality of our lives. Just think
about the opportunities that modern medicine now offers us – possibilities that
we would never have dared to dream of 50 years ago. And consider the variety
and quality of the fresh food that is reliably available for us every day. As global
life expectancy figures confirm, we have never had it so good as we do today.
The numbers may vary from country to country, but the trend is positive almost
everywhere.
Oxygen depolarized cathode
Energy-efficient chlorine production
48
MATERIALS
Solar Impulse
Aviation: flying laboratory
10
Hospital hygiene
Germs don’t stand a chance
What seems at first glance to be so ordinary is not something we should take
for granted. Innovation requires knowledge and is therefore dependent on education. Innovation requires space to unfold and is therefore dependent on the
underlying political conditions. And innovation requires the backing of society.
Because without appreciation and comprehension of what these life-enhancing
innovations mean, there will be no more progress. We won’t be able to treat new
diseases that appear, and the diseases that are incurable today will remain incurable. The same applies to agriculture. We will need to substantially increase the
productivity of the available arable land if we want to be able to feed nine billion
people in 2050. Major challenges await us.
AGRICULTURE
Based on “Science For A Better Life,” we aim to further improve the lives of
millions of people. This is what motivates us each day at Bayer. I hope that you
will continue to accompany us on this journey.
Molecular gatekeepers
Best regards,
32
38
Rice
All-round talent for rice fields
6
Canola
Strong seed pods
26
SPECIAL FEATURE
Ion channels
40
FOUNDATIONS
Bayer foundations promote science,
medicine and social innovation
34
CONTENTS
Cover story
Aviation as a catalyst
10
Networking for better healthcare
Materials experts develop many of their ideas
­initially for the aviation industry. Bayer scientists
are testing some of their new premium materials
in the solar plane Solar Impulse.
Helpers in the rice field
Bayer scientists like structural biologist Dr. Martina Schäfer (photo above)
are constantly searching for new technologies and creative approaches
to help them develop effective treatments. To offer patients with cancer,
cardiovascular disorders or lung diseases completely new therapeutic
options, Bayer‘s researchers from all disciplines are collaborating with
top international scientists in the United States and China. 14
6
Bayer scientists have developed a new herbicide
for rice farming in Asia. It not only saves time and
labor but also secures precious harvests.
Photos: Peter Ginter/Bayer AG (3), Bernhard Moll/Bayer AG (1), Amac Garbe/ein-satz-zentrale.de (1), Jean Revillard/Rezo/Solar Impulse (1), Manfred Kage/Okapia (1), Ingo Rappers/WiWo (1)
Bayer
Bayer-Stiftungen34
Foundations 34
Special feature
Ion channels
The Bayer Science & Education Foundation promotes
cutting-edge research and junior talents. The Bayer
Cares Foundation supports social innovations like the
medical student initiative “What have I got?” (photo).
New variety of canola
26
Bayer scientists have developed a variety of canola
with particularly robust seed pods. This ensures that
the bulk of the harvest can be used instead of ending
up on the ground.
Nerve cells – like the neuron shown above under 3,000-fold magni­­fication – communicate with each other. Ion channels play a vital role
in this process and are therefore interesting targets for medical and
crop protection research. Bayer scientists are leveraging synergies
in fundamental research.
40
Bayer research 26 July 2014
1
2
Bayer research 26 July 2014
POINT OF VIEW
RESEARCH, PLANT,
HARVEST
Rainforest
Savanna
Subtropics
29
million
hectares of
land in Brazil
are covered by
soy fields.
Photos: Ole Leifels/Kubikfoto (1), Dirk Hansen/Bayer AG (1)
Brazil is a country of many challenges. Its different
­climate zones pose plenty of problems for farmers: while
in southern Brazil, plants have to ripen quickly to avoid harvest
­losses due to frost, very different problems apply in the hot, dry
interior of the country, and the tropical regions in the midwest
are particularly strongly affected by insect pests and diseases.
Bayer CropScience researchers are therefore developing new,
specially adapted varieties and crop protection agents and thus
contributing to the success of champion soybean producer Brazil.
Using the research app, you can accompany one of Bayer’s
­scientists to a soy field in Brazil: www.research.app.bayer.de/
en/26/point-of-view/
Loreta Marra and Danilo Oliveira (photo left, left to right) from Bayer CropScience
inspect soybean plants under the Brazilian sun. In Lyon in France, Bernard ­Pelissier
and Emanuelle Serillon-Bert (photo above, left to right) are working on producing
herbicide-resistant soybean plants and ways of protecting them against voracious
insect pests.
Bayer research 26 July 2014
3
NEWS
Acute coronary syndrome:
New indication for rivaroxaban
Research is an innovation driver: Bayer scientists like Dr. Susanne Röhrig are constantly
working on developing new active ingredients in the area of anticoagulant treatments.
Research collaboration:
Plastics:
Alliance in crop protection
Putting climate
gas to good use
To identify new active ingredients and
plant traits – this is the objective that Bayer
CropScience and Targenomix GmbH, a spinoff of the Max Planck Institute of Molecular Plant Physiology, have set themselves
in a five-year research collaboration agreement. The scientists want to better understand the metabolic and regulatory processes
of crops so that they can develop new
solutions. “Farmers worldwide urgently need
innovations to further increase both yields
and the quality of harvested produce,” said
Dr. Axel Trautwein, Head of Small Molecules Research at Bayer CropScience. The
partnership should help scientists clarify
as yet unsolved aspects of plant biology.
4
Bayer research 26 July 2014
Good harvests: new findings in plant biology
could help increase yields.
Harmful climate gases are being put to good
use in polyurethane production. In collaboration with partners from industry and academia,
Bayer has developed a process for using carbon dioxide as a component of a chemical precursor for foam. The Group plans to invest EUR
15 million in the construction of a production
line for these precursors, known as polyols, at
the Dormagen site. The objective of the publicly funded Dream Production research project
is to produce CO2-based polyols beginning in
2016. The plant will have an annual production capacity of 5,000 metric tons. The experts
have already thoroughly tested the process in
a pilot plant.
Photos: Peter Ginter/Bayer AG (1), Alabiso/agrar-press (1), Ocean/Corbis (1), Your Photo Today/Phanie (1)
Severe pain suddenly flares up in the chest, sometimes radiating into the arms, neck, lower jaw and
abdomen, usually without any prior physical effort,
and often lasting for 20 minutes and longer. Frequently associated with fear, nausea, sweating and
shortness of breath, acute coronary syndrome (ACS)
is a serious medical condition that requires emergency treatment, as patients are at a high risk of
suffering a fatal event. But even after successful
acute treatment of the heart attack, these patients
have an elevated risk of suffering sudden cardiac
death or another heart attack. Since June 2014, ACS
patients in Germany with elevated cardiac biomarkers who have not previously suffered a stroke or
transient ischemic attack (TIA) have a new option
for secondary prevention after ACS: 2.5 mg rivaroxaban in combination with standard antiplatelet
treatment. Rivaroxaban inhibits blood coagulation and thus affects the second signal pathway
after platelet aggregation that contributes to the
formation of dangerous thrombi in blood vessels.
Rivaroxaban has been approved for more indications than any of the other novel oral anticoagulants to date. The active ingredient is registered in
more than 120 countries across all indications. In
Germany alone, use of rivaroxaban is approved in
five indications.
NEWS
New technology:
Global network:
Partners for new rice varieties
New laboratory
in Dubai
Rice feeds the world, but climate change is increasingly having an impact on the cereal, with
soil salinity and flooding reducing harvests. One solution is hybrid rice varieties, which produce higher yields than conventional rice plants. What’s more, hybrid rice is generally more
resistant to stress. Bayer CropScience has now entered into a multi-year project with the
Israeli company Kaiima Bio-Agritech Ltd. to develop more hybrid varieties. Bayer is bringing
its rice breeding material to the collaboration, while Kaiima is contributing its new EP™ technology, which can be used to significantly increase the yield of this food crop. The technical
term for the procedure is genome duplication, which is a natural process that enables plants
to adapt to environmental stresses. The plant experts also use naturally occurring genetic
variations to endow the hybrids with additional resistance to diseases and pests, and to make
them less susceptible to soil salinity and flooding.
As far as the eye can see: a large portion of the global rice production is grown on the
rice terraces of Asia. Bayer’s scientists are working on varieties that are adapted to suit the
­environmental conditions.
Environmentally friendly construction is all the rage.
Bayer MaterialScience is supporting this trend all
over the world with sustainable solutions and new
high-tech raw materials. For instance in the Middle
East: the company has opened a new laboratory
for coatings, adhesives and specialty chemicals in
Dubai. The lab is located at DuBiotech, the leading cluster for life sciences in the region. “In keeping with our vision and mission, Bayer is bringing
innovative and sustainable solutions to the region,”
said Marwan Abdulaziz Janahi, Executive Director
of DuBiotech. The Bayer coatings experts are now
offering local technical support to customers in
the Middle East and Africa. Among other things,
the new lab is expected to accelerate the development of polyurethane products such as sealants
for concrete joints and airport taxiways and also
solvent-free coatings for piping. Construction, automotive and industrial coatings as well as coatings
for plastics, wood and furniture are the other core
areas on which the materials experts are focused.
The laboratory is outfitted with state-of-the-art
testing and applications equipment, and will collaborate closely with the global Bayer competence network for coatings. “We have to align our resources
with market requirements, which is why we are
making targeted investments in specific regions,”
says Daniel Meyer, Head of the Coatings, Adhesives,
Specialties Business Unit and member of the Executive Committee of Bayer MaterialScience.
Acquisition:
Over-the-counter medicines
Skin creams, headache tablets and throat sprays: many medicinal products
are available without a prescription in different retail channels around
the world. Bayer AG has acquired the Consumer Care business of the U.S.
pharmaceutical company Merck & Co., Inc. and thus taken over its prescription-free medicines division. The acquisition makes Bayer the world’s
second-largest provider in this product category. The acquired business
mainly comprises products for disorders of the upper respiratory tract and
gastrointestinal conditions as well as dermatological, sun care and foot
health products. “This acquisition marks a major milestone on our path
towards global leadership in the non-prescription medicines business,”
explained Bayer CEO Dr. Marijn Dekkers. The purchase price was US$14.2
billion. The transaction also includes a strategic research collaboration with
Merck in the area of soluble guanylate cyclase (sGC) modulation for the
treatment of certain cardiovascular diseases (see also pages 25 and 46).
Advice for patients in the pharmacy: prescription-free medicines and vitamin mineral supplements are an important part of Bayer’s portfolio.
Bayer research 26 July 2014
5
A NEW HERBICIDE FACILITATES RICE FARMING IN ASIA
All-round talent for rice fields
Rice is the number one food in Asia, and growing it demands a lot of manual labor from small farmers. Researchers at
Bayer CropScience have now developed a new herbicide that combats numerous weed species, saving rice farmers time
and labor and securing harvests.
Rice is the elixir of life in Asia. These
small, silvery grains feed a large proportion of the world’s population. Along with
wheat and corn, rice is one of the major
staple foods of the world; some 3.5 billion people eat rice e­ very day. India and
China are among the main producers of
the cereal. But rice plants do not produce
a good harvest all by themselves; they
require the daily toil of countless small
farmers on the rice terraces of Asia. With
hard manual labor and largely traditional methods, these small-holders harvest
about 90 percent of the world’s entire
rice crop, according to the United Nations
Food and Agriculture Organization (FAO).
Rice farming in Asia is highly labor-intensive and often not very profit­
able. Researchers at Bayer CropScience
are therefore working on improved
rice varieties and other ways to increase yields and facilitate cultivation
in order to safeguard rice farmers’ in-
719
million tons
of rice were produced
worldwide in 2012. In 2000,
the figure was 597 tons.
Source: FAOSTAT
6
Bayer research 26 July 2014
Teamwork in the greenhouse: project leader Coralie van Breukelen-Groeneveld
(second right) and Bayer researchers Dr. Chieko Ueno, Dr. Christian Waldraff and
Dr. Chris Rosinger (left to right) check out rice plants, always with an eye to helping
farmers in their rice fields in Asia.
comes. After all, the number of rice farmers in Asia’s rural regions is dwindling as
urbanization continues to draw increasing numbers of people to the cities. A
new rice herbicide named Council™ (active substance: triafamone) may become
an important instrument for relieving
some of the burden on small-holders in
Asia. It is currently showing off its capabilities on test fields full of high, lush,
green rice plants: not a single weed can
be seen growing in between them. “Triafamone exhibits very strong activity
against weeds in a wide range of growth
stages,” says Bayer researcher Shinichi
Shirakura. He is the biologist responsible
for supervising field testing of the new
herbicide and is absolutely delighted with
the results: “­ Triafamone helps combat a
whole range of grasses and sedges, even
those that have developed resistance to
many common crop protection agents.”
The rice plants themselves remain unharmed. The herbicide has a highly targeted effect, which is due to a critical
difference between the metabolism of
rice plants and weeds.
On target with biochemistry:
substance only affects weeds
Although the rice plants absorb the active
substance through their roots and leaves
just like other grasses, they do not activate it. According to current findings of
the Bayer researchers, biochemical processes are at the root of this mechanism:
the weeds themselves activate the substance by dissociating a small but critical
part of the molecule. The activated tri-
Photos: Peter Ginter/Bayer AG (4), Gaby Gerster/Bayer AG (1), IRRI Images (1), private/Bayer AG (1)
Rice AGRICULTURE
Strenuous manual labor: small-holders like Doan Thi Hong and Phan Minh Phat (from left) from Vietnam invest a lot of time and effort in
planting and harvesting rice.
Bayer research 26 July 2014
7
Practice test: innovations from Bayer laboratories are urgently needed in fields in Asia, for instance for the rice harvest in India (photo left). Bayer
researchers such as Shinichi Shirakura and his marketing colleagues (photo right) monitor the effects in the field, for example in Thailand.
afamone blocks the enzyme acetolactate
synthase, putting a halt to the production
of protein that is vital to the survival of
the unwanted plants. “The weed withers, its leaves fade and it dies in one, at
most two weeks,” says Dr. Chris Rosinger,
describing the effect. He was the Bayer
researcher who managed the greenhouse
testing and first identified the potential
of triafamone.
Testing a thousand different
molecular variations
But it was a long road leading up to that
point: as much as ten years ago, Bayer
researchers in Japan turned all their attention to new variations of sulfonanilides, which had already proven effective
as herbicides. Their basic structure comprises two carbon- and nitrogen-based
rings linked by a chain containing carbon
and oxygen. Each ring has two additional molecular side groups. To find new,
highly effective substances, the Bayer
researchers altered various parts of the
molecule, developing a total of about
1,000 substances in the process. For instance, they changed the bridge between
the molecular rings, and switched the
halogens fluorine, bromine and iodine
on the side groups with one another,
replacing them with hydrogen atoms
or molecular groups containing carbon.
In Bayer CropScience’s greenhouses in
8
Bayer research 26 July 2014
Frankfurt, the different variations of the
active substance had to prove their ability
to combat a few typical rice weeds. “Four
out of five substances failed to clear this
first hurdle,” reports Rosinger. Active substances that did manage to pass these
initial tests were then tested on additional weeds. What sounds simple was no
easy task: “Finding a herbicide with such
a broad range of applications that it is
useful to as many rice farmers as possible is an extremely difficult task,” explains
Coralie van Breukelen-Groeneveld, global project leader at Bayer CropScience in
Monheim. The reason is that the weeds
growing in rice fields in Asia vary greatly from country to country and the level
of infestation is dependent on climate
and local conditions, i.e. the rice varieties planted and the irrigation methods
used. What’s more, every region has its
own method of cultivation: rice farmers
either sow the seeds directly by hand,
machine or airplane, or they transplant
seedlings by hand or mechanically from
a nursery box.
After just a year of screening, the researchers knew they had already found
the ideal molecule: the active substance
triafamone. “All other active substances,
some of which differed from triafamone
by only a single atom, had either a significantly narrower spectrum of activity
or were less selective,” the biochemist
relates. The process was extremely fast,
and surprisingly unequivocal: “It was
like winning the lottery. What are your
chances of getting all six numbers right?”
Rosinger says. Further greenhouse and
field testing, first in Frankfurt and then
worldwide, confirmed this initial success
and showed that the substance even
combats weeds which are resistant to
other herbicide classes.
“We also were able to demonstrate in
numerous studies that the acute toxicity
is rather low and the product poses no
health risks if it is used as recommended,” says van Breukelen-Groeneveld.
“If released into the environment, the
herbicide decomposes rapidly into metabolites.” This has been proven in innumerable tests with flooded rice fields,
different soil types and water management. The herbicide decomposes both
chemically and by microbial action. “In
most paddy soils, triafamone has a halflife of less than ten days,” van Breukelen­Groeneveld says.
Farmers are thrilled with the
results in their fields
Triafamone today has advanced far
beyond the trial phase: the herbicide
has already received approval in South
Korea and will be available there starting
in 2015. Market launches are scheduled
to follow soon in China, India and Japan.
“Whether it’s in granule or liquid form,
Rice AGRICULTURE
Bruce
Tolentino
“T he challenge of
climate change”
Dr. Bruce Tolentino is Deputy Director General of the
International Rice Research Institute (IRRI) in the
Philippines. research spoke with him about rice as a
staple food and the challenges of the future.
How important is rice?
Rice is the staple for half of the world’s population
– some 3.5 billion people, especially in Asia. Rice
consumption is also growing fast in the rest of the
world, particularly Africa.
Persevering researchers: the work on new crop protection agents by Bayer employees
such as Martina Mücke (photo above) and Goh Boon Yeong (below) includes tests on the
efficacy and safety of potential active ingredients, for example with biochemical analyses
of rice plants and weeds.
triafamone can be mixed with other
­Bayer herbicides to help expand the spectrum of activity and prevent resistance,”
Rosinger explains. The Bayer researchers
are not the only ones convinced of the
advantages of their multi-talented product. “Farmers are already delighted with
the results in our demonstration plots.
More than ­anything else, the active substance makes their work considerably
easier,” van Breukelen-Groeneveld says.
For example, triafamone can be applied in
all weather conditions and at any growing phase, even before the first weeds
sprout from the ground, for instance
during the first round of fertilization or
directly during planting.
For Japan, Bayer researchers have
even developed a machine that can plant
the seedlings and apply herbicides in a
single step. Similar systems are to follow
for China and India. “Also just one application should be enough,” Shirakura
emphasizes. That saves valuable time. But
despite all of these innovations, “rice still
does not grow all by itself,” says the researcher, who like so many people enjoys
rice as part of a healthy diet.
How healthy is rice?
Rice is very nutritious, but polished rice contains
low amounts of iron, zinc and vitamin A. Rice is
usually eaten in combination with other foods such
as fish, meat, and vegetables. However, the poorest
cannot afford much more than rice. Thus micronutrient deficiency is a serious problem among the
poor, especially women and children. So the IRRI is
working on rice varieties with higher iron, zinc, and
vitamin A contents. Diabetes is also associated with
rice-based diets so work on rice varieties with a low
glycemic index is also ongoing.
What are the biggest challenges in rice farming?
The impacts of climate change – floods, drought,
salinity and heat, and the increased volatility and
unpredictability in weather. Moreover, the population in developing countries continues to grow as
our natural resources dwindle.
What needs improvement?
R&D needs greater public funding to enable earlier
results, especially from research on rice varieties
that can better tolerate extreme weather, as well as
methods to help farmers cope with climate change,
including “alternate wetting and drying” (AWD),
which reduces water use and methane emissions.
www.research.bayer.com/rice
More information on the subject
Bayer research 26 July 2014
9
MATERIALS Solar Impulse
AVIATION PREPS NOVEL MATERIALS FOR EVERYDAY USE
Flying laboratory
Materials engineers develop many of their ideas initially for the aviation industry, but in doing so also stimulate
advancements in numerous other sectors, such as automotive and thermal insulation manufacturing. Premium
­materials from Bayer MaterialScience provide for greater efficiency and sustainability in these applications.
Flying may be the future, but harsh conditions prevail in aircraft
engineering: the materials are exposed to kerosene and aggressive de-icers, as well as extreme temperatures and intense UV
radiation. What’s more, engineers fight to eliminate every ounce
of weight they can from an aircraft. Nowhere are the demands
for developing new, innovative materials higher than in aviation. This is just as true for the new generation of ultra-high
capacity airliners as it is for the innovative aircraft project Solar
Impulse: the lightweight solar plane is to circumnavigate the
globe in 2015 powered solely by energy from the sun. On board
for the flight are premium materials from Bayer, which help to
stabilize the plane’s airframe and provide a durable coating for
its outer skin.
“Solar Impulse is like a catalyst for us. Through this project,
we were able to show just what our high-tech materials are
capable of under extreme conditions,” explains Dr. Bernd Rothe,
technical project manager for Solar Impulse at Bayer MaterialScience. Furthermore, the material ideas from Solar Impulse are
Bird’s-eye view: the first solar aircraft flying over San Francisco. Its successor is to circumnavigate the globe in 2015, powered only by the sun.
10
Bayer research 26 July 2014
Size comparison
Airbus A380-800
Solar Impulse 2
Cessna 400 (Corvalis)
Wingspan
79.8 meters
72 meters
11 meters
With the power of light: workers installing solar panels on the top of the wings.
For the plane to lift off on solar energy alone, it must be as lightweight as possible. This is where the high-tech materials from Bayer MaterialScience can help.
helping to advance materials for other markets and industries.
For example, Solar Impulse inspired new ideas in the field of
lightweight construction, which in turn help the automotive
industry, where metal and glass on doors and roofs are now
increasingly being replaced by plastics. As Dr. Martin Döbler, an
automotive expert at Bayer MaterialScience, explains, “Reducing
total weight by 100 kilograms cuts fuel consumption by half
a liter per 100 kilometers.” Bayer’s transparent polycarbonate
Makrolon™ is a particularly interesting alternative in this case,
and for more than just the cockpit window of Solar Impulse: it
can also significantly reduce weight in motor vehicles. As a crystal-clear plastic for automotive headlamps, it meets the strictest
optical requirements and weighs only half as much as glass.
Automotive developers are also turning to Makrolon™ for the
increasingly popular panorama roofs, because it is lightweight
and durable, but still a good insulator.
Photos: Jean Revillard/Rezo/Corbis (1), Jean Revillard/Rezo/Solar Impulse (1), private/Bayer AG (2)
High-performance foam for cockpits
and refrigerators
In private households, developments from the solar flier are
contributing to greater energy efficiency: “Even refrigerators
and freezers can benefit from Solar Impulse,” says Rothe. From
the hot Spanish sun to the subzero temperatures at an altitude
of 10,000 meters: the pilot must withstand extreme temperature fluctuations in the cockpit and therefore needs materials
with good insulating properties. The new Baytherm™ Microcell
insulation developed by Bayer experts can therefore be used to
insulate refrigerators, which are responsible for a major percentage of total energy consumption in modern households.
“The thermal conductivity of the rigid polyurethane foams used
inside should be as low as possible,” explains Dr. Reinhard Albers,
a technical insulation specialist at Bayer MaterialScience. “In the
case of Baytherm Microcell, we reduced the size of the pores in
the foam by 40 percent, which considerably increases insulation
performance.” The smaller the pores, the lower the thermal conductivity. Baytherm™ Microcell could significantly improve the
energy consumption of refrigerators and, thanks to its thinner
dimensions, make more room for milk, meat and vegetables.
Weight
569 tons
2.3 tons
1.6 tons
Maximum speed
958 km/h
140 km/h
435 km/h
Rail transport is another area that benefits from the flying laboratory. “The outer skin of a train, for instance, must be just as
durable as that of an aircraft,” explains Robert Reyer, a specialist
for transport and commercial vehicle coatings at Bayer MaterialScience. Aggressive cleaning agents are hard on the train coatings: “The coating really has to endure a lot when graffiti is
removed, from alkaline cleaning agents to those containing
phosphorous and hydrochloric acid,” Reyer says. Because a new
coating is expensive, the original must remain intact for as long
“Solar Impulse
is like a catalyst
for us.”
Dr. Bernd Rothe,
Bayer MaterialScience
as possible. Coating formulations from Bayer work so well in
this regard that the coating on Deutsche Bahn’s new ICx train
is made from Bayer raw materials.
All these examples show that the extreme demands in aviation help to improve existing products and test new ones. Although the Solar Impulse plane has yet to make its trip around
the world, for the experts at Bayer MaterialScience, it is the
journey that is the reward: they want to improve our everyday
lives, and their involvement in aviation will undoubtedly lead
to further solutions, because the harsh conditions prevailing in
aircraft engineering still pose a challenge.
Bayer research 26 July 2014
11
MATERIALS Solar Impulse
Wings
The wing covering 1 is a flexible, adhesive plastic textile. Thanks to
the Bayer raw materials in the extremely thin coating, the fabric is not
only extremely lightweight and light-stable, it is also waterproof and
wind-tight. These properties also prove valuable in model building and
kite construction, for example.
1
Frame
Rigid polyurethane foams provide a strong, insulating
but still lightweight outer shell for the frame 1 .
They also make the cockpit more stable and lightweight. The rigid foams offer optimum thermal
protection for the pilot and the equipment. These
same foams can also be used to improve insulation
in buildings.
The skin over the foam components 2 in Solar
Impulse 2 is a flexible, bonded plastic film. The
extremely thin Bayer coating on the film weatherproofs the surfaces with a minimum of weight. In
everyday applications, the Bayer coating is used to
improve model and kite building, as well as athletic
equipment, such as the 2014 World Cup soccer ball
from adidas.
2
1
12
Bayer research 26 July 2014
“Lightweight and
fuel-saving”
Professor Heinz Voggenreiter is Director of the Institute of
Materials Research and the Institute of Structures and Design
at DLR, Germany’s center for aerospace research. research
spoke with him about the use of new materials in aviation.
How will materials develop in the future?
Why are high-tech materials so important in aviation?
New materials can greatly reduce the weight of an aircraft and
consequently also fuel consumption and emissions. For example, carbon fiber reinforced plastics, or CFRPs for short, make
the fuselage and wings up to 20 percent lighter. Aluminum
that incorporates lithium and scandium is another material
that supports lightweight and low-cost structural design.
3
2
Heinz
Voggenreiter
The capabilities of new fiber composites will continue to rise
thanks to the use of increasingly high-quality fibers and design
principles. Aluminum alloys will be stronger and more cost-­
efficient in the future, and eventually pose serious competition
for carbon fiber composites. By concentrating on hybrid structures, however, we can exploit the advantages of both materials. Of course, we must continue to automate our production
technologies at the same time.
5
1
4
Cockpit
Experts from Bayer MaterialScience developed and built the
entire cockpit shell 1 for Solar Impulse 2.
The cockpit door 2 must meet particularly high requirements
on insulation and stability. It is therefore made of the special
rigid polyurethane foam Baytherm™ Microcell. This insulating
material is normally used to reduce the energy consumption of
refrigerators. Carbon fibers combined with polyurethane resin
make for a uniquely strong, stiff but very lightweight hinge 3
for opening the door. In the automotive industry, this special
material could soon also be used in the chassis and doors.
The cockpit coating 4 made of Bayer raw materials is
extremely weather resistant, but also very thin, meaning it
­further minimizes the weight of Solar Impulse 2.
The polycarbonate cockpit window 5 is lighter than glass
and a better insulator. What’s more, the special plastic makes
the window highly scratch and weather resistant. With its
unique properties, this material is suitable for headlights and
roofs in the automotive industry, as well as for CDs, DVDs and
Blu-ray discs.
www.research.bayer.com/solar-impulse
More information on this subject
Bayer research 26 July 2014
13
COLLABORATING WITH TOP INTERNATIONAL
­RESEARCHERS ON NEW THERAPEUTIC OPTIONS
Networking for
better healthcare
All around the world, pharmaceutical researchers and patients are united by a huge mission:
the search for powerful treatments capable of
prolonging life and offering completely new therapeutic options. Bayer experts are therefore cooperating with top scientists from around the globe,
for example the United States and China. They
want to jointly develop creative approaches for
new drug products to treat, for example, cancer,
cardiovascular diseases and lung diseases. ­Bayer‘s
scientists hope that this combined innovative
strength will be able to enhance people’s lives.
Structural elucidation: to ensure that drug products can dock at a specific point in the body, scientists have to understand the precise
­structure of the ­target. They can then develop an active substance that binds at this exact site. Bayer colleagues from Structural Biology
like Tina Stromeyer therefore support the scientists by investigating crystal structures under the microscope.
14
Bayer research 26 July 2014
Photos: Peter Ginter/Bayer AG (9), Hans Scherhaufer/Bayer AG (1), Xinting Qi/Bayer AG (1), Paul Zinken/dpa Picture-Alliance (1), private/Bayer AG (1), Matthias Sandmann/Bayer AG (1)
Cover story MEDICINE
Bayer research 26 July 2014
15
Cell comparison: the tiniest changes to the genetic material can make the difference between a healthy cell and a cancer cell.
Finding these genes is the responsibility of scientists like Cassandra Elie from the Broad Institute in Boston, USA, who use state-ofthe-art technologies to analyze numerous tumor genomes from patients and compare them with the genomes of healthy cells
taken from the same patients.
16
Bayer research 26 July 2014
Cover story MEDICINE
Pharmaceutical research is a risky business: innovative ideas can
crash and burn on their way to becoming a new drug - but they
might just hit the bullseye and enable patients to live a better
life. The latter include individualized cancer treatments, for example, or innovative active ingredients for patients with hemophilia that might no longer have to be injected. Bayer scientists
are among the researchers searching for these innovations, in
many cases arising on the very fringes of our constantly expanding medical knowledge. “To really set new therapeutic standards
or help patients for whom we don’t yet have treatments, we need
medical breakthroughs,” explains Professor Andreas Busch, Head
of Global Drug Discovery at Bayer HealthCare.
The search for new paths to the limits of the known world
– in the most varied of disciplines – is best traveled together in
a network with top scientists from all over the world. The need
is great. Take lung cancer, for example: “Some lung cancer patients have a mutation in a specific gene, and we can help these
patients. But for others, however, there’s not much we can do.
It depends on where precisely the gene is mutated,” explains
Dr. Matthew Meyerson, a pathologist at the Dana-Farber Cancer
Institute in Boston, USA. Meyerson played a leading role in the
development of two therapies for lung cancer patients, and is
now collaborating with Bayer researchers to find new approaches. “Our knowledge of the specific characteristics of many tumor
cells is now so extensive that we can transform it into breakthrough innovations for patients with different types of cancer if
we join forces to work together,” explains Dr. James E. Bradner, an
oncologist at the Dana-Farber Cancer Institute. He and Meyerson
are also each in charge of their own research laboratories at the
globally renowned Broad Institute, Boston, USA. Bayer recently
began collaborating with this important cooperation partner in
the search for new cancer treatments.
Cooperation for new cancer treatments: intensive
dialog with researchers from the Broad Institute
The Broad Institute unites scientists from Harvard, the Massachusetts Institute of Technology (MIT) and several hospitals under one roof and is a pioneer in the field of oncogenomics. For
example, the scientists are searching for gene mutations that
are typical for various types of cancer and could therefore offer
targets for new treatments. To find such genes, the researchers
employ state-of-the-art technology to analyze multiple tumor
genomes from patients and then compare them with genomes
from healthy cells of the same patients. “That allows us to identify precisely the points at which the cancer cells differ from
normal cells,” explains Dr. Barbara Nicke, a biologist at Bayer
HealthCare. Many of the pathological cells in genetic material
can be divided into two groups – mutations in oncogenes that
promote cell reproduction and mutations in what are called tumor suppressor genes which are then no longer able to halt cell
growth (see infographic on page 19).
Once these cancer drivers have been identified, Nicke and her
colleagues get working to experimentally investigate the significance of these genes in the laboratory. Bayer scientists are now
able to exchange notes with the experts at the Broad Institute
Transatlantic dialog: Dr. Florian Pühler from Bayer (left) is responsible for
accompanying the collaboration between Bayer and the Broad Institute in
­Boston and is therefore in close contact with scientist Dr. Matthew Meyerson
from the Institute.
and thus benefit from their experiences. And their combined
knowledge is also useful when it comes to selecting potential
development candidates later on: “Our substance libraries complement each other well and open up completely new opportunities for patients who currently have no treatments available,”
says Dr. Florian Pühler, Alliance Manager at Bayer HealthCare,
who is based in Boston to support the collaboration locally.
While many of the biological mechanisms involved in cancer
research are already understood in great detail, the mechanisms
in other areas have still to be discovered. “That’s why we often
collaborate with outstanding scientists from academic research
institutions,” explains Dr. Chris Haskell, Head of the Bayer Health-
“To help patients
for whom we don’t
yet have treatments,
we need medical
breakthroughs.”
Professor Andreas Busch,
Bayer HealthCare
Bayer research 26 July 2014
17
DNA carries valuable information: state-of-the-art analysis robots like the ones used by the Broad Institute’s sequencing department can reveal the
secrets of a patient’s DNA and help precisely pinpoint the areas in the tumor genome that distinguish the cancer cells from normal cells. This allows
researchers like Kendra West and Karen Israel (left to right) to identify relevant tumor drivers for further studies.
Care Science Hub in San Francisco, USA. An expert group headed
by Bayer scientist Dr. Ye Jin and Professor Charles Craik from the
Department of Pharmaceutical Chemistry at the University of
California, San Francisco (UCSF) has investigated a mechanism
used by the innate human immune system to protect the body
against foreign objects and intruders: NETosis. In the event of an
Enhancing the quality of
life for hemophiliacs
Hemophilia is a condition that mainly affects men. Sufferers
lack a specific factor in their blood coagulation and therefore
have a tendency to bleed severely, which can have dangerous
consequences. Approximately 400,000 people around the world
suffer from hemophilia A. The condition cannot be cured but it
is now possible to administer the missing factor intravenously.
However, the relevant protein breaks down in blood over time,
so it has to be administered at regular intervals, several times a
week. Bayer scientists are currently working on extending the
duration of action of the coagulation factor in blood to improve
the quality of life for patients.
infection, specific cells in the immune system called neutrophil
granulocytes release a sort of spider’s web of DNA that becomes
loaded with antimicrobials. This net traps microorganisms and
is capable of destroying them.
But as useful as this mechanism is, “an increasing number
of inflammatory and autoimmune disorders are known to trigger an excessive NETosis response, destroying adjacent cells or
even causing thrombosis,” says Jin, explaining the unwanted side
effects. Such disorders have also been observed in rheumatoid
arthritis and lung diseases such as cystic fibrosis or allergic asthma. With the help of the expertise of Craik’s team, Jin and her
colleagues have identified and analyzed the neutrophil granulocytes’ main weapons: “Certain enzymes known as proteases appear to play a key role in the NETosis function and could
therefore be attractive diagnostic markers as well as a potential
target for new therapies,” says Jin. NETosis may also be significant in a variety of cardiovascular diseases. Bayer scientists are
therefore working together with their experienced colleagues
from UCSF in the search for approaches to regulate NETosis.
They have already identified four key proteases that are now
being further investigated. “The project shows how knowledge
can be gained if top scientists from both academia and industry
cooperate closely,” says Busch. After all, without the joint efforts
and knowledge contributed by both sides – UCSF and Bayer – the
project probably would not have been so successful: “We have a
lot of experience and the appropriate technologies for analyzing
proteases and their activities,” explains Craik. His team was able
Continued on page 21. 18
Bayer research 26 July 2014
Cover story
MEDICINE
“Research for patients”
Dr. Stuart Schreiber is one of the four founding members of the
Broad Institute, Boston, USA. The renowned non-profit research
institute unites outstanding scientists and oncologists under
one roof and has comprehensive expertise in tumor biology
and cancer medicine.
Which projects in the area of cancer research do you regard as
particularly promising?
Cancer cells are robust and extremely hardy. We are gradually
learning that tumors can develop like organs. Precisely this
cell differentiation process is a target for cancer treatments,
which makes it very interesting. There are also a number of new
targets in tumor therapy known as epigenetic targets that I
believe are very promising.
What does the collaboration between Bayer and the Broad
Institute mean to you?
We at the Broad Institute are primarily focused on early biomedical research. Bayer is the first partner we have had that
Stuart
Schreiber
has a lot of experience in transforming early-stage developments into medications that are approved for patients. There
are many new aspects here for us, and it’s very exciting to be
traveling down this road together with Bayer.
How will patients benefit from the research being conducted at
the Broad Institute in future?
Our therapy development is strongly focused on patient
needs and is closely linked to human biology and the individual
characteristics of the cancer patients themselves. We believe
that we can develop new and efficient drug products much
more quickly.
Cancer growth: genes as both the brake
and gas pedals
Cancer always begins with changes to the DNA. While a single mutation does not generally lead to cancer, scientists have now identified
two important classes of genes that are directly associated with a loss of growth control. Changes to oncogenes accelerate cell division,
mutated tumor suppressor genes can no longer effectively halt cell growth.
Mutations in oncogenes are like a
jammed gas pedal in a car: they
increase the speed of cell division.
Mutation of a gene
into an oncogene
Healthy cell
Cancer cells divide and grow into a tumor.
Mutation in a tumor
suppressor gene
Mutations in tumor suppressor genes
behave like defective brakes: the cells
continue to divide uncontrollably.
Bayer research 26 July 2014
19
Active ingredient purification at laboratory scale: new drug products manufactured using biotechnology are produced in mammalian cells.
Katherine Tran, a protein researcher at Bayer in San Francisco, USA, labels a plastic bag containing a culture medium in which the precious
cells will grow and from which the active ingredients can ultimately be derived by means of purification.
20
Bayer research 26 July 2014
Cover story MEDICINE
to learn from Bayer how this knowledge can ultimately be used
in pharmaceutical research and integrated into a project plan.
New projects like NETosis research can be risky for all involved parties. On the one hand, they could generate an innovative therapeutic approach, but they could just as likely lead
to a dead end. “But if you want to achieve breakthroughs, you
mustn’t be afraid of failure. Innovations always involve some
risk – that’s something we can and have to consciously factor
in,” explains Busch. The NETosis project was likewise divided into different risk stages. After an initial experimental phase, the
results were evaluated by both sides and the decision was taken
to continue the project.
Good mix: high-risk projects involving new
technologies and concrete research projects
Collaborations between universities and industry can be extremely successful, which is also being demonstrated by the strategic
partnerships with top scientists on the other side of the planet in China. “We’re relying on a good mix of more high-risk start-up
projects involving new technologies, for example, and concrete
research projects,” explains Dr. Jing-Shan Jennifer Hu, Head of
the Bayer HealthCare Innovation Center China in Beijing. Here,
a group headed by Professor Hilmar Weinmann, Division Head
of Medicinal Chemistry at Bayer HealthCare in Berlin, Germany,
is working together with Professor Xiaoyu Li from Peking University on setting up DNA-encoded substance libraries. Bayer
researchers will then be able to use these in the future to search
for new starting points for therapeutic molecules thanks to a
highly efficient technology.
What is special about this technology is that each tiny molecule is labeled with a kind of barcode – a DNA fragment. “That
means that we will require less effort in substance logistics and
Helpful robots: before promising protein crystals can be investigated, they first
have to be manufactured. To this end, Bayer research assistant Tina Stromeyer
fills a pipetting robot with a protein crystallization solution. Numerous tests
can then be run in parallel.
will be able to test extremely large substance libraries with great
efficiency,” explains Weinmann. If the pilot project continues in
such a promising fashion, the technology could also be applied
elsewhere, and could become an important additional method
in the future, both in the search for new molecules in cancer
therapy and for other diseases. However, the project would not
have been viable without the chemical expertise from Peking
“Quick success”
Professor Karl Max Einhäupl is a neurologist and Chairman of
the Executive Board of Europe’s largest university hospital: the
Charité in Berlin employs 16,000 nurses, carers, doctors and
scientists who attend closely to their patients’ needs.
Which treatments are patients pinning their hopes on in
­particular at present?
Patients want to be able to benefit from new treatments as
quickly as possible and they should be available at affordable
prices.
How do patients judge whether new treatments are a success
or not?
They assess the success of their treatment on the basis of the
ratio of its efficacy to its side effects. Patients are increasingly well informed, and in more and more cases they consider
Karl Max
Einhäupl
whether they wish to expose themselves to the potential risks
before undergoing treatment.
In your opinion, in which clinical picture has the greatest
­progress been achieved in recent years?
As a neurologist, I can confirm that my field has developed from a
relatively limited discipline into one in which therapeutic options
are now available. We are seeing considerable progress in diseases
such as Parkinson’s disease, dystonia, epilepsy, multiple sclerosis
and other severe infections of the central nervous system.
Bayer research 26 July 2014
21
High-level partnership: Bayer scientist Dr. Ye Jin and Professor
Charles S. Craik from the University of California, San Francisco
(photo below, from left) are investigating a still largely unknown
mechanism of the human immune system, with the support of
their colleagues such as Efrat Harel (photo, above).
currently in the development phase and could mean that patients
suffering from hemophilia may no longer have to inject coagulation factors in the future.
But the enzyme – a protease – is tricky. “To inhibit the targeted function, we need a molecule that fits perfectly into its
3D structure – and nowhere else,” says Dr. Ursula Egner, Head
of Structural Biology at Bayer HealthCare. Once a potential drug
candidate has been found, it has to be further optimized. For
this, Schäfer and her team produce 3D models of crystal structures on the computer. First, however, the Bayer experts have to
understand the structures of the two molecules and how they
bind to one another. “We get this information from the crystal
structures of the respective molecular complexes,” says Schäfer.
University: Li’s team generated both the DNA codes and the final
molecule library. “This dialog with other experts and renowned
institutions strengthens the spirit of invention in our teams, inspires lateral thinking and thus paves the way for new technologies and treatments,” says Busch.
The value of this approach has also been demonstrated in the
work to develop a new active ingredient for hemophilia patients;
here too, cooperative input from experienced experts has proved
its worth. “We’re looking for a substance that prevents excessive
blood loss and can be taken in tablet form,” explains Dr. Martina
Schäfer, a structural biologist at Bayer HealthCare. The researchers’ idea is to block a specific enzyme that plays a key role in
fibrinolysis, the process involved in dissolving blood clots. “If we
can successfully inhibit this enzyme, we will be able to promote
wound healing, a mechanism which no longer works correctly
in many hemophilia patients,” explains Schäfer. The substance is
Each molecular complex involves different
­challenges – and necessitates new partners
Investigating the chemical compounds requires a great deal of
skill and experience with different solvents and other chemicals,
because every molecular complex is different and involves new
challenges. The Bayer experts are therefore constantly searching
for different partners with exceptional expertise. In the hemophilia project, they found the ideal partner in Professor Haitao Li
from Tsinghua University in Beijing. “Li’s team generated valuable crystal structures for us, and used a substance for protein
purification that we now use routinely ourselves,” says Dr. Naomi Barak, Alliance Manager at the Bayer HealthCare Innovation
Center China and responsible for the collaboration with Tsinghua
University. But Li also learned a lot from the colleagues at Bayer
Continued on page 24. 22
Bayer research 26 July 2014
Cover story MEDICINE
Bayer CoLaborator:
­inspiring environment
Success through teamwork: Bayer scientists Dr. Anke MüllerFahrnow and Dr. Ursula Egner (left to right) are relying on the
crystallography expertise of specialist Professor Haitao Li from
Tsinghua University. He in turn is gaining an insight into the work
of a pharmaceutical corporation and benefits from the researchers’ wealth of experience.
The CoLaborator concept shows how individual companies
can benefit from a scientific network: the start-up company
Xcell Biosciences, for example, rented premises on Bayer’s
Mission Bay site in California close to Bayer HealthCare’s
own research labs. “Their technology looks very promising to
us,” explains Dr. Chris Haskell, Head of the U.S. Science Hub.
The “Avatar” platform developed by Xcell Biosciences aims
to very specifically analyze a patient’s cancer cells: the cancer specialists plan to use blood samples to determine which
drug products would be appropriate for a specific tumor.
“We’ve already built up and consolidated our scientific network in these innovative surroundings,” confirms Brian Feth,
founder of Xcell Biosciences. There are also opportunities for
young life science companies to rent laboratory and office
space in the immediate vicinity of Bayer research departments in Berlin. The aim is to promote scientific dialog above
and beyond company boundaries.
From molecule to medicine – a marathon of tests
The road from a promising active ingredient to the drug product in the pharmacy is like a marathon – a race that demands not only outstanding partners but also a great deal of perseverance. Once Bayer researchers have identified a promising candidate for a new drug product, it undergoes numerous studies, which can take approximately ten years and often involves investments of more than EUR 1 billion.
Active ingredient discovery
Active ingredient
research
10,000
investigational substances
Preclinical
Clinical testing
Lab and animal
tests
Phase I: 20-100 healthy volunteers
T olerability, pharmacokinetics / pharmacodynamics
Phase II:100-500 patients
­Safety, efficacy (dose-finding)
Phase III:1,000-10,000 patients
­Efficacy, safety
< 250
investigational
substances
Testing/regulatory Phase IV studies
approval
(up to 2 years)
(>2 years)
<5
investigational substances
1 drug product
granted regulatory
approval by the
authorities
> EUR 1 billion
0
2
4
6
8
10
12
years
Bayer research 26 July 2014
23
MEDICINE Cover story
INTERVIEW WITH DR. KEMAL MALIK
“Freedom to
innovate”
Dr. Kemal Malik (51) has been a member of the Board of Management of Bayer AG since February 1, 2014, and the Board
spokesman for Innovation since May 1, 2014. After practicing
as a physician, Malik entered the pharmaceutical industry
and in 1995 was appointed Head of Bayer’s Metabolism and
Oncology therapeutic areas in the Europe region. This was
followed by further assignments as Head of Medical Development and then as Head of Global Development at Bayer
HealthCare. Malik spoke with research about key drivers of
innovation at Bayer and other topics.
Who dares, wins: Bayer scientist Dr. Ye Jin suggested starting work on a
­completely new project. Her courage paid off.
as well: “I’ve gained a valuable insight into active substance development and learned a lot about new hemophilia treatments,”
says Li, who has been working mainly in structural epigenetics
research.
Focus on benefits for the patients: further
strengthening the global innovative power
in fringe areas as well
Regardless of which research area the cooperation partners are
operating in – “the focus is always on the direct benefit for the
patients,” says Busch. Particularly important for the future for
him will be to make sure that the company does not concentrate
too closely on individual projects. “We have to keep an eye on
the fringe areas as well so that we can find spaces for potential
new treatments,” explains Busch. The hemophilia project likewise
has potential that extends far beyond a drug product only for
hemophilia patients: “A second feasible application, for example,
could be a tablet for women who have heavy menstrual bleeding,”
says Bayer scientist Schäfer. Yet another indication could be the
prevention of heavy blood loss during organ transplantation.
So innovative power is not something that is going to run
out at Bayer any time soon. To reach patients all over the world,
Bayer scientists are committed to collaborating with renowned
partners all around the globe, venturing together with them into
new scientific terrain.
www.research.bayer.com/network-medicine
More information on this subject
24
Bayer research 26 July 2014
Mr. Malik, Bayer’s scientists conduct leading-edge research
at the interfaces between the life science fields. How important is this research for the company?
There’s no question that innovation is vital for every
company. There’s a simple saying in the business world:
innovate or die. Bayer is a world-class innovation company. Without science – that is to say, without research
and development – we will not be able to meet the challenges currently facing our planet. Innovations in the life
sciences – in other words the health care and agriculture
businesses – safeguard the future. And not just the future
of our company but also, in more global terms, that of our
planet’s entire population. Bayer anticipates long-term
growth stimulus from interdisciplinary research in the
­areas of human, animal and plant health. We are convinced
that considerable research synergies exist here. Overall we
intend to increase research and development expenditures
in the Bayer Group to some EUR 3.5 billion in 2014. The
key part is that innovation is the fundamental basis for the
sustainability of our company. We have just celebrated
our 150th anniversary – innovation will ensure we can celebrate another 150 years.
Is investment in leading-edge research alone sufficient to
guarantee innovation capability?
Well, groundbreaking developments are not just a result
of spending money. We have seen that across the industry.
However we do need to ensure that we spent adequately to
sustain our pipeline. In addition, innovation can only occur
if we bring together the most creative minds and researchers with ideas and a passion for what they do. That’s why
we are steadily expanding our network of outstanding research partners from science and industry worldwide, and
with incubators, crowdsourcing and our innovation centers
in Europe, the United States and Asia, we are tapping into
INTERVIEW
as is clear from our research and development spending in
the Pharmaceuticals segment, where we invested EUR 1.7
billion in 2013. Our progress here speaks for itself: in the
recent past we have brought five innovative medicines to
market, including anticoagulants and new cancer drugs.
What’s more, we have chosen five promising active substance candidates from our well-stocked research pipeline
for accelerated development. We want these substances
to be ready for a decision on the transition to Phase III
clinical development by the end of 2015.
What characterizes a highly innovative company
in your view?
This is a fascinating question. When one looks at truly
innovative companies (which I think we are) then there are
certain characteristics that are common to them all. The
first is a commitment to innovation at the highest levels in
the organization. In addition, they have a huge portfolio of
ideas – and they know how to manage and prioritize these
ideas. A key part is they have a strong and laser-focused
customer insight. Finally, they have a corporate culture
that appreciates innovation. The active development of an
innovation culture is key – the desire and passion to take
the necessary actions.
Sights set on innovation: Dr. Kemal Malik is a member of the
Bayer AG Board of Management. He is responsible for Innovation
and the North and Latin America regions.
external innovation potential in line with the concept of
open innovation. I believe we have an obligation to apply
this combined knowledge to achieve the maximum possible gain for people around the world and also ensure the
sustainability of our organization.
Bayer is investing more than US$14 billion in non-prescription medicines alone with the acquisition of the consumer care business of U.S. pharmaceutical company
Merck & Co., Inc. Doesn’t this contradict your aim of being a world-class innovation company?
No. Certainly, this acquisition is a milestone for our company toward our goal of achieving global market leadership in the non-prescription medicines business. And
incidentally, there are innovations that meet the needs of
patients in this segment too. But at the same time, the
transaction has enabled us to expand our development
options in the field of cardiovascular therapies, as the
agreement includes a strategic collaboration in the field
of soluble guanylate cyclases, otherwise known as sGC
modulators. Cardiovascular disease is one of the most
important therapeutic areas in which there is still a high
level of medical need. This collaboration gives us even
greater opportunities to develop new medicines for patients. And we are not going to stop investing in research,
Patients, farmers and customers want new products that
make life better or easier. Apart from this, what are the
other drivers of innovation?
In my view, one of the next big drivers of innovation will
be digitalization. It’s often called the “third revolution” after the agrarian and industrial revolutions - the so-called
third industrial revolution – and it will affect all areas
of life. The “digital world” is becoming a new business
environment and opening up perspectives – from data
collection through data analysis to data sharing and new
communication and interaction possibilities. The communications and logistics fields are already well advanced
in their adoption, but there is still a lot of development
potential in the pharmaceutical and chemical industries:
for example, digitalization enables completely new ways
of helping patients cope better with everyday life, to
understand their disease and it allows their healthcare
professionals to monitor their well-being through the use
of new tools such as healthcare apps. At the same time, it
also provides opportunities for agriculture: by combining
digital services and integrated agricultural solutions, for
example, we can further enhance the services we provide,
increase yields and thus increase our contribution to safeguarding food supplies.
Mr. Malik, let’s close with a personal question: where do
you find new and creative approaches?
I usually come up with ideas when I’m alone: on walks, on
the golf course or when I’m riding my bike. My motto is
“make a difference”, and I’ve always lived my life according
to this maxim. And I am convinced that the innovations
from Bayer will make a difference to the world.
Bayer research 26 July 2014
25
NEW VARIETY OF CANOLA REDUCES CROP LOSSES IN THE FIELD
Strong seed pods
Canola seed pods contain a valuable freight: the black seeds inside are pressed to extract an oil that is in global
demand. However, if the seed pods open prematurely in the field, many of the seeds end up on the ground, resulting in
lost yield. Researchers at Bayer CropScience have now developed a variety of canola with especially robust seed pods
which are increasing yields for farmers in Canada.
Precious pearls: to make sure that as many of the black, oily canola seeds as possible can be harvested, Bayer researchers are developing
robust seed pods.
26
Bayer research 26 July 2014
Canola AGRICULTURE
Photos: Bernhard Moll/Bayer AG (2), Dirk Hansen/Bayer AG (1), Matthias Sandmann/Bayer AG (1), Peter Ginter/Bayer AG (1), private/Bayer AG (2), Miglbauer/agrar-press (1), Krick/agrar-press (1)
All for the yellow flowers: Dr. Bart Lambert (photo, right) and his team are developing canola varieties with stronger seed pods. The plant experts
use state-of-the-art biotechnology to selectively adjust the stability of the canola pods, thereby preventing the seeds from spoiling before the
harvest.
For a plant, getting started in life is no
easy task: in order for seeds to become
productive plants, the delicate seedlings
must first break through a hard shell.
Mother Nature makes the joints in seeds
especially thin for precisely this reason.
They split open more easily, making it
possible for the sprouts inside to germinate. Canola pods have exactly this type
of “pre-set breaking point” as well. The
pods are composed of two halves, also
known as valves, firmly held together by
a specialized tissue. When the pod is ripe,
the tissue disintegrates – the pod splits
open, releasing the black seeds inside.
It’s a natural process, but one that can
drive canola farmers to despair. “If the
ripe plants are buffeted by strong winds,
for instance, the pods break open in the
field and yield is lost. The seeds fall to the
ground and can then no longer be used,”
explains Dr. Bart Lambert, who was previously responsible for global canola trait
research at Bayer CropScience. “In 2012,
for example, heavy summer storms ruined
a large part of the harvest for farmers in
Canada,” continues Lambert. Canada is
one of the world’s largest growing regions
for spring swede rape (known as cano-
la in Canada). Canola, which is sown in
May and harvested in August, is especially
common in Canada and is the country’s
most valuable crop.
At present, canola growers manage
seed loss by swathing – cutting the plants
down in windrows three weeks before
they become completely ripe. The canola
plants then ripen on the ground.
Improving shattering resistance
of canola pods to protect yields
This less-than-ideal practice is a necessity,
even though it is associated with disadvantages for farmers. It requires an extra
round of field work prior to harvest and,
in addition, swathing the plants cuts off
their supply of nutrients so the seed pods
do not fully ripen and the seeds contain
less oil as a result. Yet it is precisely this
oil that is in such demand. Canola oil
is popular worldwide, in particular as a
cooking oil, because of the high proportion of healthy, unsaturated fatty acids it
contains. Canola oil also plays a role in
very different areas, such as the production of biofuels. It likewise serves as an
important raw material in the making of
varnishes, paints and lubricants. Canada
alone exported 7.1 million tons of canola
seed worldwide in 2013.
Lambert’s team has now developed
a new solution that protects the plant’s
valuable oil-rich seeds: a type of canola
with a more robust seed pod. In order to
accomplish this, the biotechnology specialists specifically modified the characteristics of the pod’s pre-set breaking
point, which botanists refer to as the
dehiscence zone. It was no easy task:
“The formation of this brittle tissue is
controlled by several different genes,”
explains Benjamin Laga, who led the pod
7.1
million tons
Canada exported
7.1 million tons of canola
seed in 2013.
Source: Canola Council of Canada 2013 Annual Report
Bayer research 26 July 2014
27
AGRICULTURE
Canola
Pod check: Kevin and Herbert Serfas (photo left, right
to left) assess the canola plants at Ironsprings Farm in
Canada. The ripe, black seeds contain large amounts of
canola oil (photo right).
Strategy for shatter-resistant pods
The stability of the canola pods can be adjusted using reverse genetics. Researchers generate chemical changes (mutations) in the
genotype. The candidates with an IND mutation are backcrossed with the original plant. The canola plants that result from this cross
have stronger seed pods. The seeds stay in the pod and do not fall out when buffeted by the wind.
Undesirable
mutations in
other sections of
the genome
Mutagenesis
Canola
genome
with active
IND gene
As a result of backcrossing and
selection, only the desirable mutation in the IND gene remains.
Desirable
mutation
in the IND
gene
Desirable
mutation in
the IND gene
Plant
Strong wind
Strong wind
Cross-section
of a canola pod
Dehiscence zone
= pre-set breaking
point
28
Cross-section
of a canola pod
Seeds
Bayer research 26 July 2014
Seeds fall out
of the pod
Dehiscence zone no
longer present
Seeds
Seeds remain
in the pod
Delicate seedlings: the characteristics of the young canola plants (photo above) are
comprehensively examined in laboratory tests and field trials. This is the first point
at which scientists can tell whether the plants carry all of the desired characteristics. Bart Lambert and Benjamin Laga (photo right, left to right) monitor the canola
plants’ growth.
shatter reduction program. The team
of researchers focused on one of them:
the INDEHISCENT gene, or IND for short.
“When this gene stops working,” says
Laga, “a pre-set breaking point does not
form. The valves of the seed pod grow
firmly together.”
seed pods would not break open in the
wind on the field – but they would also
resist opening by farmers using conventional harvesting methods.
Using reverse genetics and
backcrossing to create shatterproof seed pods
After several modification attempts, however, the scientists were able to custom
tailor the strength of the seed pods. The
key to their success: reverse genetics. It
begins directly in the DNA – the genotype
of the canola plant. The researchers first
used a chemical technique to make small
random changes, known as mutations,
across the entire DNA. From among the
thousands of randomly changed plant
genomes, they then selected those with
a mutation in the IND gene.
This change is not visible in the seeds,
however. The biotechnology specialists
therefore had to analyze the genotype by
amplifying and sequencing the IND section of the various genes. When this was
compared with the original gene sequence,
researchers could tell which canola genes
had promising IND gene mutations. Using
this method, the specialists at Bayer were
able to reduce the huge pool of possibilities to some 20 candidates.
Unwanted mutations also occurred
outside of the IND gene, however. Researchers therefore had to eliminate these
by repeatedly backcrossing the new plants
with the original unmodified one. The re-
Nature didn’t just hand this success to the
scientists on a silver platter, however. It
took more than ten years of research in
laboratories, greenhouses and fields. For
example, the scientists blocked the IND
gene with ribonucleic acid interference,
a natural mechanism that shuts down
targeted genes in biological cells. This
method is also used by plant and animal
cells to protect themselves against threats
such as dangerous viruses. Ribonucleic
acid – known as RNA for short – serves
as a mediator between genes and protein,
translating the information from the genotype into proteins. In order to switch off
the IND gene, Lambert and his team first
developed a tailor-made sequence that
fits precisely onto the RNA of the unwanted IND gene – like a Velcro fastener – and completely interrupts the chain
of information. This approach worked
well – a little too well, in fact. “The seed
pods were so strong that we were almost
unable to open them,” says Lambert. The
From technical concept to a
commercial trait
sulting seeds could then leave the laboratories and greenhouses. They were planted
in Belgium and Canada as part of the field
trials phase. It was an exciting moment for
the scientists. The field trials took three
years. In each season, the researchers had
to wait patiently until the plants were ripe.
Oily delight
Canola oil is widely used on salads, for frying and
in margarine. Just a few decades ago, however, this
vegetable oil played only a minor role in the food
industry. The reason: it contained bitter substances
such as erucic acid. In 1974, Canadian plant researchers succeeded in breeding an oilseed rape plant
with significantly fewer bitter constituents and thus
made canola oil palatable.
The seed pods on some plants were very
difficult to open. Others were more promising and were put into the next phase of
cultivation. In this way, the scientists were
able to continuously reduce the selection –
until one plant had the characteristics they
were looking for. “Its seed pods were not
too robust, but not too easy to open either,”
says Laga.
But the scientists wanted more than
just shatter-resistant pods, however, so
they transferred and tested the final mu-
Bayer research 26 July 2014
29
AGRICULTURE Canola
Golden prospects: at the Monheim research site, Bayer CropScience scientists investigate how the new canola varieties grow in the greenhouse and in
field tests (photo left), and take tissue samples for detailed analysis in the laboratory (photo right).
tant IND gene in hybrid canola. Hybrids
are generally more productive and more
resistant to stress than open-pollinated
varieties – an effect experts refer to as
­heterosis. The result: hybrid canola with
lots of large, good-quality seeds that
remain safely in their seed pods until
harvest.
A first hybrid is now available to farmers in Canada under the name ­InVigor™
L140P. This is a reason to celebrate for
researchers and for farmers as well: the
variety carries the first yield trait created
with this method to be commercialized
in the history of Bayer CropScience. Canadian farmers can now be more relaxed
during harvesting time as they do not
have to fear significant seed loss when
the weather gets worse and the wind
grows stronger. They also have the option
to harvest their canola fields at just the
right time without having to swath them
first. This gives the plants enough time
to ripen. “They form better-quality seeds
and fuller seed pods,” explains Lambert,
“which in turn yields larger harvests.” The
The most important canola-growing nations
The world map shows the five countries that produced the largest quantities of canola
(in millions of tons) in 2012. The biggest producer was Canada, with 15.4 million tons.
4.8 Germany
15.4
Canada
5.5
France
6.8
India
14.0
China
scientists at Bayer are not resting on their
laurels, however. “Canola is a relatively
young crop plant. So there is still a lot
of potential for improvement here,” says
Lambert. Canola has only been commercially grown since the 1970s – and has
already enjoyed a meteoric career.
Resistance to fungal infections:
no end to the ideas for new
canola varieties
The crop is now the most important oil
seed after soy. “We want to gradually
continue improving the canola plant,”
says Lambert. The mutant IND gene for
strong seed pods is now being incorporated into other canola hybrids for the
European market. Bayer CropScience
Trait R
­ esearch teams are a­ lso working on
further increasing yields by optimizing
the supply of nutrients to the pods. These
plant characteristics can then be combined by conventional breeding with resistances to dangerous fungal infections,
for instance. “This enables regionally
tailored varieties that farmers can use to
respond to the special challenges in their
cultivation area in a very individual way,”
says Lambert.
www.research.bayer.com/canola
Source: FAOSTAT
30
Bayer research 26 July 2014
Further information on this topic
Clinical trials MEDICINE
TRANSPARENCY INITIATIVE: BAYER DISCLOSES DATA FROM CLINICAL TRIALS
Transferring knowledge
Science depends on networks: to be able to efficiently develop new drug products, researchers rely on information
from their colleagues working in related therapeutic areas. Bayer HealthCare is therefore now providing access to
anonymized patient data from its clinical trials on an online platform in support of a new transparency initiative.
Photo: Getty images (1)
Valuable findings: the data that doctors derive from clinical trials have to be carefully
evaluated. The new online platform now allows scientists access to anonymized source
data of clinical trials.
Clinical trials are an important stage on
the road to a new drug product: they can
provide scientific evidence that the new
treatment is effective and safe for patients to use in a specific indication. But
the massive pile of data collected during
a clinical study may also contain valuable
information for other scientists working
in related therapeutic areas. Bayer HealthCare is now supporting an exchange of
such information by providing access to
anonymized patient data on the online
platform www.clinicalstudydatarequest.
com, in compliance with the terms of an
agreement of the European Federation
of Pharmaceutical Industries and Associations EFPIA and its counterpart in
the United States PhRMA. “We hope that
this transparency initiative will generate
knowledge that will facilitate innovative
therapeutic approaches or allow reevaluation of existing treatments,” explains
Dr. Johann Brüning, Head of Clinical Trial
Transparency at Bayer HealthCare.
Expert committee decides
which data are released
Following the completion of every clinical
study, physicians and scientists evaluate
the compiled data thoroughly to determine the efficacy and safety of the drug
product for future patients. Summaries
of these findings are available in public
databases on Bayer’s homepage and on
the website of the U.S. health authorities.
Both websites also contain information
about ongoing and planned clinical trials.
The database now launched is the
product of an initiative by several pharmaceutical companies in 2014. For the
first time, Bayer scientists are sharing
more than just their clinical trial results:
“We will also make the anonymized
source data of our assessments available,
for our drug products that have been
granted regulatory approval in Europe
and the United States from 2014 onwards,” explains Brüning. The trial protocols and detailed result reports will also
be provided.
Anybody interested in the data can
register on the website to view a list of
available studies and propose research
projects for specific studies. An independent expert committee of international scientists decides which data may
be made accessible to third parties and
which research projects will be supported with these data. “We have to make
sure that the patient data are handled
responsibly,” explains Brüning. It’s an
effort that is extremely worthwhile from
the perspective of the companies that
are involved to date - and one that will
help to make new treatments available to
patients worldwide more efficiently and
quickly.
www.research.bayer.com/clinicaltrials
More information on this topic
Bayer research 26 July 2014
31
MOLECULAR SPECTROSCOPY – OTTO BAYER AWARD GOES TO PROFESSOR FRÉDÉRIC MERKT
Camouflaged ions
Every molecule has its own spectrum – its specific fingerprint – which researchers use to try and ascertain the properties of particles. Professor Frédéric Merkt of ETH Zurich University in Switzerland has achieved a breakthrough – the
laser light sources, spectroscopic instruments and methods he has developed enable key ions to be characterized for
the first time. This achievement has now won him the Otto Bayer Award.
Particle experts: Professor Frédéric Merkt (left) and his team, including Pitt Allmendinger, have carried out spectroscopic research into ions.
32
Bayer research 26 July 2014
Otto Bayer Award MATERIALS
Supporting cutting-edge research
The Otto Bayer Award is presented by the Bayer Science & Education
Foundation. It honors scientists who have made pioneering research contributions in innovative fields of chemistry and biochemistry.
The primary objectives of the foundation are the recognition of outstanding
research achievements, the promotion of talented researchers and support
for significant school projects of a scientific nature.
Seeing through the light spectrum – chemists including Heiner
Sassmannshausen have themselves developed some of the laser light
sources and equipment they work with in ETH Zurich’s laser laboratory.
The world is being measured in ever
greater detail, from one size extreme to
the other. Physical chemistry experts are
also involved in this task: they characterize atoms and molecules and model complex chemical reactions such as
combustion in power plants and engines
and the greenhouse effect in the atmosphere. In addition to providing more
accurate predictions of changes to the
climate, this also optimizes production
processes in the chemical and automotive
industries. The knowledge chain starts
with understanding individual molecules
and elementary processes. But some of
these present puzzles for researchers. One
type of molecule has always proved scientifically problematic – the electrically
charged particles known as ions.
Photos: Peter Ginter/Bayer AG (2)
The trick is to skillfully
­camouflage ions
The problem is their charge. Ions repel each other in the same way as two
identical poles of a magnet. “This interferes with measurements, making them
insensitive and inaccurate,” says Professor Frédéric Merkt, a chemist at ETH
Zurich University in Switzerland. He and
his team have succeeded in defining
the properties of key ions such as the
methane cation CH4+, the ozone cation
O3+ and the hydrogen molecular ion H2+.
They have done so by transferring the
molecules to a Rydberg state. “This cam-
ouflages the ions to a certain extent and
removes the undesirable charge,” continues Merkt. The 47-year-old has received
the Otto Bayer Award in recognition of
his work.
As Merkt explains, anyone who is
looking to characterize a molecule needs
to know how it rotates, how the atoms
oscillate around their center of gravity
and how the electrons move around the
nucleus. This enables the exact chemical
and physical properties to be defined. In
molecular spectroscopy, light – electromagnetic radiation – excites the molecules and induces further photochemical
and photophysical processes in them.
This creates a specific spectrum for each
molecule.
“It also proves molecules are actually
present,” says Merkt. This is of interest to
scientists including astrophysicists and
atmospheric physicists, who use molecular spectra to investigate how the
atmosphere changes. They can benefit
from Merkt’s work, because ions are also
generated in the upper layers of the gaseous geosphere. The solar radiation there
contains so much energy that a large
number of molecules are ionized. A negatively charged electron splits off from
the molecule, leaving behind a positively
charged particle – a cation.
The spectra of many key cations
were previously unknown, but Merkt’s
team tracked down the reluctant molecules. “We transfer uncharged molecules
to a hybrid state between charged and
uncharged,” he explains. To do so, the
researchers excite one of the outer electrons with vacuum ultraviolet light that
causes thousand-fold swelling of the
molecules. The outermost electron in
these giant molecules adopts a very high
orbit. Merkt compares it with a satellite
that is just still held by the Earth’s gravity. “A little more energy and the electron
would split off, leaving behind a cation,”
he says. This highly excited state is also
called the Rydberg state.
Rydberg state enables ions
to be measured
The molecules are uncharged but resemble a cation. “This means they behave
almost like ions but don’t repel each
other,” explains Merkt. The findings of
spectroscopic research on Rydberg states
can therefore be transferred to ions. “The
spectra also enable detailed research into
the interactions between ion and electron
and the elementary process of photoionization,” he says. Consequently, there’s
still a long way to go in the field of molecular measurement.
www.research.bayer.com/spectroscopy
provides further information on this topic
Bayer research 26 July 2014
33
BAYER FOUNDATIONS Current highlights
AWARD-WINNING JUNIOR RESEARCHER: PLANT SPECIALIST DR. STEVEN SPOEL
Decoding the immune system
The Bayer Science & Education Foundation promotes top research and junior talents. Molecular biologist Dr. Steven
Spoel won the 2013 Early Excellence in Science Award for his research into the genetic regulation of the plant immune
system. His work on plants may even be transferable to cancer research.
Understanding plants – healing people: biologist Dr. Steven Spoel studies how the immune system functions on a cellular level and how it can
be influenced.
Many important discoveries in the life sciences are first made
on plants and later applied to humans, which may also be
the case with the work of Dr. Steven Spoel. The 34-year-old
Dutchman is currently a Royal Society University Research
Fellow at the University of Edinburgh’s Institute of Molecular
Plant Sciences. Spoel has specialized in the immune system
of plants or, more accurately, one puzzle piece of it, because
the plant defense system is a complex structure of regulator
genes. “I’m interested in how plant cells detect and respond
to environmental changes,” Spoel says. His work centers on
plant responses to pathogen infestation. Whether a plant grows
and survives depends on numerous factors. In addition to nat-
34
Bayer research 26 July 2014
ural enemies, such as insects and bacteria, growth is influenced by the nutrient and water supply, and by high and low
temperatures.
Researchers are rapidly learning more about the interplay between the environment and the plant immune system,
and in the process expanding their options for arming plants
against adverse conditions. “This is a very critical goal if we
want to feed the growing global population. Furthermore, the
importance of utilizing plants as a source of energy or as drug
producers is likewise on the rise,” Spoel explains. In addition
to making plants more resistant and crop yields more stable,
Spoel hopes his research will have another effect: “On a c­ ellular
BAYER FOUNDATIONS Current highlights
Early Excellence in Science Award
First established in 2009, the international Bayer Early Excellence in Science Award recognizes talented young scientists in the
early stages of their academic careers. An independent expert jury selects three prizewinners in the categories Biology, Chemistry
and Materials. Criteria include the originality of the research, as well as the quality and significance of the results. The awards
are worth EUR 10,000 each. The other awards in 2013 went to the chemist Dr. Abigail Doyle of Princeton University and Dr. Javier
Fernandez of Harvard University in Boston. Doyle developed a method for the low-impact and efficient incorporation of fluorine
in organic molecules. In the future, this will make it possible to synthesize substances with unique, previously unknown properties.
Fernandez discovered a new material called “shrilk.” It displays strength and toughness similar to that of aluminum, but weighs
only half as much, is biodegradable, suitable for complex molding processes and can be produced at low cost. The material has
potential for use in numerous applications, including packaging and medicine.
l­evel, there are several similarities between the plant and human immune systems. Our research may also uncover possibilities for new cancer treatments.” In recognition of his work,
Spoel won the 2013 Early Excellence in Science Award, funded
by the Bayer Science & Education Foundation. The puzzle piece
he concentrates on in his research is salicylic acid. This starting component for acetylsalicylic acid, the active ingredient in
Aspirin™, is part of a plant’s system of defense against harmful
organisms.
Veterinarian in Namibia
The 25-year-old veterinarian Marion Leiberich is a fan of Africa.
While in college, she used her Carl Duisberg scholarship from the
Bayer Foundation to fund an internship at the Windhoek Veterinary
Clinic in Namibia.
Photos: Bayer AG (1), private (2), Dirk Hansen/Bayer AG (1), Markus Müller-Saran (1)
Help against pathogens: salicylic acid induces
gene expression and activates the immune system
“We know that the plant immune system can switch on specific
gene groups to fight pathogens,” Spoel explains. Salicylic acid
helps it correctly transcribe information in the DNA and switch
on the genes required for defense. “Many of these molecular
mechanisms in which salicylic acid alters genes exist in the cells
of both man and animals,” he continues. Errors in this sensitive
network have an impact on the metabolism of the entire organism, potentially leading to faulty immune system reactions and
the development of disease. “We need to understand in greater
detail what effect salicylic acid and other factors have on the
finely balanced regulation system, and how we can influence
these effects,” Spoel says.
Spoel became fascinated with the immune system activator
while working on his dissertation at Duke University in North
Carolina, USA. He had previously completed his undergraduate
studies at Utrecht University in the Netherlands. Spoel knew at
a young age that he wanted to dedicate his career to plants. His
parents gave him and his siblings a corner of the yard to plant
seeds and to water, fertilize and observe the growing plants.
“Within a short time, I had taken over my siblings’ plots,” Spoel
remembers. To compensate for all the hard work, the biologist
likes to practice judo, a sport he has been involved in since
he was five. Spoel also participates every year in the Glasgow
half marathon. This stamina and perseverance could very well
reward him with a promising career – and new discoveries in
cancer research as well.
Practical experience: Marion Leiberich in the operating room
What draws you time and time again to Africa?
Ever since we took a family vacation there, I have been fascinated
by the landscape and animal world of Africa. Between high school
graduation and college, I spent nine months working for a chimpanzee protection project, observing lions for a research project
and volunteering for whale and dolphin research. I also spent all my
semester breaks in Africa.
How did you benefit from the internship?
I examined and x-rayed animals, and assisted with ultrasound examinations. I was even allowed to operate. If I can add to this experience by working with wild animals, then hopefully I can be accepted
into the Wild Animal Health program in London.
Bayer research 26 July 2014
35
BAYER FOUNDATIONS Current highlights
Chemist in training at
the Bayer laboratory
After earning his master’s degree in chemistry, Sebastian Keess spent
five months in Chemical Development at Bayer HealthCare. We spoke
with the 25-year-old Bayer “Deutschland” scholarship-winner about
his experience.
What fascinates you about chemistry?
First and foremost the possibility of transforming molecules into
substances with entirely different properties, and thereby helping
to solve some of the greatest challenges of our age.
What were your responsibilities working as an intern at Bayer
HealthCare?
I worked for Global Drug Discovery on the chemical and pharmaceutical development of new drugs. My main job was to study efficient chemical synthesis processes for potential active substances
and to optimize their production sequences.
How did you benefit from the scholarship?
I used the money at the university primarily to buy chemicals. The
experience I gained from application-oriented research at Bayer
Industrial experience: Bayer scholarship-winner Sebastian Keess
(center) talks with Thimo V. Schmitt-Lord (left) and laboratory head
Dr. Daniel Götz (right) about his work in Global Drug Discovery at
Bayer HealthCare in Wuppertal.
opened up entirely new prospects for me: my experiences in the lab
will definitely help me make decisions about my future career.
But first I would like to earn my PhD the classical way, at the Berlin
University of Technology, and then go abroad for a while. After that
it will be time to decide between a career in industry or academia.
Commitment to Nepal
Since receiving her bachelor’s degree,
physical therapist Alexandra Hummel has been living for her career.
With the help of a Hermann Strenger
scholarship, she financed an internship at a clinic in Nepal. “Physical
therapy is virtually non-existent in
Nepal,” she relates. She was attracted to Nepal by “the high mountains
and because you encounter medical
cases there that you normally do not
see in Europe.” After volunteering
and going for her master’s degree
in physical therapy, Hummel says
she would like to work in clinical
research: “Using efficacy studies,
we can determine which treatments
really help.” Health insurance companies frequently request this kind of
scientific evidence.
36
Bayer research 26 July 2014
Volunteer work: at the Nepal Clinic in
­ hitwan National Park, Alexandra Hummel
C
applies kinesio tape to a Nepalese patient
with arthritis of the knee.
How to apply
The Bayer Science & Education Foundation’s
tailored scholarship programs support young
talents in Germany and abroad, helping them
to reach special academic and career goals.
All young people from Germany who are planning a study or vocational training project
abroad, or foreigners planning similar projects
in Germany, are invited to apply. The foundation also offers “Deutschland” scholarships
for college students. Applicants should have
two things above all: pioneering spirit and a
unique project idea which the Bayer Foundation can help to implement as a partner. For
more information on the application process,
call +49 (0)214/304 11 11, visit the internet
site at www.bayer-foundations.com or send an
e-mail to: scholarships@bayer-stiftungen.de
BAYER FOUNDATIONS Current highlights
INNOVATIONS AT THE INTERFACE BETWEEN BUSINESS, SCIENCE AND HEALTH
Doctor’s office interpreters
The Bayer Cares Foundation supports social innovation, for example at the interface between patients and the health
care sector. A student initiative called “What have I got?” won the Audience Prize in the 2014 Aspirin Social Award and
placed ­second overall. It is a free service that translates medical terms into comprehensible, everyday language.
The results are sobering: according to studies, most patients
have forgotten 80 percent of what their doctor said by the
time they leave the office. Since January 2011, a group of
­dedicated young doctors headed by Anja and Johannes ­Bittner
and Ansgar Jonietz has been working to resolve this situation: At their online portal www.washabich.de, patients can
enter their medical results in text form, upload a file or send
a fax. A few days later they receive a text that a layperson
can better understand – protected by password, discrete and
free of charge. “What have I got?” is funded mainly by donations, sponsors and financial awards like the Aspirin Social
Award’s Audience Prize. “The prize money helps us to translate medical terminology into standard German,” explains
Anja Bittner.
A patient with shoulder pain, for example, who undergoes
an MRI and gets a diagnosis that reads “cortical depression of
the humeral head,” learns that the hard, outer layer of bone (referred to medically as the cortical bone) on the top of his upper
arm bone (the head of the humerus) – is indented. Furthermore,
he receives a clear explanation of what an MRI is capable of
visualizing, how the shoulder joint is structured and a diagram
of aspects relevant to his case. “A complete translation takes
about five hours,” Bittner says. A thousand physicians are now
involved in the program, of whom about 200 actively participate
in the translation work. All of them were first trained in how to
communicate more effectively with the lay population, something that benefits their everyday work with their own patients
as well.
But “What have I got?” is not the only initiative that aims to
benefit patients through new social programs. First place in the
Aspirin Social Award went to the mobile telephone app “Explain
TB.” This free service from the Borstel Research Center teaches
patients and their families about their disease. Tuberculosis is
a life-threatening disease of the poor that infects half a million people every year in Europe alone, including many children
and the illiterate. Half of all TB patients in Germany come from
countries outside Europe. The “Discovering Hands” initiative is
dedicated to another disease: blind and visually impaired people are taught how to physically detect breast cancer for the
purpose of early diagnosis and trained to be physical examiners. This innovative concept aims to help break down prejudices
against people with physical disabilities and promote respect for
their superior sense of touch.
Patient translators: Junior physicians Anja Bittner, Ansgar Jonietz and Johannes
Bittner (from left) translate medical diagnoses into more understandable language
for laypeople. About a thousand physicians already participate in the online portal
at www.washabich.de.
Employee volunteering
The Bayer Cares Foundation is also active in human resources development: “Three Bayer employees will each fly to different continents for three
months in 2014 to participate in social projects and look for new answers
to unsolved problems,” says Thimo Valentin Schmitt-Lord, Chairman of the
Bayer Foundations. Their destinations are in developing countries where
there is a demand for health education and medical care. For example,
Bayer is launching a project in the Philippines to rebuild the country’s destroyed health care infrastructure, and a Bayer Business Consulting employee will be there to provide assistance locally.
www.bayer-foundations.com
Visit this site to apply or to obtain more information.
Bayer research 26 July 2014
37
HOSPITAL HYGIENE: SPECIAL MATERIALS HELP IN THE FIGHT AGAINST INFECTIONS
Germs don’t stand a chance
Standards of hygiene in hospitals are high: patients who are weak or have recently undergone surgery are easy prey for
bacteria and germs. It is not just a matter of doctors and nurses disinfecting their hands and their clothing; in addition,
rooms need to be regularly cleaned. Materials experts at Bayer MaterialScience have now developed an extremely robust
wall coating that makes it easier to combat harmful germs – and saves the health service a lot of money.
The danger usually lies dormant, hidden away: in hospitals, germs such as
resistant bacteria or normally harmless
intestinal bacteria can spread – and put
patients’ health at risk. For of all places, it is here, where hygiene standards
are at their highest, that stubborn and
harmful microorganisms can grow –
toughened in their daily fight for survival against antibiotics and cleaning
agents. According to a study by the European Centre for Disease Prevention
and Control (ECDC), 3.2 million people
each year in Europe acquire an infection
while in hospital. Approximately 80,000
patients per day require treatment for
hospital acquired infections (HAI) that
they have contracted while undergoing therapy. For weakened patients, the
consequences may be life-threatening:
pneumonia, urinary tract infections
and wound infections or even blood
poisoning. Worst affected are patients
in intensive care.
The unwanted germs can gain a
hold anywhere. Thorough hygiene
measures are therefore the rule in every
80
percent
38
hospital: hands, the patient’s personal
possessions, laundry and refuse have to
be comprehensively disinfected. There
are also strict rules dictating how the
cleaning staff need to clean the floors
and walls, from operating theaters to
corridors. To remove particularly stubborn bacteria as well, this usually involves ­using very strong disinfectants
– but there is a drawback: “The aggressive cleaning agents generally fiercely
attack the walls in patient rooms and
in the corridors,” explains Scott Grace,
Head of Application Development at
Bayer MaterialScience. As a result, colors change and sur­faces become porous.
“The colors are durable,
“Not only does this quickly look shabby,
nearly odorless on appli- it is sometimes a­ lso counterproductive,
as it is then even easier for bacteria to
cation and low-gloss.
gain a hold than on smooth surfaces,”
Until now, no paints com- says Grace. And it is costly: patient
bining all three properties rooms or waiting areas consequently
have to be repainted up to four times
have been available.”
per year. “In the USA, this costs around
US$ 3,000 per room. On top of that, the
Steven Reinstadtler,
Bayer MaterialScience
rooms being painted are obviously out
of action for a while which means lost
revenue for the hospital,” adds Steven
Reinstadtler, Construction Marketing
Manager Coatings.
The materials experts working with
Grace have therefore developed a new technology for wall paints.
This HD (high durability) polyurethane coating has markedly betHospitals can reduce their
ter resistance to scrubbing with disinfection agents. “Coatings
painting and cleaning costs by
with the Bayer technology are up to four times more durable
up to 80 percent on average
than conventional wall paints,” says Grace. And that saves
by using robust wall coatings.
­money: “Durable paints reduce costs for robust walls in a hospital by up to 80 percent on average. This makes a huge difference
Source: Bayer MaterialScience, market research
financially,” explains the Bayer expert.
Bayer research 26 July 2014
Hospital hygiene MATERIALS
Invisible hazard: dangerous, resistant bacteria can ­
develop in hospitals. Every year in Europe, 3.2 million
­people acquire an infection while in hospital.
Photos: private/Bayer AG (1), Oliver Meckes & Nicole Ottawa/eye of science/Agentur Focus (1), Getty images (1)
The secret of the durability of the Bayer paint lies in its special composition: it consists of two components that chemically
crosslink. The matrix of the new HD coating consists of polyurethane. It is very resistant to abrasion and does not dissolve even
on contact with caustic chemical cleaning agents. The matrix is
formed by reacting a water-based hydroxyl polyacrylic dispersion with a water-soluble isocyanate molecule with very high
reactivity, crosslinking the components very densely with one
another. These many close bonds form an extremely tough and
durable surface. “Water and chemicals are virtually unable to
penetrate and damage the coating. This means that there are
fewer indentations or cracks in which germs or dirt can collect,”
explains Grace.
Technology can be modified for
different applications
Other robust wall coatings are already available but these have
two distinct disadvantages: conventional paints are usually
based on strongly smelling solvents, and most robust wall coatings are high-gloss. Neither is a problem outdoors, such as for
painting bridges or pipes. Inside buildings, however, odors and
high-gloss effects are unwelcome. And this is precisely where the
Bayer technology comes into play: “The colors are durable, nearly odorless on application and low-gloss. Until now, no paints
combining all three properties have been available,” summarizes
Reinstadtler. With this paint, the Bayer materials experts are responding very specifically to the wishes of architects, painting
firms and hospital managers: “We got together with everyone
involved in the value added chain – such as facility owners,
specialists from painting firms and paint manufacturers – and,
as a result, developed a high-quality product that meets all requirements and, above all, takes into account the cost factor,”
explains Grace.
The Bayer experts had originally developed their HD technology for scratch-resistant and robust floor coatings. “But we
then took the concept further and adapted it, for example, to
exterior paints for protecting against unwanted graffiti,” continues Grace. The painted surfaces are so smooth that graffiti
can simply be washed off with water. “We are firm believers in
this technology, which is why we have also optimized it for use
in hospitals,” adds Grace.
The first walls painted with the Bayer technology are already
dry in the USA – and it has also been used, for example, in the
concession areas and restrooms at the stadium of the Los Angeles Dodgers baseball team. The potential of the wall paints
is far from being fully exhausted, however: experts have used
the Bayer technology to develop a new transparent coating that
converts a wall into a giant whiteboard. “This offers whole new
design options for schools, for example,” says Grace. The Bayer
experts are also constantly seeking new applications for their
technology. As Grace explains, “With antibacterial substances as
additives, there is still further potential in the hygiene sector.”
Bayer’s experts are not running out of ideas just yet – and not
only in the fight against hospital germs.
www.research.bayer.com/hospital-hygiene
More information on this topic
Bayer research 26 July 2014
39
SYNERGIES: INTERDISCIPLINARY BAYER TEAM CONDUCTS RESEARCH INTO ION CHANNELS
Molecular gatekeepers
Whether a movement of the muscles or a beat of the heart: the cells in the bodies of humans
and animals communicate with each other by means of electrical and chemical signals. The
most important elements in the information cascade are ion channels. These protein ­molecules
are therefore potential targets for new drug products, but also for insecticides in crop p­ rotection
and parasiticides in veterinary medicine. Medical, veterinary and crop protection specialists at
Bayer are now working together in interdisciplinary teams to find new active ingredients.
Ion channels are important
targets for human drug
products, but many antipara-
sitic agents and crop protection
products likewise influence
these cellular gateways to kill
ticks, aphids and fleas.
The cell membrane is
impermeable to all ions.
They can only pass through
via ion channels.
Ion channels are specific:
each channel only allows
certain kinds of ion to pass.
40
Bayer research 26 July 2014
Ion channels SPECIAL FEATURE
The language of
the cells
Ion channels are important for
conducting stimuli between
nerve cells, for example. Excitation of a cell releases signal
molecules.
The human body comprises some 75 trillion cells,
all of which have to cooperate so that life can
function. The cells therefore communicate with
each other. The basic principle involves excitation. Ion channels often play an important role in
this process. They open and close as the result of
chemical and electrical signals. When open, they
form a gate through which electrically charged
particles (ions) can pass into or out of the cell, thus
regulating the electrical charge distribution in the
membrane and conducting the originally received
signal to other cells. This fundamental function
makes ion channels an important target for many
drug products, for example medicines to treat
­cardiac arrhythmia, hypertension and diabetes.
These signal molecules
bind to specific ion channels
in neighboring cells, causing
the channels to open.
Ions can pass through a
channel at rates of up
to 100 million ions per
second.
The influx of ions produces an
electrical impulse that the cell
passes on.
Bayer research 26 July 2014
41
SPECIAL FEATURE Ion channels
Everything has its place, especially in human, animal or plant
biological cells. Only selected substances get inside the building
blocks of life, thanks partly to ion channels. They control the cell
membrane’s entrances and exits and give only special electrically
charged ions free access to the cell. And the ions have to hurry,
because the channels close again after just a few milliseconds.
Many cells have up to a million such gatekeepers, each of which
is responsible for one specific kind of ion. This enables a targeted exchange of sodium, potassium, calcium and chloride ions
in the nerves and tissues and makes possible the conduction
of signals from one cell to the next. “Ion channels regulate the
heart rhythm in humans and animals, for example, or convert
stimuli like light, cold or heat into nerve signals,” explains Dr.
Thomas Müller from Bayer HealthCare’s Global Drug Discovery
department. Errors in this process can trigger severe disorders
such as atrial fibrillation. Ion channels are therefore an extremely
interesting topic in pharmaceutical research. “We’re looking for
new pharmacological targets in both cardiology and women’s
healthcare,” says Müller.
The patch clamp
­technique
The gold standard for studying ion channels is the patch
clamp technique. This method involves sucking a membrane
surface area or “patch“ from a cell onto an ultra-thin glass
pipette. This produces a tight seal between the cell and the
pipette, which is filled with electrically conductive fluid. The
current of a single ion channel can then be measured. The
method was developed by Bert Sakmann and Erwin Neher,
who received the Nobel Prize in Physiology or Medicine for
this work in 1991.
Today, scientists use this technique to develop substances
that act on ion channels. It allows them to demonstrate in
cell cultures whether the active ingredient influences the
channel in the desired manner - in other words, opens, closes
or blocks it.
However, in the early stages of drug development in particular, there are still numerous potential active ingredient
candidates - too many to test them by hand. Scientists could
only investigate about 100 compounds per month that way.
Bayer has therefore invested in a state-of-the-art patch
clamp robot, which is capable of testing some 20,000 active
substances in cell cultures fully automatically every month.
nervous system goes haywire. This mechanism of action helps
imidacloprid not only protect apple orchards against sucking
aphids but also dogs and cats against annoying fleas.
Leveraging synergies: research in all areas
­overlaps during the early stages
Research collaborations: Dr. Thomas Müller, Dr. Dirk Heimbach and Dr. Horst
­Antonicek (left to right) are collaborating intensively in the development of new
compounds for human, animal and plant health.
Scientists at Bayer CropScience are also conducting intensive
research into ion channels, because the signal conduction process in crop pests such as aphids and spider mites or in parasites
of companion animals likewise relies on the molecular gatekeepers. “There are many insects that can be harmful and are
therefore unwanted in agriculture and animal health,” says Dr.
Ulrich Ebbinghaus-Kintscher, Head of Neurophysiology at Bayer
CropScience. Ion channels have therefore long been a popular
target for active ingredients such as imidacloprid, for example.
This Bayer active substance combats sucking aphids and fleas
on companion animals by binding to a specific ion channel, thus
keeping the channel open. As a consequence, the insect’s entire
42
Bayer research 26 July 2014
Even though it may appear that there is a huge divide between
applications in human medicine and those in veterinary medicine
and crop protection, a look at the molecular details reveals numerous common features. “In the early stages in particular, there
is a lot of overlap in the research in crop protection, veterinary
medicine and human medicine,” confirms Ebbinghaus-Kintscher.
Bayer is focusing on these synergies: the company is networking
its Life Science subgroups closely together as part of an initiative called the Nimbus project, and promoting the exchange of
information with the objective of finding new approaches for
new active ingredients.
Bayer scientists are also leveraging these synergies in the
search for active substances that target ion channels. Their work
is always focused on one specific ion channel: crop protection
researchers like Ebbinghaus-Kintscher, for example, are concentrating their attention on an ion channel in aphids. Modulating
this channel kills the insect pest. “First of all, we use cell cultures
Born communicators: nerve cells, or neurons, are perfectly adapted to passing on information, as their appearance clearly shows: each cell body has
numerous structures branching off it that make contact to other neurons. The photo above shows a neuron under 3,000-fold magnification.
to test whether the new substances have the desired effect,” explains Dr. Horst Antonicek, Head of Target Biology at Bayer CropScience. To this end, millions of molecules are tested by means of
automated processes night and day. What’s more, the crop protection scientists use not only their own substance libraries but
also have access to the active ingredients from their colleagues
at Bayer HealthCare. “Together, we can choose from more than 5
million compounds. This variety of chemicals increases the chance
of actually finding a new lead structure,” explains Antonicek.
Photos: Dirk Hansen/Bayer AG (1), Manfred Kage /Okapia (1)
Thanks to new technology, scientists can test
more active ingredients in a shorter time
Frequently, however, thousands of molecules are still of interest after the first tests. “We then submit these compounds to
electrophysiological testing using the patch clamp procedure,”
says Ebbinghaus-Kintscher. This method involves measuring the
tiny electrical flow of ions through the channel using an extremely thin glass pipette, with and without an active substance.
“They’re complex tests. If we always did them manually, it would
take years,” says Antonicek. That’s why there is now a state-ofthe-art patch clamp robot at Bayer’s Monheim site, which can
manage 20,000 substances per month. “This is a quantum leap.
Previously we could only test up to 100 substances in that time,”
says Antonicek.
Of course, not just Bayer CropScience benefits from this; all research departments can use the new ion channel platform. It also
opens up new opportunities at Animal Health. “In the past, we
were only able to take over established active substances from
crop protection research,” explains Dr. Dirk Heimbach, Head of
Chemistry at the Animal Health department of Bayer HealthCare’s Global Drug Discovery unit. “Now we have completely new
opportunities for research into areas that are only of interest for
animal health, such as tick- or worm-specific ion channels.” And
the results of these studies can, in turn, benefit the colleagues
at Bayer CropScience.
But while there is extremely close cooperation at the start
of the search for active substances, the scientists’ roads diverge
again once electrophysiological screening has been completed
and the first prototypes have been selected. The jointly identified
active ingredient classes are then tested with regard to their specific action on humans, animals and plants and then selectively
optimized. Nonetheless, the initial stages of research into the
molecular gatekeepers are very similar, and the joint efforts such
as the screening platform enable better and faster development
of new active ingredients, for human and veterinary medicine as
well as for crop protection.
www.research.bayer.com/ion-channels
More information on this subject
Bayer research 26 July 2014
43
PROFESSOR JOHANNES-PETER STASCH ESTABLISHED AN ENTIRELY NEW FIELD OF RESEARCH AT BAYER
A pioneer in the service
of patients
Chemist and pharmacologist Johannes-Peter Stasch has dedicated his scientific career at Bayer HealthCare to helping
patients who suffer from conditions like pulmonary hypertension, for which no drug therapies were available for many
years. His work has met with success: today “his” first drug is available on the market and several hundred researchers
are working on the biochemical signaling cascade that first fascinated this Bayer scientist all those years ago.
The untiring researcher: Professor Johannes-Peter Stasch is not one to rest on his laurels and is continuing to work on new active ingredients.
44
Bayer research 26 July 2014
Professor Johannes-Peter Stasch PORTRAIT
Photos: Sabine Bungert/Bayer AG (2), Jörg Klaus/Bayer AG (1), Peter Ginter/Bayer AG (1), Michael Rennertz/Bayer AG (1), private (2), Markus Scholz for Leopoldina (1)
Professor Johannes-Peter Stasch smiles as he recalls that “as a
child, I was always asking Why not?” Even now, challenge clearly
only motivates him even more. “Someone saying, ‘That’s impossible!’ always triggers a reaction in me,” he admits. This attitude
has been good news for many patients, in particular for people
with cardio-pulmonary diseases such as pulmonary hypertension, or chronic heart failure. “My research is for people suffering
from severe illnesses for which no drug treatments previously
existed,” Stasch explains. It’s what motivates him, and a cause he
champions among his colleagues in the scientific world outside
the Bayer organization as well. Stasch is not a medical doctor;
he is a chemist and pharmacologist at Bayer HealthCare’s Global
Drug Discovery department. He develops new pharmaceutical
active substances, and only rarely comes into direct contact with
patients. Nevertheless, the 60-year-old always has the people
he wants to help in mind. His passion for his subject knows no
boundaries; he is renowned for working nights and weekends
on their behalf. Stasch has more than 150 scientific articles on
his publications list, including contributions to the prestigious
research journal Nature. This industry researcher, who began his
career at Bayer HealthCare 30 years ago, has earned the respect
of the academic world for his achievements.
A scientist with innovative ideas and infectious
enthusiasm for new medicines
In 2010 he was named Honorary Professor of Drug Research by
Halle-Wittenberg University. In 2013 he received one of the greatest honors bestowed on scientists in Germany by being elected a
member of Leopoldina, the German National Academy of Sciences.
Stasch is not the kind of researcher who stays holed up in his
laboratory behind a mountain of textbooks. He has a well-de-
Bayer scientists in debate: Dr. Dieter Neuser, Dr. Stephan Vettel and
Professor Johannes-Peter Stasch (photo above right, left to right)
discuss a model of the lung. Stasch spends lots of time working in his
laboratory in Wuppertal with colleagues like Yvonne Keim, Andreas
Hucke and Christina Jochem (photo above left, left to right), but also
enjoys visiting Berlin (top photo).
served reputation as a lively and motivating speaker. “It’s important to sell your results, to go public and get others excited
about them,” he says. Apart from his prolific writing, his inquisitive mind has led to more than 200 patent applications.
When asked for particular memories, Stasch is quick to bring
to mind one patient: a young woman suffering from pulmonary hypertension. In this severe, progressive disease, the walls
of the pulmonary arteries thicken, becoming stiff and increasingly inflexible. The supply of oxygen to the bloodstream is
decreased as a result, leading to a risk of heart failure. “This
woman could hardly lead a normal life,” Stasch relates. “Even
Bayer research 26 July 2014
45
The substance that dilates blood vessels
One of the active substances at Bayer is member of a class of vasodilators known as soluble guanylate cyclase (sGC) stimulators. Soluble
­guanylate cyclase is an enzyme that plays an important part in the
cardio­vascular system. It is activated by the nitrogen monoxide produced by the human body. Following activation, it stimulates production of a cellular messenger substance known as cyclic guanosine
monophosphate or cGMP. This molecule in turn dilates the blood vessels. In many cardiovascular diseases, however, this signaling cascade
does not function properly. In some cases, too little nitrogen monoxide
is available, the sGC enzyme does not react adequately, and not enough
cGMP is produced. The blood vessels constrict in response, such as in
the case of pulmonary hypertension. This is where the sGC stimulator
intervenes: it stimulates the enzyme to increase cGMP production even
independently of the nitrogen monoxide (NO) messenger substance. See
also “Acquisition” on page 5.
the slightest exertion caused her heart to pound wildly. She was
short of breath and constantly tired.” But then she took part
in a clinical study. The object of the study was an active substance in the class of sGC stimulators. During her participation
in the study her health status improved. “She could climb stairs
again, go to work and do the things she wanted to do. Her
whole family benefited,” says Stasch, with no attempt to hide
how moving that moment must have been for him. As the full
story of sGC modulation unfolded, through the tireless work
of Bayer researchers, and the particular benefits materialized
for patients with pulmonary hypertension, it became clear to
Stasch: “Our work has paid off, and the active substance has
a very good chance of being approved as a drug for treating
this disease.”
Elucidating, influencing and repairing the
­signaling cascades inside cells
It was an overwhelming moment: because the highpoint of
any pharmacologist’s career is the day a new active substance
discovered by him is approved by the regulatory authorities.
Only few ever get to enjoy such an achievement. Johannes-­
Peter Stasch puts it this way: “Discovering and developing a
new pathway is rare but also very exciting. Very correctly, the
review of a compound with a new mechanism of action is a
painstaking exercise.” He is therefore all the more pleased that
he succeeded in decoding a signaling pathway – and with it a
small part of the complex machinery inside the cell – and was
even able to influence it.
It was a long and arduous journey that began in 1994. At
Bayer’s Research Center in Wuppertal, Professor Stasch and his
colleagues had just discovered and synthesized the first sGC
stimulators. These active substances were shown to trigger a
46
Bayer research 26 July 2014
Expert in sGC stimulators: Professor Johannes-Peter Stasch
­investigated the signal molecules that dilate blood vessels.
complicated signaling cascade inside cells that in the end causes
the blood vessels to dilate. As a result, Stasch and his team felt
they could be useful for a number of diseases, not only cardio­
vascular but also for kidney and liver disorders, and various
forms of dementia, because all these conditions are associated
with similar biochemical mechanisms.
In dialog with outstanding scientists and Nobel
laureates worldwide
Unfortunately, research on sGC stimulators was always threatened by termination, because the substances, though promising,
did not fulfill all requirements. Stasch repeatedly had to negotiate with management, get them interested in the potential of
his work, even to the point of confrontation, “and show as much
perseverance as I could muster.”
From the very beginning, Stasch was committed to close
collaboration with universities and research institutions. “The
partnership between the industrial and academic worlds is
beneficial to both,” says Stasch, describing his view of modern
research. In fact, the idea itself of searching specifically for sGC
stimulators to treat pulmonary hypertension emerged from a
collaboration with researchers at the Universities of Giessen and
Harvard. Today Stasch has established a network of researchers
around the world, including several Nobel prizewinners. “A lot of
personal friendships have developed over the years from working together on the signaling pathway,” Stasch says.
Anyone meeting the dedicated Bayer researcher immediately
realizes that he treats everyone around him with the same candid friendliness. From the colleague who has just returned from
an extended vacation, to the cleaning lady in the laboratory,
he always has a friendly remark or quick joke to share with
everyone. In his free time, he and his wife are involved in com-
Professor Johannes-Peter Stasch PORTRAIT
Milestones in a researcher’s career
Johannes-Peter Stasch (born in 1954) discovered his passion for chemistry at age 10, thanks to a chemistry set. After graduating from
high school in Hameln, Germany, he majored in chemistry at the universities of Hanover and Würzburg. During his subsequent community service, he set up a neurochemical
laboratory at Würzburg University
Hospital. While working on his PhD, he
completed his degree in pharmacy. In
1984 he became a licensed pharmacist
and started his first job, working as
laboratory director at the Institute for
Cardiovascular Research at Bayer AG in
Wuppertal. By 2008 he had risen to the
position of Chief Scientist and become
a member of the Bayer Expert Club,
which advises the Bayer AG Board of
Images from the past: Stasch with his colleagues at the Pharmaceutical Institute in 1990 (photo left, 6th
Management on issues of innovation.
from right) and in 1978 at the Institute for Physical Chemistry at Würzburg University (photo right).
munity and social projects. Although he does not reveal more,
it is apparent that the energy he exudes infects people in these
pursuits just as much as in his scientific work. He even instilled
his enthusiasm for science in his three children: they all grew
up to be engineers.
With his untiring work, Stasch has established an entirely
new field of research virtually from nothing over the last two
decades. “Twenty years ago, it was just four of us sitting here
at this table in my office,” he recalls. Today several hundred
researchers worldwide are investigating sGC stimulators and
the messenger substance cGMP, which has a key function in
the signaling cascade. In 2001 Stasch initiated a congress series
on the subject cGMP, which he now organizes together with
colleagues every two years. Today a lot of them know him only
as “Mr. cGMP.”
Advising high-level
­policymakers
Professor Johannes-Peter Stasch was elected a member of
Leopoldina in 2013. Germany’s National Academy of Sciences is one
of the oldest institutions of its kind worldwide. Leopoldina currently has some 1,500 members, all leading scientists from Germany,
Austria, Switzerland and numerous other countries. The Academy’s
most important task is to advise policymakers: the members of its
interdisciplinary expert groups draw up statements on key socio­
political issues.
Skepticism as a motivator: Stasch counters
­critics with clear ideas and visions
Coworkers at Bayer also are intrigued by Stasch’s achievements. “It is unbelievably impressive to see everything he has
built up over the years,” says for instance Dr. Peter Kolkhof,
project manager in Cardiology Research at Bayer HealthCare in
Wuppertal.
But Stasch himself is not one to rest on his laurels: “We are
only at the very beginning of understanding sGC stimulators,”
he emphasizes, and sees a lot of work ahead. Stasch also wants
to pave the way for another group of active substances, the
sCG activators. These substances stimulate the same signaling
cascade as sGC stimulators, but employ a different mechanism,
activating the enzyme when it is altered by disease. For the sGC
activators there is still a long way to go but thanks to the pioneering work of Stasch, the journey has begun!
Elected to Leopoldina: Professor Johannes-Peter Stasch (8th from left) is a
member of Germany’s National Academy of Sciences.
www.research.bayer.com/stasch
Further information on this topic
Bayer research 26 July 2014
47
TECHNOLOGY Oxygen depolarized cathode
SAVING ENERGY IN CHLORINE PRODUCTION
Efficient electrolysis
Drugs, plastics and electronic components all need chlorine during their manufacture.
­However, the method for producing chlorine – electrolysis of sodium chloride – consumes a
great deal of electric power. Energy efficiency can be improved with the help of the oxygen
depolarized cathode.
“The oxygen depolarized c­ athode
offers significant
ecological and economic benefits.”
3 At the negatively charged electrode –
the oxygen depolarized cathode – hydroxide
ions
are produced from oxygen
and
water molecules . These then combine
with the sodium ions to form caustic soda.
2 The saline solution also contains
sodium ions . These pass through a
membrane separating the two chambers into the right electrolysis cell.
Chlorine
Andreas Bulan
Bayer MaterialScience
Sodium hydroxide solution
Oxygen depolarized
cathode
3
2
1
Volts
30% less
energy
Saline
solution
Water
1 Common salt dissolved in water is
pumped into the left electrolysis cell.
This solution contains chloride
ions , which are oxidized at the
­positively charged electrode to form
chlorine gas .
Chlorine capacity
60 30 Energy-efficient: the introduction of oxygen
not only saves energy, it also reduces CO2 emissions
by 30 percent.
48
Bayer research 26 July 2014
87
68
0 30
1985
2008
2013
Source: CMAI 2013
Photos: Michael Rennertz/Bayer AG (1), private/Bayer AG (1)
Million tons per year
90 -
Masthead
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Responsible for the contents: Dr. Herbert Heitmann
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Editorial team:
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transquer GmbH - wissen + konzepte, Munich
Scientific advisors:
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into actual innovations.
AGRICULTURE
Canola
Pod check: Kevin and Herbert Serfas (photo left, right
to left) assess the canola plants at Ironsprings Farm in
Canada. The ripe, black seeds contain large amounts of
canola oil (photo right).
The stability of the canola pods can be adjusted using reverse genetics. Researchers generate chemical changes (mutations) in the
genotype. The candidates with an IND mutation are backcrossed with the original plant. The canola plants that result from this cross
have stronger seed pods. The seeds stay in the pod and do not fall out when buffeted by the wind.
Undesirable
mutations in
other sections of
the genome
Mutagenesis
As a result of backcrossing and
selection, only the desirable mutation in the IND gene remains.
Desirable
mutation
in the IND
gene
Desirable
mutation in
the IND gene
Ion channels
SPECIAL FEATURE
SYNERGIES: INTERDISCIPLINARY BAYER TEAM CONDUCTS RESEARCH INTO ION CHANNELS
Molecular gatekeepers
Plant
Strong wind
Ion channels are important for
conducting stimuli between
nerve cells, for example. Excitation of a cell releases signal
molecules.
Strong wind
Cross-section
of a canola pod
Cross-section
of a canola pod
targets for human drug
products, but many antiparaDehiscence zone no
Seeds fall
sitic out
agents and crop protection
of the pod
products likewise influence longer present
Seeds
Seeds
Seeds remain
in the pod
these cellular gateways to kill
ticks, aphids and fleas.
28
These signal molecules
bind to specific ion channels
in neighboring cells, causing
the channels to open.
Bayer research 26 July 2014
Ions can pass through a
channel at rates of up
The cell membrane is
impermeable to all ions.
They can only pass through
via ion channels.
to 100 million ions per
second.
Ion channels are specific:
each channel only allows
certain kinds of ion to pass.
40
Bayer research 26 July 2014
Published in July 2014
ISSN 0179-86188
The human body comprises some 75 trillion cells,
all of which have to cooperate so that life can
function. The cells therefore communicate with
each other. The basic principle involves excitation. Ion channels often play an important role in
this process. They open and close as the result of
chemical and electrical signals. When open, they
form a gate through which electrically charged
particles (ions) can pass into or out of the cell, thus
regulating the electrical charge distribution in the
membrane and conducting the originally received
signal to other cells. This fundamental function
makes ion channels an important target for many
drug products, for example medicines to treat
cardiac arrhythmia, hypertension and diabetes.
Ion channels are important
Dehiscence zone
= pre-set breaking
point
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E 2910227606
The language of
the cells
Whether a movement of the muscles or a beat of the heart: the cells in the bodies of humans
and animals communicate with each other by means of electrical and chemical signals. The
most important elements in the information cascade are ion channels. These protein molecules
are therefore potential targets for new drug products, but also for insecticides in crop protection
and parasiticides in veterinary medicine. Medical, veterinary and crop protection specialists at
Bayer are now working together in interdisciplinary teams to find new active ingredients.
As of 2014, research is published twice a year in English and
German. Reprints may be made if the source is mentioned.
Voucher copies are requested.
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name/designation “Bayer HealthCare” or
“BHC” refers to Bayer Pharma AG.
Strategy for shatter-resistant pods
Canola
genome
with active
IND gene
research on the internet: www.research.bayer.com
The influx of ions produces an
electrical impulse that the cell
passes on.
Bayer research 26 July 2014
41
Forward-Looking Statements
This research magazine may contain forward-looking statements based on
current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could
lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given
here. These factors include those discussed in Bayer’s public reports which are
available on the Bayer website at www.bayer.com. The company assumes no
liability whatsoever to update these forward-looking statements or to conform
them to future events or developments.
BAYER ANNUAL REPORT 2013
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First quarter of 2014
Bayer: Very successful start to 2014
Stockholders’ Newsletter
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Test lab for hightech materials
Fundamental research for new treatments
and healthier plants
English |
Bayer research 26 july 2014
German
research,
the Bayer scientific magazine
New canola variety
increases yields
Strong pods Light plane Special feature: ion channels
Cutting-edge global research for medical progress
EDITION 26 | July 2014
Networking for better healthcare
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